• Title/Summary/Keyword: Tumor therapy

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Transanal Tube Drainage as a Conservative Treatment for Anastomotic Leakage Following a Rectal Resection

  • Shalaby, Mostafa;Thabet, Waleed;Buonomo, Oreste;Di Lorenzo, Nicola;Morshed, Mosaad;Petrella, Giuseppe;Farid, Mohamed;Sileri, Pierpaolo
    • Annals of Coloproctology
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    • v.34 no.6
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    • pp.317-321
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    • 2018
  • Purpose: We evaluate the role of transanal tube drainage (TD) as a conservative treatment for patients with anastomotic leakage (AL). Methods: Patients treated for AL who had undergone a low or an ultralow anterior resection with colorectal or coloanal anastomosis for the treatment of rectal cancer between January 2013 and January 2017 were enrolled in this study. The data were collected prospectively and analyzed retrospectively. The primary outcomes were the diagnosis and the management of AL. Results: Two hundred thirteen consecutive patients, 122 males and 91 females, were included. The mean age was $66.91{\pm}11.15years$, and the median body mass index was $24kg/m^2$ (range, $20-35kg/m^2$). The median tumor distance from the anal verge was 8 cm (range, 4-12 cm). Ninety-three patients (44%) received neoadjuvant therapy for nodal disease and/or locally advanced rectal cancer. Only 13 patients (6%) developed AL. Six patients developed subclinical AL as they had a defunctioning ileostomy at the time of the initial procedure. They were treated conservatively with TD under endoscopic guidance in the endoscopy unit and received intravenous antibiotics. Six weeks after discharge, these 6 patients underwent follow-up flexible sigmoidoscopy which showed a completely healed anastomotic defect with no residual stenosis. Seven patients developed a clinically significant AL and required reoperation with pelvic abscess drainage and Hartmann colostomy formation. Conclusion: These results suggest that TD for management of patients with AL is safe, cheap, and effective. Salvaging the anastomosis will help decrease the need for Hartmann colostomy formation. Proper patient selection is important.

ATAD2 expression increases [18F]Fluorodeoxyglucose uptake value in lung adenocarcinoma via AKT-GLUT1/HK2 pathway

  • Sun, Tong;Du, Bulin;Diao, Yao;Li, Xuena;Chen, Song;Li, Yaming
    • BMB Reports
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    • v.52 no.7
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    • pp.457-462
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    • 2019
  • [18F]Fluorodeoxyglucose (FDG) PET/CT imaging has been widely used in the diagnosis of malignant tumors. ATPase family AAA domain-containing protein 2 (ATAD2) plays important roles in tumor growth, invasion and metastasis. However, the relationship between [18F]FDG accumulation and ATAD2 expression remains largely unknown. This study aimed to investigate the correlation between ATAD2 expression and [18F]FDG uptake in lung adenocarcinoma (LUAD), and elucidate its underlying molecular mechanisms. The results showed that ATAD2 expression was positively correlated with maximum standardized uptake value ($SUV_{max}$), total lesion glycolysis (TLG), glucose transporter type 1 (GLUT1) expression and hexokinase2 (HK2) expression in LUAD tissues. In addition, ATAD2 knockdown significantly inhibited the proliferation, tumorigenicity, migration, [18F]FDG uptake and lactate production of LUAD cells, while, ATAD2 overexpression exhibited the opposite effects. Furthermore, ATAD2 modulated the glycometabolism of LUAD via AKT-GLUT1/HK2 pathway, as assessed using LY294002 (an inhibitor of PI3K/AKT pathway). In summary, to explore the correlation between ATAD2 expression and glycometabolism is expected to bring good news for anti-energy metabolism therapy of cancers.

Review of Domestic Research on Korean Medicine for Pancreatic Cancer (췌장암에 대한 국내 한의학 연구 동향 고찰 - 국내 한의학 논문을 중심으로 -)

  • Han, Ga-jin;Jeong, Ha-yeong;Park, Eun-joo;Lee, A-reum;Lee, Jun-myung;Seong, Sin;Kim, Sung-su
    • The Journal of Internal Korean Medicine
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    • v.40 no.1
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    • pp.70-88
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    • 2019
  • Objective: This study investigated the trends in pancreatic cancer research on Korean medicine in order to establish a direction for further study. Methods: Pancreatic cancer research on Korean medicine was reviewed using databases such as OASIS, KoreanTK, KISS, RISS, KISTI, and NDSL. The search terms were "pancreatic cancer" "Korean medicine," and "herbal medicine." There was no restriction on publication dates, and the reviewed studies were analyzed according to the type of research. Results: Nineteen studies were reviewed. The numbers and types of research were as follows: 9 clinical studies including case reports, 2 review studies, and 8 in vitro studies; there was no in vivo study. Among the clinical research were 3 descriptive studies and 6 case reports. The baseline characteristics and quality of life of pancreatic cancer patients were analyzed in the descriptive studies. In the case reports, interventions such as herbal medicine, pharmacopuncture, and acupuncture were used. Research articles on the review of pancreatic cancer were titled "Preliminary Study for Development of Korean Medicine Clinical Practice Guideline for Pancreatic Cancer" and "Systemic Review on the Tumor Dormancy Therapy." Cell lines such as PANC-1, MIA PaCa-2, and AsPC-1 were used for in vitro studies. These studies have reported decreased cell viability, induced apoptosis, and changes in cancer-related gene expression. Conclusion: Through this review, we found that using Korean medicine for treating pancreatic cancer is applicable. However, due to overall limited the number of study, the benefit of Korean medicine for pancreatic cancer may be substantiated to a limited degree. Better methodological quality and large controlled trials are expected to further quantify the therapeutic effect of Korean medicine.

Structural characterization of the putative DNA-binding domain of CP2c and its relevance to zinc binding

  • Ryu, Ki-Sung;Jo, Ku-Sung;Kim, Na-Young;Jeon, Eun-Jae;Park, Sung Jean;Kim, Hyun-Hwi;Kim, Eun-Hee;Kim, Chan-Gil;Kim, Chul Geun;Won, Hyung-Sik
    • Journal of the Korean Magnetic Resonance Society
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    • v.23 no.1
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    • pp.20-25
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    • 2019
  • The transcription factor CP2c has been recently validated as an oncogenic protein that can serve as a promising target for anticancer therapy. We have recently documented that a recombinant protein corresponding to the putative DNA-binding region (residues 63-244) of CP2c adopted two different conformers, one of which is dominated by zinc binding. However, in the present study, a longer construct encompassing residues 63-302 appeared to form a single structural domain. This domain could be considered to adopt a functionally relevant fold, as the known specific binding of a dodecapeptide to this protein was evident. Hence, the residues 63-302 region rather than 63-244 can be regarded as a natively folded structural domain of CP2c. In addition, it was confirmed that zinc ions can bind to this putative DNA-binding domain of CP2c, which resulted in reduced stability of the protein. In this context, it is suggested that the mode of action of CP2c would resemble that of tumor suppressor p53.

Anti-inflammatory effect of aged black garlic on 12-O-tetradecanoylphorbol-13-acetate-induced dermatitis in mice

  • You, Bo Ram;Yoo, Jae-Myung;Baek, Seong Yeon;Kim, Mee Ree
    • Nutrition Research and Practice
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    • v.13 no.3
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    • pp.189-195
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    • 2019
  • BACKGROUND/OBJECTIVES: Although aged black garlic has various biological activities such as anti-allergy, anti-inflammation and neuroprotection, effect of aged black garlic on chemically contact dermatitis is unclarified. MATERIALS/METHODS: To evaluate anti-dermatitic activity of aged black garlic extract, we investigated effects of a fraction of aged black garlic extract (BG10) on both in vivo and in vitro. RESULTS: BG10 almost inhibited formation of nitric monoxide and interleukin-6 (IL-6; $IC_{50}$, $7.07{\mu}g/mL$) at $25{\mu}g/mL$, and dose-dependently reduced production of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$; $IC_{50}$, $52.07{\mu}g/mL$) and prostaglandin $E_2$ ($IC_{50}$, $38.46{\mu}g/mL$) in lipopolysaccharide-stimulated RAW264.7 cells. In addition, BG10 significantly inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear $NF-{\kappa}B$, and improved that of cytosolic levels of $NF-{\kappa}B$ and $I{\kappa}B{\alpha}$ in the cells. Consistent with in vitro studies, BG10 (0.5 mg/mL) not only reduced ear edema but also suppressed the formation of IL-6 and $TNF-{\alpha}$ induced by 12-O-tetradecanoylphorbol-13-acetate in ear tissues of mice. CONCLUSIONS: These findings suggest BG10 has anti-dermatitic activity through inhibiting activation of macrophages. Therefore, such effects of BG10 may provide information for the application of aged black garlic for prevention and therapy of contact dermatitis.

The Effects of Oral Cryotherapy on Oral Mucositis, Reactive Oxygen Series, Inflammatory Cytokines, and Oral Comfort in Gynecologic Cancer Patients Undergoing Chemotherapy: A Randomized Controlled Trial (구강 냉요법이 항암화학요법을 받는 부인암환자의 구내염, 활성산소, 염증성 사이토카인, 구강 안위감에 미치는 효과: 무작위대조군실험설계)

  • Shin, Nayeon;Kang, Younhee
    • Journal of Korean Academy of Nursing
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    • v.49 no.2
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    • pp.149-160
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    • 2019
  • Purpose: The purpose of this study was to examine the effects of oral cryotherapy on oral mucositis, reactive oxygen series, inflammatory cytokines, and oral comfort in patients undergoing chemotherapy for gynecologic cancers. Methods: Participants were randomly assigned to the experimental group (n=25, receiving oral cryotherapy during chemotherapy) and the control group (n=25, receiving the usual care consisting of 0.9% normal saline gargles three times before meals). Oral mucositis was assessed using the oral assessment guide, while oral comfort was assessed using the oral perception guide. Reactive oxygen series was measured as total oxidant stress, and the level of two inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-alpha ($TNF-{\alpha}$), were examined. The data were analyzed using t-test, chi-square test, Fisher's exact test, Mann-Whitney U-test, and repeated measures analysis of variance. Results: There was a significant difference in the oral mucositis score, reactive oxygen series score, $TNF-{\alpha}$ level, and oral comfort score between the two groups, and there were significant changes over time and in the group-by-time interactions. There was a significant difference in the IL-6 score between the two groups, but there were no significant changes over time or in the group-by-time interactions. Conclusion: The study results revealed that oral cryotherapy was more effective than the usual care regime of normal saline gargles for reducing oral mucositis, reactive oxygen series, and inflammatory cytokines and for improving oral comfort in gynecologic cancer patients undergoing chemotherapy.

Checkpoint-inhibition in ovarian cancer: rising star or just a dream?

  • Pietzner, Klaus;Nasser, Sara;Alavi, Sara;Darb-Esfahani, Silvia;Passler, Mona;Muallem, Mustafa Zelal;Sehouli, Jalid
    • Journal of Gynecologic Oncology
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    • v.29 no.6
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    • pp.93.1-93.11
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    • 2018
  • The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.

BRCA1/2 mutations, including large genomic rearrangements, among unselected ovarian cancer patients in Korea

  • Kim, Do-Hoon;Cho, Chi-Heum;Kwon, Sun Young;Ryoo, Nam-Hee;Jeon, Dong-Seok;Lee, Wonmok;Ha, Jung-Sook
    • Journal of Gynecologic Oncology
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    • v.29 no.6
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    • pp.90.1-90.12
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    • 2018
  • Objective: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. Methods: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. Results: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. Conclusion: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.

The Crucial Role of the Establishment of Computed Tomography Density Conversion Tables for Treating Brain or Head/Neck Tumors

  • Yang, Shu-Chin;Lo, Su-Hua;Shie, Li-Tsuen;Lee, Sung-Wei;Ho, Sheng-Yow
    • Progress in Medical Physics
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    • v.32 no.3
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    • pp.59-69
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    • 2021
  • Purpose: The relationship between computed tomography (CT) number and electron density (ED) has been investigated in previous studies. However, the role of these measures for guiding cancer treatment remains unclear. Methods: The CT number was plotted against ED for different imaging protocols. The CT number was imported into ED tables for the Pinnacle treatment planning system (TPS) and was used to determine the effect on dose calculations. Conversion tables for radiation dose calculations were generated and subsequently monitored using a dosimeter to determine the effect of different CT scanning protocols and treatment sites. These tables were used to retrospectively recalculate the radiation therapy plans for 41 patients after an incorrect scanning protocol was inadvertently used. The gamma index was further used to assess the dose distribution, percentage dose difference (DD), and distance-to-agreement (DTA). Results: For densities <1.1 g/cm3, the standard deviation of the CT number was ±0.6% and the greatest variation was noted for brain protocol conditions. For densities >1.1 g/cm3, the standard deviation of the CT number was ±21.2% and the greatest variation occurred for the tube voltage and head and neck (H&N) protocol conditions. These findings suggest that the factors most affecting the CT number are the tube voltage and treatment site (brain and H&N). Gamma index analyses for the 41 retrospective clinical cases, as well as brain metastases and H&N tumors, showed gamma passing rates >90% and <90% for the passing criterion of 2%/2 and 1%/1 mm, respectively. Conclusions: The CT protocol should be carefully decided for TPS. The correct protocol should be used for the corresponding TPS based on the treatment site because this especially affects the dose distribution for brain metastases and H&N tumor recognition. Such steps could help reduce systematic errors.

Valeriana jatamansi Jones Inhibits Rotavirus-Induced Diarrhea via Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway

  • Zhang, Bin;Wang, Yan;Jiang, Chunmao;Wu, Caihong;Guo, Guangfu;Chen, Xiaolan;Qiu, Shulei
    • Journal of Microbiology and Biotechnology
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    • v.31 no.8
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    • pp.1115-1122
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    • 2021
  • Rotavirus (RV), as the main cause of diarrhea in children under 5 years, contributes to various childhood diseases. Valeriana jatamansi Jones is a traditional Chinese herb and possesses antiviral effects. In this study we investigated the potential mechanisms of V. jatamansi Jones in RV-induced diarrhea. MTT assay was performed to evaluate cell proliferation and the diarrhea mice model was constructed using SA11 infection. Mice were administered V. jatamansi Jones and ribavirin. Diarrhea score was used to evaluate the treatment effect. The enzyme-linked immunosorbent assay was performed to detect the level of cytokines. Western blot and quantitative reverse transcription-PCR were used to determine protein and mRNA levels, respectively. Hematoxylin-eosin staining was applied to detect the pathological change of the small intestine. TdT-mediated dUTP nick-end labeling was conducted to determine the apoptosis rate. The results showed V. jatamansi Jones promoted MA104 proliferation. V. jatamansi Jones downregulated phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in protein level, which was consistent with the immunohistochemistry results. Moreover, V. jatamansi Jones combined with ribavirin regulated interleukin-1β (IL-1β), interferon γ, IL-6, tumor necrosis factor α, and IL-10, and suppressed secretory immunoglobulin A secretion to remove viruses and inhibit dehydration. V. jatamansi Jones + ribavirin facilitated the apoptosis of small intestine cells. In conclusion, V. jatamansi Jones may inhibit RV-induced diarrhea through PI3K/AKT signaling pathway, and could therefore be a potential therapy for diarrhea.