• Title/Summary/Keyword: Cis-platinum

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Multi-Nuclear NMR Investigation of Nickel(II), Palladium(II), Platinum(II) and Ruthenium(II) Complexes of an Asymmetrical Ditertiary Phosphine

  • Raj, Joe Gerald Jesu;Pathak, Devendra Deo;Kapoor, Pramesh N.
    • Journal of the Korean Chemical Society
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    • v.57 no.6
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    • pp.726-730
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    • 2013
  • Complexes synthesized by reacting alkyl and aryl phosphines with different transition metals are of great interest due to their catalytic properties. Many of the phosphine complexes are soluble in polar solvents as a result they find applications in homogeneous catalysis. In our present work we report, four transition metal complexes of Ni(II), Pd(II), Pt(II) and Ru(II) with an asymmetrical ditertiaryphosphine ligand. The synthesized ligand bears a less electronegative substituent such as methyl group on the aromatic nucleus hence makes it a strong ${\sigma}$-donor to form stable complexes and thus could effectively used in catalytic reactions. The complexes have been completely characterized by elemental analyses, FTIR, $^1HNMR$, $^{31}PNMR$ and FAB Mass Spectrometry methods. Based on the spectroscopic evidences it has been confirmed that Ni(II), Pd(II) and Pt(II) complexes with the ditertiaryphosphine ligand showed cis whereas the Ru(II) complex showed trans geometry in their molecular structure.

GSTP1, ERCC1 and ERCC2 Polymorphisms, Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

  • Li, Hui-Yan;Ge, Xin;Huang, Guang-Ming;Li, Kai-Yu;Zhao, Jing-Quan;Yu, Xi-Miao;Bi, Wen-Si;Wang, Yu-Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.7
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    • pp.3465-3469
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    • 2012
  • Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients.

Early Activation of Apoptosis and Caspase-independent Cell Death Plays an Important Role in Mediating the Cytotoxic and Genotoxic Effects of WP 631 in Ovarian Cancer Cells

  • Gajek, Arkadiusz;Denel-Bobrowska, Marta;Rogalska, Aneta;Bukowska, Barbara;Maszewski, Janusz;Marczak, Agnieszka
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8503-8512
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    • 2016
  • The purpose of this study was to provide a detailed explanation of the mechanism of bisanthracycline, WP 631 in comparison to doxorubicin (DOX), a first generation anthracycline, currently the most widely used pharmaceutical in clinical oncology. Experiments were performed in SKOV-3 ovarian cancer cells which are otherwise resistant to standard drugs such as cis-platinum and adriamycin. As attention was focused on the ability of WP 631 to induce apoptosis, this was examined using a double staining method with Annexin V and propidium iodide probes, with measurement of the level of intracellular calcium ions and cytosolic cytochrome c. The western blotting technique was performed to confirm PARP cleavage. We also investigated the involvement of caspase activation and DNA degradation (comet assay and immunocytochemical detection of phosphorylated H2AX histones) in the development of apoptotic events. WP 631 demonstrated significantly higher effectiveness as a pro-apoptotic drug than DOX. This was evident in the higher levels of markers of apoptosis, such as the externalization of phosphatidylserine and the elevated level of cytochrome c. An extension of incubation time led to an increase in intracellular calcium levels after treatment with DOX. Lower changes in the calcium content were associated with the influence of WP 631. DOX led to the activation of all tested caspases, 8, 9 and 3, whereas WP 631 only induced an increase in caspase 8 activity after 24h of treatment and consequently led to the cleavage of PARP. The lack of active caspase 3 had no outcome on the single and double-stranded DNA breaks. The obtained results show that WP 631 was considerably more genotoxic towards the investigated cell line than DOX. This effect was especially visible after longer times of incubation. The above detailed studies indicate that WP 631 generates early apoptosis and cell death independent of caspase-3, detected at relatively late time points. The observed differences in the mechanisms of the action of WP631 and DOX suggest that this bisanthracycline can be an effective alternative in ovarian cancer treatment.

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

  • Wu, Xue-Yan;Huang, Xin-En;You, Shan-Xi;Lu, Yan-Yan;Cao, Jie;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2019-2022
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    • 2013
  • Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

CAD for extension of sweet spot of the tennis racket (테니스라켓의 안정타점 영역확장을 위한 CAD화에 관한 연구)

  • Oh, Jae-Eung;Park, Ho;Yum, Sung-Ha
    • 제어로봇시스템학회:학술대회논문집
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    • 1986.10a
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    • pp.607-612
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    • 1986
  • 최근 테니스의 저변인구가 크게 증가함에 따라 테니스 라켓의 제작기술도 상당한 수준에 이르렀고 설계제작의 자동화에 의해서 양질의 제품이 시판되고 있다. 그러나 라켓에 볼이 임팩트될때 생기는 진동으로 야기되는 테니스 엘보우 등, 해결해야 할 문제들이 아직도 남아 있다. 이와같이 테니스 라켓의 정적인 강도 뿐만아니라 동적인 특성도 중요한 관심의 대상이 되어감에 따라 볼 컨트롤을 용이하게 한다거나, 안정타점영역(Sweet Spot)의 확장과 그립부의 진동등에 의해서 발생하는 엘보우 현상을 방지하기 위해 여러가지 연구가 수행되어 왔다. 특히, 다차원 스펙트럼해석 및 모우드 해석법에의해 그립부에 미치는 진동원의 동정과 라켓의 동적거동에 대해서 연구되었고, 라켓의 재질변경과 그립부의 구조변경에 의한 안정타점영역에 영향을 미치는 모우드 파라미터(Modal Parameter)의 추정에 관한 연구도 수행되었다. 이러한 연구들은 결국 안정타점영역을 확장시키거나 테니스 엘보우를 방지하기 위한 것으로서 이러한 목적을 달성하기위해 테니스 라켓의 진동 모우드에 관계되는 파라미터들을 찾아서 그 모우드 파라미터의 변화에 따르느 진동 모우드의 거동에 대해서 연구할 필요가 있다. 본 논문에서는 실험적인 모우드 해석법을 실제 테니스 라켓에 적용하여 모우드 파라미터들을 구한 다음 그 파라미터의 변화에 따르는 안정타점영역의 변화를 컴퓨터 시뮬레이션을 통해서 예측하였다. 또한 안정타점영역을 넓히고 라켓의 동특성을 개선시킬 수 있는 모우드 파라미터를 찾아서 테니스 라켓의 설계, 제작 단계에 정보를 제공하는 CAD(Computer Aided Design)에 좋은 자료를 얻고자 한다. 있으나 파도에 의한 영향이 가장 크므로 본 논문에서는 파도에 의한 영향만을 고려하였다. 파도는 쌍동선에 외란으로 작용하며 측정할 수 없는 양이므로 PID, LQ 제어에서는 제어모델에 포함되지 않지만 LQG 제어에서는 제어모델에 포함된다. LQG 제어의 경우 제어모델에 파도를 백색잡음으로 가정하고 제어기를 구성한 것 (LQG1)과 2차의 쉐이핑필터(shaping filter)를 사용하여 구성한 것(LQG2)으로 나누었다.져 한다.) 식도 이물에 의한, 또는 식도경술에 의한 합병증이 초래한 경우는 식도점막열상 1례 (1.8 %), 식도 천공 1례 (1.8 %) 였으며, 기도이물에 의한, 또는 기관지경술에 의한 합병증이 초래한 경우는 무기폐 2례 (11.1 %), 폐렴 3례 (16.7 %)로 나타났다.5예에서 소실되었다. 5 ) 청각심리검사 (Psychoacoustic evaluation)에서 폴립은 술전에 Grade 1∼2의 사성이 있었던 11예중 술후 10예에서 Grade 0로 되었으며 Grade 1∼2의 사성이 있었던 3예의 결절에서도 모두 Grade 0로 정상화되었다.>치를 측정한 결과 투여전과 차이가 없었다. 7) 이상의 결과로 볼때 Cis-platinum 사용으로 인한 이중독증은 신장기능이 정상일때는 충분한 hydration으로써 예방이 가능하며 동시에 금기로 알려져왔던 감음성난청이 있는 두경부악성종양환자에서도 세심한 주의하에 적절히 사용한다면 좋은 결과를 얻을 수 있을 것으로 사려된다.은 결과를 얻었기에 문헌고찰과 함께 보고하는 바이다. 1) 이관폐쇄술후 18시간에 최초로 삼출액이 확인되었으며 그 이후는 전실험군에서 삼출성중이염이 유발되다. 2

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Evaluation of the Effect of Pentoxifylline on Cisplatin-Induced Testicular Toxicity in Rats

  • Fallahzadeh, Ali Reza;Rezaei, Zohreh;Rahimi, Hamid Reza;Barmak, Mehrazd Jafari;Sadeghi, Hossein;Mehrabi, Sadrollah;Rabani, Seyed Mohammadreza;Kashani, Iraj Ragerdi;Barati, Vahid;Mahmoudi, Reza
    • Toxicological Research
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    • v.33 no.3
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    • pp.255-263
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    • 2017
  • Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the $14^{th}$ day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

Clinical Study on Laryngo - Microscopic Surgery For Vocal Nodules and Polyps (후두결절 및 폴립의 후두미세 수술에 관한 임상연구)

  • 문영일
    • Proceedings of the KOR-BRONCHOESO Conference
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    • 1983.05a
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    • pp.11.2-11
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    • 1983
  • Vocal nodules and polyps are much more frequent in singers, public speakers, teachers and actors. Voice trauma and voice misuse, at times associated with mild inflammatory reaction, appear to be important in their etiology. It is generally agreed that vocal cord nodules and polyps are inflammatory in nature and they arise in the subepithelial layer of loose connective tissue of the vocal cord. Since the junction of anterior and middle thirds of the membranous cord and has the greatest amplitude of vibration. This is the site of predilection for vocal cord nodules. The author performed laryngomicrosurgery for 70 cases of vocal nodules and polyps at Ewha Womans University Hospital during the period of 5 years. The result obtained were as follows ; 1) Surgical excision is not necessarily the best approach because vocal nodules in the early stages will resolve with the simplest voice therapy. 2) In children, surgery is rarely indicated because most nodules in children regress during adolescence. 3) For patients who use their voices professionally, voice therapy is indicated for three months. 4) If after three month of conservative treatment the cord lesion does not improve and the patient it still dissatisfied with his voice, laryngomicrosurgery can then be considered. 5) The small cuffed endotracheal tube in the interarytenoid space helps to keep the cords immobile and in an abducted position. 6) Removal of the nodule shoule be started by gentle retraction posteriorly and as soon as a tear appears anterior to the nodule. 7) On occasion it is preferable to start the dissection with a siccle knife while the nodule is held on the stretch. 8) Voice rest should be maintained for a week following which the free edges of the cords are usually healed.

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Induction Chemotherapy and Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (국소 진행된 비소세포성 폐암에서 유도 화학요법 및 방사선치료)

  • Yun, Sang-Mo;Kim, Jae-Cheol;Park, In-Kyu
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.195-202
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    • 1999
  • Purpose : We peformed this study to evaluate the prognostic factors and the effect of induction chemotherapy in locally advanced non-small cell lung cancer (NSCLC). Materials and Methods : A retrospective analysis was done for 130 patients with locally advanced NSCLC treated with curative radiotherapy alone or induction chemo-radiotherapy from January 1986 to October 1996. Eighty-five patients were treated with radiotherapy alone, forty-five with induction chemotherapy and radiotherapy. Age, sex, performance status, histopathologic type, and stage were evenly distributed in both groups. The patients were treated with 6 MV or 10 MV X-ray. Conventional fractionation with daily fraction size 1$.8\~2.0$ Gy was done. Of the patients, 129 patients received total dose above 59.6 Gy ($56\~66$ Gy, median 60 Gy). Induction chemotherapy regimen were CAP (Cyclo-phosphamide, Adriamycin, Cisplatin) in 6 patients, MVP (Mitomycin, Vinblastine, Cisplatin) in 9 patients, MIC (Mitomycin, Ifosfamide Cisplatin) in 13 patients, and EP (Etoposide, Cisplatin) in 17 patients. Chemotherapy was done in $2\~5$ cycles (median 2). Results : Overall 1-, 2-, and 3-year survival rate (YSR) for all patients were $41.5\%,{\;}13.7\%,{\;}and{\;}7\%$, respectively (median survival time 11 months). According to treatment modality, median survival time, overall 1-, 2-, and 3-YSR were 9 months, $32.9\%,{\;}10.\5%,{\;}6\%$ for radiotherapy alone group, and 14 months, $57.8\%,{\;}20\%,{\;}7.6\%$ for induction chemotherapy group, respectively (f=0.0005). Complete response (CR) to overall treatments was $25\%$ (21/84) in radiotherapy alone and $40.5\%$ (17/42) in induction chemotherapy group (p=0.09). The Prognostic factors affecting overall survival were hemoglobin level (p=0.04), NSE (neuron-specific enolase) level (p=0.004), and respense to overall treatment(p=0.004). According to treatment modalities, NSE (neuron-specific enolase) (p=0.006) and response to overall treatment (p=0.003) were associated with overall survival in radiotherapy alone group, and response to overall treatment (p=0.007) in induction chemotherapy group. The failure Pattern analysis revealed no significant difference between treatment modalities. But, in patients with CR to overall treatment, distant metastasis were found in 11/19 patients with radiotherapy alone, and 3/13 patients with induction chemotherapy and radiotherapy (p=0.07). Locoregional failure patterns were not different between two groups (10/19 vs 6/13). Conclusion : Induction chemotherapy and radiotherapy achieved increased 2YSR compared to radiotherapy alone, At least in CR patients, there was decreased tendency in distant metastasis with induction chemotherapy. But, locoregional failures and long-term survival were not improved. Thus, there is need of more effort to increasing local control and further decreasing distant metastasis.

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The Role of Intraluminal Brachytherapy in Management of Esophageal Cancer (식도암 치료에 있어 관내근접치료의 역할)

  • Lee Chang Geol;Suh Chang Ok;Kim Gwi Eon;Chu Sung Sil;Chung Eun Ji;Kim Woo Cheol
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.331-338
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    • 1995
  • Purpose : To evaluate our clinical experience with the combination of teletherapy and intraluminal brachytherapy in patients with unresectable or inoperable esophageal cancers. Materials and Methods : From Nov 1989 to Mar 1993, twenty patients with esophageal cancer were treated with radical radiotherapy and intraluminal brachytherapy at Yonsei Cancer Center. All patients had squamous histolgy and stage distribution was as follows: stage II, 4($20{\%}$)patients; III, 15 ($75{\%}$)patients; IV, 1($5{\%}$)patients. A dose of S-12Gy/1-3weeks with intraluminal brachytherapy (3-5Gy/fraction) to 5mm from the outside of the esophageal tube using high dose rate Iridium-192 remotely afterloading brachytherapy machine was given 2 weeks after a total dose of 59-64Gy with external radiotherapy. Induction chemotherapy using cisplatin and 5-FU was performed in 13 patients with median 3 cycles(1-6 cycles), Response rate, local control rate, survival and complications were analysed retrospectively. Results : Two-year overall survival rate and median survival were $15.8{\%}$ and 13.5 months. Response rates were as follows complete remission(CR) 5($25{\%}$): partial remission a(PRa) 7($35{\%}$): partial remission b(PRb) 7($35{\%}$), no response(NR) 1($5{\%}$). Patterns of failure were as follows; local failure 13($65{\%}$), local and distant failure 3($15{\%}$), distant failure 0($0{\%}$). Ultimate local control rate was $20{\%}$. Treatment related complications included esophageal ulcer in two patients and esophageal stricture in one. Conclusion : Though poor local conrol rate, median survival was improved as compared with previous results of radiation therapy alone(8months) and chemoradiation combined treatment(11 months) in Yonsei Cancer Center High-dose-rate intraluminal brachytherapy following external irradiation is an effective treatment modality with acceptable toxicity in esophageal cancer.

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