• Title/Summary/Keyword: Novel cancer therapy

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131I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

  • Ma, Jun;Wang, Jian-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7441-7447
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    • 2015
  • Objective: This study evaluated the safety and objective response of combining $^{131}I$-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were $3.19{\pm}1.01Gy$ and $0.55{\pm}0.22Gy$, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved ($6.82{\pm}1.28$ vs. $4.7{\pm}1.14months$, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

Prevelance of Common YMDD Motif Mutations in Long Term Treated Chronic HBV Infections in a Turkish Population

  • Alagozlu, Hakan;Ozdemir, Ozturk;Koksal, Binnur;Yilmaz, Abdulkerim;Coskun, Mahmut
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5489-5494
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    • 2013
  • In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

A Novel Implantable Cerebrospinal Fluid Reservoir : A Pilot Study

  • Byun, Yoon Hwan;Gwak, Ho Shin;Kwon, Ji-Woong;Kim, Kwang Gi;Shin, Sang Hoon;Lee, Seung Hoon;Yoo, Heon
    • Journal of Korean Neurosurgical Society
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    • v.61 no.5
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    • pp.640-644
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    • 2018
  • Objective : The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port. Methods : The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation. Results : The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port. Conclusion : V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.

Autophagy: a lysosomal degradation process for cellular homeostasis and its relationship with oral squamous cell carcinoma

  • Jung, Junyoung;Kim, Joungmok;Kim, Jeong Hee
    • International Journal of Oral Biology
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    • v.46 no.2
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    • pp.74-80
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    • 2021
  • Autophagy is an evolutionarily well-conserved cellular homeostasis program that responds to various cellular stresses and degrades unnecessary or harmful intracellular materials in lysosomes. Accumulating evidence has shown that autophagy dysfunction often results in various human pathophysiological conditions, including metabolic disorders, cancers, and neurodegenerative diseases. The discovery of an autophagy machinery protein network has revealed underlying molecular mechanisms of autophagy, and advances in the understanding of its regulatory mechanism have provided novel therapeutic targets for treating human diseases. Recently, reports have emerged on the involvement of autophagy in oral squamous cell carcinoma (OSCC). Although the role of autophagy in cancer therapy is controversial, the beneficial use of the induction of autophagic cell death in OSCC has drawn significant attention. In this review, the types of autophagy, mechanism of autophagosome biogenesis, and modulating molecules and therapeutic candidates affecting the induction of autophagic cell death in OSCC are briefly described.

Siamese Crocodile White Blood Cell Extract Inhibits Cell Proliferation and Promotes Autophagy in Multiple Cancer Cell Lines

  • Phosri, Santi;Jangpromma, Nisachon;Chang, Leng Chee;Tan, Ghee T.;Wongwiwatthananukit, Supakit;Maijaroen, Surachai;Anwised, Preeyanan;Payoungkiattikun, Wisarut;Klaynongsruang, Sompong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.1007-1021
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    • 2018
  • Cancer represents one of the most significant threats to human health on a global scale. Hence, the development of effective cancer prevention strategies, as well as the discovery of novel therapeutic agents against cancer, is urgently required. In light of this challenge, this research aimed to evaluate the effects of several potent bioactive peptides and proteins contained in crocodile white blood cell extract (cWBC) against LU-1, LNCaP, PC-3, MCF-7, and CaCo-2 cancer cell lines. The results demonstrate that 25, 50, 100, and $200{\mu}g/ml$ cWBC exhibits a strong cytotoxic effect against all investigated cell lines ($IC_{50}$ $70.34-101.0{\mu}g/ml$), while showing no signs of cytotoxicity towards noncancerous Vero and HaCaT cells. Specifically, cWBC treatment caused a significant reduction in the cancerous cells' colony forming ability. A remarkable suppression of cancerous cell migration was observed after treatment with cWBC, indicating potent antimetastatic properties. The mechanism involved in the cancer cell cytotoxicity of cWBC may be related to apoptosis induction, as evidenced by typical apoptotic morphology features. Moreover, certain cWBC concentrations induced significant overproduction of ROS and significantly inhibited the $S-G_2/M$ transition in the cancer cell. The molecular mechanisms of cWBC in apoptosis induction were to decrease Bcl-2 and XIAP expression levels and increase the expression levels of caspase-3, caspase-8, and p53. These led to a decrease in the expression level of the cell cycle-associated gene cyclin-B1 and the arrest of cell population growth. Consequently, these findings demonstrate the prospect of the use of cWBC for cancer therapy.

Review of Anti-Leukemia Effects from Medicinal Plants (항 백혈병작용에 관련된 천연물의 자료조사)

  • Pae Hyun Ock;Lim Chang Kyung;Jang Seon Il;Han Dong Min;An Won Gun;Yoon Yoo Sik;Chon Byung Hun;Kim Won Sin;Yun Young Gab
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.3
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    • pp.605-610
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    • 2003
  • According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.

Locally Advanced, Unresectable Pancreatic Cancer Treated by Stereotactic Radiation Therapy (국소적으로 진행된, 절제 불가능한 췌장암에서 정위 방사선 치료)

  • Choi Chul-Won;Kim Mi-Sook;Cho Chul-Koo;Yoo Seong-Yul;Yang Kwang-Mo;Yoo Hyung-Jun;Lee Dong-Han;Ji Young-Hoon;Han Chul-Ju;Kim Jin;Kim Young-Han
    • Radiation Oncology Journal
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    • v.24 no.1
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    • pp.11-20
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    • 2006
  • Puroose: In order to find out whether stereotactic radiation therapy (RT) using CyberKnife (CK) could improve survival rate and lower acute toxicity compared to conventional RT. Materials and Methods: From April 2003 through April 2004, 19 patients with Eastern Cooperative Oncology Group (ECOG) performance status ${\leq}3$ and locally advanced pancreas cancer without distant metastasis, evaluated by CT or PET/CT, were included. We administered stereotactic RT consisting of either 33 Gy, 36 Gy or 39 Gy in 3 fractions to 6, 4 and 9 patients, respectively, in an effort to increase the radiation dose step by step, and analyzed the survival rate and gastrointestinal toxicities by the acute radiation morbidity criteria of Radiation Therapeutic Oncology Group (RTOG). Prognostic factors of age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9, planning target volume (PTV), and adjacent organ and vessel invasion on CT scan were evaluated by Log Rank test. Results: The median survival time was 11 months with 1-year survival rate of 36.8%. During follow-up period (range $3{\sim}20$ months, median 10 months), no significant gastrointestinal acute toxicity (RTOG grade 3) was observed. In univariate analysis, age, sex, ECOG performance score, chemotherapy, bypass surgery, radiation dose, CA 19-9 level, and adjacent organ and vessel invasion did not show any significant changes of survival rate, however, patients with PTV (80 cc showed more favorable survival rate than those with PTV>80 cc (p-value<0.05). In multivariate analysis, age younger than 65 years and PTV>80 cc showed better survival rate. Conclusion: In terms of survival, the efficacy of stereotactic radiation therapy using CK was found to be superior or similar to other recent studies achieved with conventional RT with intensive chemotherapy, high dose conformal RT, intraoperative RT (IORT), or intensity modulated RT (IMRT). Furthermore, severe toxicity was not observed. Short treatment time in relation to the short life expectancy gave patients more convenience and, finally, quality of life would be increased. Consequently, this could be regarded as an effective novel treatment modality for locally advanced, unresectable pancreas cancer. PTV would be a helpful prognostic factor for CK.

Trend Analysis of Affective Computing Technology for Diagnosis and Therapy of Autistic Spectrum Disorder (자폐스펙트럼장애 진단 및 치료를 위한 감성 컴퓨팅 기술 동향 분석)

  • Yoon, Hyun-Joong;Chung, Seong-Youb
    • Science of Emotion and Sensibility
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    • v.13 no.3
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    • pp.429-440
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    • 2010
  • It is known that as many as 1 in 91 children are diagnosed with an autistic spectrum disorder, and the incidence rate of the autistic spectrum disorder is much higher than that of cancer in Korea. It is necessary to develop a novel technology to sense their emotional status and give proper psychological diagnosis and therapy, since the children with autistic spectrum disorder usually do not express their own emotional status. This article presents the state-of-the-arts on the affective computing technologies that include recognition of emotional status through bio-sensing and virtual affective agent modeling, and then proposes a novel system architecture for diagnosis and therapy of autistic spectrum disorder. The diagnosis and therapy system of autistic spectrum disorder is composed of bio-sensing module, virtual environment module with affective agents, and haptic interface module. The architecture proposed in this paper will enhance the objectivity to diagnose autism spectrum disorders, and enable continuous treatment in daily life.

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