• Title/Summary/Keyword: Second line therapy

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RNA Interference-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth, Induces Apoptosis, and Increases the Chemosensitivity to 5-Fluorouracil in Renal Cancer Caki-1 Cells

  • Wang, Peng;Yin, Bo;Shan, Liping;Zhang, Hui;Cui, Jun;Zhang, Mo;Song, Yongsheng
    • Molecules and Cells
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    • v.37 no.12
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    • pp.857-864
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    • 2014
  • Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.

Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE)

  • Lee, Kwan-Ho;Lee, Kye-Young;Jeon, Young-June;Jung, Maan-Hong;Son, Choonhee;Lee, Min-Ki;Ryu, Jeong-Seon;Yang, Sei-Hoon;Lee, Jae-Cheol;Kim, Young-Chul;Kim, Sun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.6
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    • pp.303-311
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    • 2012
  • Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

  • Kang, Sun Kyoung;Bae, Hyun Joo;Kwon, Woo Sun;Che, Jingmin;Kim, Tae Soo;Chung, Hyun Cheol;Rha, Sun Young
    • Genomics & Informatics
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    • v.18 no.4
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    • pp.37.1-37.11
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    • 2020
  • BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Cisplatin-Based Therapy for the Treatment of Elderly Patients with Non-Small-Cell Lung Cancer: a Retrospective Analysis of a Single Institution

  • Inal, Ali;Kaplan, M. Ali;Kucukoner, Mehmet;Urakcl, Zuhat;Karakus, Abdullah;Islkdogan, Abdurrahman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.1837-1840
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    • 2012
  • Background: In spite of the fact that platinum-based doublets are considered the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC), no elderly-specific platinum based prospective phase III regimen has been explored. The aim of this retrospective singlecenter study was to evaluate the efficacy and side effects of cisplatin-based therapy specifically for the elderly. Methods: Patients receiving platinum-based treatment were divided into three groups. In the first group (GC), Gemcitabine was administrated at 1000 $mg/m^2$ on days 1, 8 and cisplatin was added at 75 $mg/m^2$ on day 1. In the second group (DC), 75 $mg/m^2$ docetaxel and cisplatin were administered on day 1. The third group (PC) received 175 mg of paclitaxel and 75 mg of cisplatin on day 1. These treatments were repeated every three weeks. Result: GC arm had 36, the DC arm 42 and the PC arm 29 patients. Grade III-IV thrombocytopenia was higher in the GC arm (21.2% received GC, 2.8% received DC, and 3.8% received PC), while sensory neuropathy was lower in patients with GC arm (3.0%, 22.2%, and 23.1% received GC, DC and PC, respectively). There were no statistically significant difference in the response rates among the three groups (p>0.05). The median Progression-free survival (PFS) was 5.0 months and the median Overall survival (OS) in each group was 7.1, 7.4 and 7.1 months, respectively (p>0.05). Conclusion: The response rate, median PFS and OS were similar among the three treatment arms. Grade III-IV thrombocytopenia was higher in the GC arm, while the GC regimen was more favorable than the other cisplatin-based treatmetns with regard to sensory neuropathy.

Reliability study of the Pectoralis Minor Muscle Thickness Measurement using Rehabilitative Ultrasound Imaging

  • Lim, Ji Young;Lee, Se-Yeong;Jung, Seung-Hwa;Park, Dae-Sung
    • Journal of the Korean Society of Physical Medicine
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    • v.16 no.2
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    • pp.45-52
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    • 2021
  • PURPOSE: This study examined the imaging procedure of pectoralis minor muscle thickness and assessed the intra- and inter-rater reliability of the muscle thickness measured by two raters using rehabilitative ultrasound imaging (RUSI) in healthy individuals. METHODS: Fifteen participants (aged 21 - 28, seven females, and eight males) were involved in the study. The primary rater palpated the coracoid process and the fourth rib, defined as the width of the index finger lateral to the sternum to avoid breast tissues, and lined the two landmarks. The second examiner checked 1 / 3 (1st point) and 1 / 2 (2nd point) of the line length as measurement points. The two raters obtained right side muscle images of the participants at a standardized sitting position using RUSI with a 7.5 MHz linear transducer at 40mm depth. For intra-rater reliability, the principal rater took three images per point and tried to take one more with an interval. For the inter-rater reliability, the other rater performed the same tasks as the principal rater on the same day. The reliability was analyzed using the intra-class correlation coefficient (ICC), the standard error of the measurement (SEM), and Bland and Altman plots. RESULTS: The reliability at all points was excellent for the same rater (ICC3,1 = .973 - .978, SEM = .042 - .046), and between raters (ICC2,1 = .939 - .959, SEM = .059 - .097). CONCLUSION: These findings show that the RUSI could be reliable for examining the pectoralis minor muscle thickness in healthy individuals at all measurement sites.

Improvement of patient's quality of life by improving patient's set-up line in radiotherapy (방사선 치료 시 환자 Set-up Line 개선을 통한 암환자 삶의 질 만족도 향상)

  • Choi, Jin Hyuk;Ahn, Woo Sang;Lee, Woo Seok;Kim, Dae Yong
    • The Journal of Korean Society for Radiation Therapy
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    • v.30 no.1_2
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    • pp.185-189
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    • 2018
  • Purpose : We evaluated the quality of life satisfaction of patients with radiation therapy while maintaining the set-up line. Materials and Methods : We retrospectively reviewed 60 patients who visited our clinic in January, 2018. The most common complaint was the inconvenience of not being able to wash during treatment (64 %), and a surgical tape was placed on the Set-up Line to help patients wash during the treatment period. A total of 50 patients who underwent surgical tape were evaluated on a 5-point scale (1 point was very unsatisfactory, 2 points were unsatisfactory, 3 points were average, 4 points were satisfied, 5 points were very satisfied). Forty patients out of 50 responded to the first treatment, and 10 patients underwent treatment. Results : In the first survey, 68 % of the patients and 32 % of the males were aged 34 %, 50~60 % and 38 %, respectively. Treatment areas were breast (57 %), chest (13 %), pelvis (10 %). The results of the second questionnaire after applying the surgical tape showed that 25 of the 40 patients and 15 of the male patients were treated. The treatment area was 22 breast and 18 pelvic areas. In the satisfaction of the 5-point scale, 5 to 15 points were satisfied with 1-3 points, and 4-5 points with 35 points (1 point 2 points, 2 points 2 points, 3 point 1 points, 4 point points 17 point points, % And 43 %, respectively. The results of the questionnaire survey of patients who were applied during the treatment showed that 9 out of 10 women and 1 male were treated. The treatment area was 8 breast and 2 pelvic areas. One point was satisfied with one point, and five points with nine points were satisfied with 90 %. Conclusions : The importance of improving the quality of life of patients with cancer is also important. After applying the surgical tape, 88 % of the patients who started the treatment and 90 % of the patients who applied during the treatment were satisfied. Particularly, patients who applied during treatment showed higher satisfaction. If this is not possible for all patients, selective application to patients with discomfort will be helpful in improving the quality of life of cancer patients.

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Use of ALLGIO Probe Assays for Detection of HBV Resistance to Adefovir in Patients with Chronic Hepatitis B, Kerman, Iran

  • Afshar, Reza Malekpour;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5463-5467
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    • 2012
  • Hepatitis B virus (HBV) infection is contagious with transmissiobn vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. To evaluate the resistance to adefovir (ADV) therapy in patients with chronic hepatitis B infection, a study was conducted on 70 patients (63 males and 7 females), who had received in first line lamivudine and second line adefovir. All were tested for the presence of hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), serum alanine amino transferase (ALT) level and HBV DNA load before and after treatment with ADV. In all samples, resistance to lamivudine and ADV was tested with real time PCR. Among seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to LAM and 8 (11.4%) were resistant to ADV. Only one patient was negative for the presence of HBS-Ag (5.6%) and two were negative for HBe-Ag (11.1%). In this study we used a new method (ALLGIO probe assay) that has high sensitivity in detection of adefovir resistance mutants, which we recommend to other researchers. Mutant strains of the YMDD motif of HBV polymerase can be found in some patients under treatment with lamivudine and ADV. ADV has been demonstrated to be efficient in patients with lamivudine resistant HBV.

A Case of Intestinal Tuberculosis Complicated with Pulmonary Tuberculosis in a Young Aldolescent with Cerebral Palsy (뇌성마비 소아에서 진단된 폐결핵에 병발된 결핵성 장염 1례)

  • Choi, Sung Yun;Kim, Young Min;Bae, Sun Hwan
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.7 no.1
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    • pp.102-107
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    • 2004
  • About 20% of intestinal tuberculosis have active pulmonary tuberculosis. Intestinal tuberculosis can develop by swallowing sputum which have active pulmonary tuberculosis and by ingestion of contagious milk. We report a case of intestinal tuberculosis complicated with pulmonary tuberculosis in a 15-year old aldelescent who could not cough out sputum because of known cerebral palsy. He was admitted because of 3 day history of fever and bloody stool. Chest PA showed both upper lobe consolidation. AFB stain and AFB PCR was positive for tuberculosis. Colon study showed abscence of haustral marking and lead pipe appearance due to stenosis of ascending colon and mucosal edema. Abdominal CT scan showed mild wall thickening in ascending colon. Despite the anti-tuberculosis therapy with first line drugs, fever accompanying pleural effusion developed. Second line drug with Isoniazid and Rifampin improved clinical manifestation. After the report on sensitivity, we readjusted the regimen, and clinical manifestations improved gradually.

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Pulmonary Resection Combined with Isoniazid-and Rifampin-based Drug Therapy for Patients with Multidrug-resistant Tuberculosis (다제내성 폐결핵 환자에서 폐절제술 후 일차 항결핵제 치료)

  • Park, Seung-Kyu;Kim, Jin-Hee;Kim, Jun-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.2
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    • pp.179-185
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    • 2005
  • Background : To evaluate the clinical efficacy of pulmonary resection combined with first-line antituberculous drug therapy in patients with well-localized, cavities-containing pulmonary multidrug-resistant tuberculosis (MDR-TB). Method : From February 1998, seventeen patients with well-localized, cavities-containing pulmonary MDR-TB were enrolled and followed prospectively up to December 2004. After radical pulmonary resection, the patients were treated with antituberculous drugs comprising of isoniazid (H), rifampin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) (3HERZS/3HERS/6HER). Results : All recovered isolates of M. tuberculosis were resistant to both isoniazid and rifampin, and to a mean of 4.8 antituberculous drugs (range, 2 to 7 drugs). Surgical procedures included lobectomy (13 patients), lobectomy plus segmentectomy (3 patients), and pneumonectomy (1 patient). The median time for postoperative sputum smear and culture conversion was 2 days (range, 1 to 23 days). Fifteen (94%) patients had durable cures (mean follow-up period, 39.0 months). One patient failed to convert her sputum and was successfully switched to second-line therapy; one patient developed active disease again almost 7 years later, likely due to re-infection with a new M. tuberculosis strain. Conclusion : Radical resection combined with administration of first-line antituberculous agents was effective in patients with well-localized, cavities-containing pulmonary MDR-TB.

Antiproliferative Activity of Marrubium persicum Extract in the MCF-7 Human Breast Cancer Cell Line

  • Hamedeyazdan, Sanaz;Fathiazad, Fatemeh;Sharifi, Simin;Nazemiyeh, Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5843-5848
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    • 2012
  • Aim: Developing antitumor drugs from natural products is receiving increasing interest worldwide due to limitations and side effects of therapy strategies for the second leading cause of disease related mortality, cancer. Methods: The antiproliferative activity of a methanolic extract from the aerial parts of Marrubium persicum extract was assessed with the MCF-7 breast cancer cell line using the MTT test for cell viability and cytotoxicity indices. In addition, antioxidant properties of the extract were evaluated by measuring its ability to scavenge free DPPH radicals. Moreover, the total phenolic and flavonoid content of the extract was determined based on Folin-Ciocalteu and colorimetric aluminum chloride methods. Results: The findings of the study for the antiproliferative activity of the methanolic extract of M. persicum showed that growth of MCF-7 cells was inhibited by the extract in a dose and time dependent manner, where a gradual increase of cytotoxicity effect has been achieved setting out on 200 ${\mu}g/mL$ concentration of the plant extract. The antioxidant assay revealed that the extract was a strong scavenger of DPPH radicals with an $RC_{50}$ value of 52 ${\mu}g/mL$. The total phenolic and flavonoids content of the plant extract was 409.3 mg gallic acid equivalent and 168.9 mg quercetin equivalent per 100g of dry plant material. Conclusion: Overall, M. persicum possesses potential antiproliferative and antioxidant activities on the malignant MCF-7 cell line that could be attributed to the high content of phenolics and flavonoids, and therefore warrants further exploration.