• Title/Summary/Keyword: Refractory

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Weekly Topotecan for Recurrent Small Cell Lung Cancer - a Retrospective Anatolian Medical Oncology Group Study

  • Altinbas, Mustafa;Kalender, Mehmet Emin;Oven, Basak;Sevinc, Alper;Karaca, Halit;Kaplan, M. Ali;Alici, Suleyman;Arpaci, Erkan;Yildiz, Ramazan;Uncu, Dogan;Camci, Celalettin;Gumus, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2909-2912
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    • 2012
  • Aim: To evaluate efficacy and tolerability of topotecan treatment for recurrent small cell lung carcinoma. Patients and Methods: A total of 62 patients were evaluated retrospectively. Statistical analysis was performed using GraphPad Instat (version 3.05). Results: DFifty five of patients (89%) were male and 7 (11%) were female. Median age was $56.7{\pm}9.3$ (34-75). Forty eight of patients (80%) were extensive stage (ES) at the time of diagnosis. Fifty of the patients (80.6 Medical Oncology Clinic) were given median 5.36 cycles of cisplatin-etoposide (2-8 cycles). Time to recurrence was $15.6{\pm}6.13$ weeks in patients with limited stage (LS) and $6.3{\pm}3.82$ weeks in extensive stage (ES) (p<0.0001). Overall survival was $14.0{\pm}6.08$ months in ES and $17.9{\pm}6.88$ months in LS. The difference between two groups was statistically meaningful (p=0.0447). The overall survival of the patients was $14.8{\pm}6.43$ months (4.5-40 months). In terms of survival, there was no difference between males and females (p=0.1171). In 17 (27%) patients who were refractory to topotecan or in whom progression occurred other chemotherapies were used. Conclusion: Small cell lung cancer is chemosensitive, but recurrences occur in short time. Other chemotherapy regimens are used in progression. Topotecan is one of them. Patients who were young and in whom recurrences occur late had given better response to topotecan. Because of the retrospective nature of the study, we couldn't reach the records exactly and consequently, rate and duration of response couldn't be calculated. In recurrent SCLC topotecan is one of the treatment choices. But both hematological and non hematological side effects should be taken into consideration.

Ultrasound Targeted Microbubble Destruction for Novel Dual Targeting of HSP72 and HSC70 in Prostate Cancer

  • Wang, Hang-Hui;Song, Yi-Xin;Bai, Min;Jin, Li-Fang;Gu, Ji-Ying;Su, Yi-Jin;Liu, Long;Jia, Chao;Du, Lian-Fang
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1285-1290
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    • 2014
  • The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

Assessment and Treatment of Depression in the Medically III (신체질환 환자들에서 우울증의 평가 및 치료)

  • Koh, Kyung-Bong
    • Korean Journal of Psychosomatic Medicine
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    • v.9 no.2
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    • pp.111-132
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    • 2001
  • Depression in the medically ill is a common clinical problem that primary physicians and psychiatric consultants encounter. Treatment of such patients begins with a careful evaluation of the patient's medical and psychiatric conditions. The assessment of depression in the medical patients requires a multidimensional approach. Psychological instruments are also used as a method of assessment in these patients. First of all, what the therapists have to do is to find and remove organic causes. Psychosoical treatment includes dealing with the patient's resistance and despondency relevant to physical diseases. For biological treatment, it is important to select appropriate antidepressants. Therapists should be familiar with the side effects of the antidepressants as well as the patient's primary depressive symptoms, pharmacokinetics and pharmacodynamics of the available agents. In addition, special attention should be paid to the potential for drug-illness and drug-drug interactions. Tricyclic antidepressants can be still effectively used for patients with pain disorder, although a variety of new antidepressants such as selective serotonin reuptake inhibitors (SSRI), bupropion and venlafaxine could have more benefits in depression of the medically ill. However, electroconvulsive therapy can be recommended for refractory cases of depression in patients with medical illness.

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Effects of applying nerve blocks to prevent postherpetic neuralgia in patients with acute herpes zoster: a systematic review and meta-analysis

  • Kim, Hyun Jung;Ahn, Hyeong Sik;Lee, Jae Young;Choi, Seong Soo;Cheong, Yu Seon;Kwon, Koo;Yoon, Syn Hae;Leem, Jeong Gill
    • The Korean Journal of Pain
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    • v.30 no.1
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    • pp.3-17
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    • 2017
  • Background: Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods: This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results: Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions: Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed.

Intracranial Pressure and Cerebral Blood Flow Monitoring after Bilateral Decompressive Craniectomy in Patients with Acute Massive Brain Swelling (급성 중증 뇌종창 환자의 양측성 감압개두술 후 뇌압 및 뇌혈류 측정)

  • Yoo, Do-Sung;Kim, Dal-Soo;Huh, Pil-Woo;Cho, Kyoung-Suck;Park, Chun-Kun;Kang, Joon-Ki
    • Journal of Korean Neurosurgical Society
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    • v.30 no.3
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    • pp.295-306
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    • 2001
  • Objectives : The management of massive brain swelling remains an unsolved problem in neurosurgical field. Despite newly developed medical and pharmacological therapy, the mortality and morbidity due to massive brain swelling remains high. According to many recent reports, surgical decompression with dura expansion is superior to medical management in patients with massive brain swelling. We performed surgical treatment on the first line of treatment, and followed medical management in case with refractory increased intracranial pressure(ICP). To show the quantitative effect of decompressive surgery on the intracranial pressure, we performed ventricular puncture and checked the ventricular ICP continuously during the decompressive surgery and postoperative period. Materials and Methods : Fifty-one patients with massive brain swelling, undergoing bilateral decompressive craniectomy with dura expansion, were studied in this study. In all patients, ventricular puncture was performed at Kocher's point on the opposite side of massive brain swelling. The ventricular pressure was monitored continuously, during the bilateral decompression procedures and postoperative period. Results : The initial ventricular ICP were varied from 13mmHg to 112mmHg. Immediately after the bilateral craniectomy, mean ventricular ICP decreased to $53.1{\pm}15.8%$ of the initial ICP(ranges from 5mmHg to 87mmHg). Dura opening decreased mean ICP by additional 36.7% and made the ventricular pressure $16.4{\pm}10.5%$ of the initial pressure (ranges from 0mmHg to 28mmHg). Postoperatively, ventricular pressure was lowered to $20.2{\pm}22.6%$(ranged from 0mmHg to 62.3mmHg) of the initial ICP. The ventricular ICP value during the first 24 hours after decompressive surgery was found to be an important prognostic factor. If ICP was over 35mmHg, the mortality was 100% instead of additional medical(barbiturate coma therapy and hypothermia) treatments. Conclusion : Bilateral decompression with dura expansion is considered an effective therapeutic modality in ICP control. To obtain favorable clinical outcome in patients with massive brain swelling, early decision making on surgical management and proper patient selection are mandatory.

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Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development

  • Cingeetham, Anuradha;Vuree, Sugunakar;Jiwatani, Sangeeta;Kagita, Sailaja;Dunna, Nageswara Rao;Meka, Phanni Bhushann;Gorre, Manjula;Annamaneni, Sandhya;Digumarti, Raghunadharao;Sinha, Sudha;Satti, Vishnupriya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2707-2712
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    • 2015
  • Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

Totally Laparoscopic Total Gastrectomy for Early Gastric Cancer: An Initial Experience (조기위암으로 진단된 환자에서의 전복강경하 위전절제술의 초기 경험)

  • Lee, Jeong-Seon;Lee, Han-Hong;Kim, Jin-Jo;Park, Seung-Man
    • Journal of Gastric Cancer
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    • v.10 no.1
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    • pp.26-33
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    • 2010
  • Purpose: We wanted to evaluate the technical feasibility and safety of totally laparoscopic total gastrectomy (TLTG) for treating early gastric cancer. Materials and Methods: The medical records of 11 consecutive patients who underwent TLTG after being diagnosed with early gastric cancer at Incheon St. Mary's Hospital, The Catholic University of Korea from February 2005 to September 2009 were retrospectively reviewed and their clinicopathologic characteristics and the surgical results wereinvestigated. Results: The mean operation time was $385.6{\pm}94.1$ minutes, the mean time for creating an intracorporeal anastomosis was $97.5{\pm}60.0$ minutes and the mean number of the harvested lymph nodes was $46.6{\pm}15.4$ The mean number of days after operation until starting a liquid diet was the $6.1{\pm}7.6^{th}$ postoperative day and the mean hospital stay after surgery was $14.2{\pm}11.9$ days. There was no case of open conversion, but there were 2 cases of intraoperative complication and 3 cases of postoperative complication. There was one case of postoperative mortality. The patient suffered from thrombocytopenia of an unknown cause, which was refractory to platelet transfusion, on $4^{th}$ postoperative day and the patient died of intraabdominal bleeding on the $6^{th}$ postoperative day. Conclusion: TLTG was a technically feasible and relatively safe procedure. However, a long time for creating the intracoproeal anastomosis and a long operation time are still problems to be solved.

An Analysis of the Existing Guidelines and Clinical Trials for the Development of the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) (위식도역류질환 한약제제 임상시험 가이드라인 개발을 위한 관련 국내 가이드라인 분석 및 기존 한약임상시험과의 비교)

  • Han, Ga-jin;Leem, Jung-tae;Kim, Jin-sung;Lee, Jun-hee
    • The Journal of Internal Korean Medicine
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    • v.37 no.1
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    • pp.90-108
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    • 2016
  • Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

Lack of Association of the NPAS2 Gene Ala394Thr Polymorphism (rs2305160:G>A) with Risk of Chronic Lymphocytic Leukemia

  • Rana, Sobia;Shahid, Adeela;Ullah, Hafeez;Mahmood, Saqib
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7169-7174
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    • 2014
  • Background: NPAS2 is a product of the circadian clock gene. It acts as a putative tumor suppressor by playing an important role in DNA damage responses, cell cycle control and apoptosis. Chronic lymphocytic leukemia (CLL) appears to be an apoptosis related disorder and alteration in the NPAS2 gene might therefore be directly involved in the etiology of CLL. Here, the Ala394Thr polymorphism (rs2305160:G>A) in the NPAS2 gene was genotyped and melatonin concentrations were measured in a total of seventy-four individuals, including thirty-seven CLL cases and an equal number of age- and sex-matched healthy controls in order to examine the effect of NPAS2 polymorphism and melatonin concentrations on CLL risk in a Pakistani population. Materials and Methods: Genotyping of rs2305160:G>A polymorphism at NPAS2 locus was carried out by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Melatonin concentrations were determined by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed using Statistical Package for Social Sciences software. Results: Our results demonstrated no association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with risk of CLL. Similarly, no association of rs2305160 with CLL was observed in either females or males after stratification of study population on a gender basis. Moreover, when the subjects with CLL were further stratified into shift-workers and non-shift-workers, no association of rs2305160 with CLL was seen in either case. However, significantly low serum melatonin levels were observed in CLL patients as compared to healthy subjects (p<0.05). Also, lower melatonin levels were seen in shift-workers as compared to non-shift-workers (p<0.05). There was no significant difference (p>0.05) in the melatonin levels across NPAS2 genotypes in all subjects, subjects with CLL who were either shift workers or non-shift-workers. General Linear Model (GLM) univariate analysis revealed no significant association (p>0.05) of the rs2305160 polymorphism of the NPAS2 gene with melatonin levels in any of the groups. Conclusions: While low melatonin levels and shift-work can be considered as one of the risk factors for CLL, the NPAS2 rs2305160 polymorphism does not appear to have any association with risk of CLL in our Pakistani population.

Radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma: dose-volumetric analysis and its clinical implications

  • Lim, Hyeon Woo;Kim, Tae Hyun;Choi, Il Ju;Kim, Chan Gyoo;Lee, Jong Yeul;Cho, Soo Jeong;Eom, Hyeon Seok;Moon, Sung Ho;Kim, Dae Yong
    • Radiation Oncology Journal
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    • v.34 no.3
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    • pp.193-201
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    • 2016
  • Purpose: To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. Materials and Methods: Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. Results: All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, $D_{max}$ and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and $D_{mean}$ and V15 for right kidney and $D_{mean}$ for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). Conclusion: Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.