• Title/Summary/Keyword: induction chemotherapy

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Potent Anticancer Effects of Lentivirus Encoding a Drosophila Melanogaster Deoxyribonucleoside Kinase Mutant Combined with Brivudine

  • Zhang, Nian-Qu;Zhao, Lei;Ma, Shuai;Gu, Ming;Zheng, Xin-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2121-2127
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    • 2012
  • Objective: Deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) mutants have been reported to exert suicide gene effects in combined gene/chemotherapy of cancer. Here, we aimed to further evaluate the capacity of the mutanted enzyme and its potential for inhibiting cancer cell growth. Methods: We altered the sequence of the last 10 amino acids of Dm-dNK to perform site-directed mutagenesis and constructed active site mutanted Dm-dNK (Dm-dNKmut), RT-PCR and western bloting studies were used to reveal the expression of lentivirus mediated Dm-dNKmut in a breast cancer cell line (Bcap37), a gastric cancer cell line (SGC7901) and a colorectal cancer cell line (CCL187). [3H]-labeled substrates were used for enzyme activity assays, cell cytotoxicity was assessed by MTT assays, cell proliferation using a hemocytometer and apoptosis induction by thenannexin-V-FITC labeled FACS method. In vivo, an animal study was set out in which BALB/C nude mice bearing tumors were treated with lentivirus mediated expression of Dm-dNKmut with the pyrimidine nucleoside analog brivudine (BVDU, (E)-5-(2-bromovinyl)-(2-deoxyuridine). Results: The Dm-dNKmut could be stably expressed in the cancer cell lines and retained its enzymatic activity. Moreover, the cells expressing Dm-dNKmut exhibited increased sensitivity in combination with BVDU, with induction of apoptosis in vitro and in vivo. Conclusion: These findings underlined the importance of BVDU phosphorylated by Dm-dNKmut in transduced cancer cells and the potential role of Dm-dNKmut as a suicide gene, thus providing the basis for future intensive research for cancer therapy.

Heat Shock Induces Necrosis in Cisplatin-resistant Gastric Cancer Cells through Suppressing JNK1/2 Activation and HSP27 Induction (시스플라틴 내성세포주에서 열충격에 의한 세포사멸에 관한 연구)

  • Lim, Sung-Chul;Choi, Cheol-Hee;Han, Song-Iy
    • Journal of Life Science
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    • v.19 no.12
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    • pp.1705-1711
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    • 2009
  • Carcinoma cells that had acquired resistance to a chemotherapeutic drug often show cross-resistance to various other cytotoxic drugs. In the present study, we explored the effect of heat shock in cisplatin-resistant gastric cancer cells SNU601/Cis2 to figure out the efficacy of hyperthermia in drug-resistant carcinoma. While SNU601/WT cells showed a high-sensitivity response to heat shock by dying through apoptosis, SNU601/Cis2 cells were considerably resistant to mild heat shock, but died by necrosis upon treatment with harsh heat shock. The occurrence of necrosis in SNU601/Cis2 cells was linked to the suppression of both JNK1/2 activation and HSP27 induction in response to heat shock. Since necrosis is closely associated with tumor malignancy and poor prognosis through inflammatory responses, our result suggests that hyperthermic treatment should be carefully applied when it is combined with chemotherapy.

Correlation Between Expression of ER, PR and C-erbB-2 Protein as Histologic Grade of Breast Cancer (유방암의 조직학적 악성도에 따른 에스트로겐 수용체(ER)와 프로게스테론 수용체(PR), 그리고 C-erbB-2 종양단백질 발현과의 상관관계)

  • Han, Kyung Hee;Kim, Tai Jeon
    • Korean Journal of Clinical Laboratory Science
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    • v.36 no.2
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    • pp.185-192
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    • 2004
  • Overexpressions of the estrogen receptors(ER), progesterone receptors(PR) and C-erbB-2 protein are important determiners of the response to chemotherapy in the breast cancer. For detecting ER, PR and C-erbB-2, immunohistochemistry are currently regarded as standard method. The purposes of this study compared to histologic grade and expression of the ER, PR and C-erbB-2 in breast cancer. We examined overexpression of ER, PR and C-erbB-2 protein in 84 breast carcinomas by using immunohistochemical stains. The following results were obtained. For histologic grade, 10 cases(11.9%) showed carcinoma in situ, 16 cases(19%) showed grade I, 36 cases (42.9%) showed grade II, and 22 cases(26.2%) showed grade III among the 84 test samples. The average positive rate ER and PR was 63%, 46% showed carcinoma in situ, 80%, 60% showed grade I, 64%, 41% showed grade II, 34%, 23% showed grade III, respectively. The induction of PR increased when induction of ER increased, thus showing significant relationship(p<0.05). The expression of C-erbB-2 protein was 9 cases(10.7%) in one positive(1+), 9 cases(10.7%) in two positive(2+), and 9 cases(10.7%) in three positive(3+). C-erbB-2 protein expression showed no statistical significance. In conclusion, ER and PR positive rates were inversely associated with histologic grades significantly(p<0.05). C-erbB-2 showed no significant difference with histologic grade. However ER, PR and C-erbB-2 showed significant relationship with each other(p<0.05). Therefore, these findings might be an important prognostic factor and might be arranged as a regular pathological examination in cases of breast cancer.

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Capsaicin Ameliorates Cisplatin-Induced Renal Injury through Induction of Heme Oxygenase-1

  • Jung, Sung-Hyun;Kim, Hyung-Jin;Oh, Gi-Su;Shen, AiHua;Lee, Subin;Choe, Seong-Kyu;Park, Raekil;So, Hong-Seob
    • Molecules and Cells
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    • v.37 no.3
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    • pp.234-240
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    • 2014
  • Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

Effect of Prophylactic Cranial Irradiation in Acute Lymphoblastic Leukemia in Children (소아 급성 임파구성 백혈병에서 예방적 전뇌 방사선조사의 효과)

  • Kim Il Han;Choi Doo Ho;Kim Jong Hoon;Ha Sung Whan;Park Charn Il;Ahn Hyo Seop
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.269-277
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    • 1989
  • CNS prophylaxis with 18 or 24 Gy cranial irradiation plus intrathecal methotrexate was given to 134 childhood acute lymphoblastic leukemia patients who had got bone marrow remission (M1) after remission induction chemotherapy from August 1979 to December 1986. The rate of initial total CNS relapse was 14.2% (19/134), the rate of isolated CNS relapse was 5.2% (7/134), and the rate of CNS relapse concomittantly combined with bone marrow relapse or testicular relapse was 9% (12/134). Male sex or older age was accociated with higher CNS relapes and the initial peripheral leukocyte count over 50,000/ul had higher relapse rate. Relapse with radiation dose of 18Gy was somewhat lower than that with 24Gy. Within 4 years after CNS prophylaxis occurred 89% of the total CNS relapses, 100% of the isolated CNS relapses, and 83% of the combined CNS relapses. Adjusted to exposed cases to risk of CNS relapse, the total CNS relapse rate was 11.9% during maintenance chemotherapy and 4.9% after maintenance chemotherapy.

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Cloning and characterization of polyA- RNA transcripts encoded by activated B1-like retrotransposons in mouse erythroleukemia MEL cells exposed to methylation inhibitors

  • Tezias, Sotirios S.;Tsiftsoglou, Asterios S.;Amanatiadou, Elsa P.;Vizirianakis, Ioannis S.
    • BMB Reports
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    • v.45 no.2
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    • pp.126-131
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    • 2012
  • We have previously identified a DNA silent region located downstream of the 3'-end of the ${\beta}^{major}$ globin gene (designated B1-559) that contains a B1 retrotransposon, consensus binding sites for erythroid specific transcription factors and shares the capacity to act as promoter in hematopoietic cells interacting with ${\beta}$-globin gene LCR sequences in vitro. In this study, we have cloned four new non-polyA RNA transcripts being detected upon blockade of murine erythroleukemia (MEL) cell differentiation to erythroid maturation by methylation inhibitors and demonstrated that two of them share high structural homology with sequences of B1 element found within the B1-559 region. Although it is not clear yet whether and how these RNAs interfere with induction of erythroid maturation, these data provide evidence for the first time showing that methylation inhibitors can activate silent repetitive DNA sequences in MEL cells and may have implications in cancer chemotherapy using demethylating drugs as antineoplastic agents.

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

  • Manapov, Farkhad;Roengvoraphoj, Olarn;Li, Minglun;Eze, Chukwuka
    • Radiation Oncology Journal
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    • v.35 no.2
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    • pp.180-184
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    • 2017
  • Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second $[FEV1]{\leq}1L$) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function ($FEV1{\leq}1L$).

Purification of Lovastatin from Aspergillus terreus (KM017963) and Evaluation of its Anticancer and Antioxidant Properties

  • Bhargavi, SD;Praveen, VK;Marium, Salah;Sreepriya, M;Savitha, J
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.8
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    • pp.3797-3803
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    • 2016
  • Cervical cancer is the second most common malignancy in women worldwide and thus one of the leading causes of mortality in women. Lovastatin, a non polar, anticholesterol drug has previously been reported to exert antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties with a human cervical cancer cell line (HeLa). Growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cells were investigated by determining its influence on cell numbers, mitochondrial membrane potential (MMP), DNA fragmentation and antioxidant properties in terms of hydroxy radical scavenging effects as well as levels of total reduced glutathione. Cell cycle analysis by flow cytometry (propidium iodide staining) confirmed induction of apoptotic cell death and revealed cell cycle arrest in the G0/G1 phase. Results of the study give leads for the anticancer effects of lovastatin and its potential usefulness in the chemotherapy of cervical cancer.

Walk-Up flap for Reconstruction of Oral and Maxillofacial defects (Walk-Up flap을 이용한 악안면 영역의 결손부 재건)

  • Shin, Sang-Hun;Park, Sung-Jin;Lee, Kwang-Ho;Lee, Sung-Keun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.22 no.2
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    • pp.249-253
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    • 2000
  • Oral and Maxillofacial defects is produced by trauma or cancer surgery. This defects have been shown functional loss such as mastication, swallowing, speech and psychosocial esthetic problem. Oral and Maxillofacial defects is reconstructed by the use of many flaps. However although previous flap surgery was done, additional soft tissue defects can be still remained. In this case, Walk-Up flap that is introduced by Marx RE in 1990 is recommended for successful reconstruction. We report Walk-Up flap for reconstruction of remained soft tissue defects of tongue S.C.C. After induction chemotherapy, tongue S.C.C. is excised surgically and reconstructed by use of PMMC flap. Post-op infection results in surrounding soft tissue defect with oro-facial fistula. We have experienced a case of Walk-up flap by use of PMMC flap for reconstruction with satisfactory result, so we report it with literature reviews.

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Mixture of Wild Panax Ginseng and Red-Mold Rice Extracts Activates Macrophages through Protection of Cell Regression and Cytokine Expression in Methotrexate-Treated RAW264.7 Cells

  • Shin, Heung-Mook
    • The Journal of Korean Medicine
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    • v.30 no.6
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    • pp.69-79
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    • 2009
  • Objective: In this study, the immunomodulatory activity of a mixture of wild Panax ginseng and red-mold rice extracts (MPR) on RAW 264.7 macrophage cells in the presence and absence of methotrexate (MTX), an anti-cancer drug, was investigated. Methods and Results: In the cell viability, MPR showed a significant cell proliferation and inhibited cell regression by red-mold rice (RMR) alone or MTX alone. MPR induced moderate increase in nitric oxide (NO) production. NO production and inducible nitric oxide synthase (iNOS) mRNA expression by LPS decreased after MPR treatment. In addition, MPR slightly induced COX-2 mRNA expression, but it did not affect the expression of COX-2 mRNA by LPS treatment. In RT-PCR analyses, MPR induced IL-$1{\alpha}$, IL-$1{\beta}$, IL-6, and TNF-$\alpha$ mRNA expression, but had no effect on IL-10 and TGF-$\beta$, regardless of MTX treatment. Furthermore, MPR did not interfere with the cytotoxicity of MTX against MCF-7 human breast carcinoma cells. Conclusions: MPR is efficacious in protecting against MTX-induced cell regression as a result of macrophage activation, resulting in induction of cytokine expression, implying that MPR could be considered an adjuvant in MTX-chemotherapy.

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