• Title/Summary/Keyword: therapeutic potential

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SLC35B2 Expression is Associated with a Poor Prognosis of Invasive Ductal Breast Carcinoma

  • Chim-ong, Anongruk;Thawornkuno, Charin;Chavalitshewinkoon-Petmitr, Porntip;Punyarit, Phaibul;Petmitr, Songsak
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6065-6070
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    • 2014
  • Background: Breast cancer is the most common malignancy in women worldwide, including Thailand, and is a major cause of mortality and morbidity, despite advances in diagnosis and treatment. Novel gene expression in breast cancer is a focus in searches for prognostic biomarkers and new therapeutic targets. Materials and Methods: The mRNA expression of novel B4GALT4, SLC35B2, and WDHD1 genes in breast cancer were examined in invasive ductal breast carcinoma (IDC) patients using quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR). Results: Among these genes, increased expression of SLC35B2 mRNA was significantly associated with TNM stage III + IV of IDC (p<0.001). Hence, up-regulation of SLC35B2 may serve as a prognostic biomarker for poor prognosis, and is also a potential therapeutic target in breast cancer.

Current Drugs and Drug Targets in Non-Small Cell Lung Cancer: Limitations and Opportunities

  • Daga, Aditi;Ansari, Afzal;Patel, Shanaya;Mirza, Sheefa;Rawal, Rakesh;Umrania, Valentina
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4147-4156
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    • 2015
  • Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

3-Deazaneplanocin A is a Promising Therapeutic Agent for Ovarian Cancer Cells

  • Shen, Liang;Cui, Jing;Pang, Ying-Xin;Ma, Yan-Hui;Liu, Pei-Shu
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2915-2918
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    • 2013
  • Background: Recent studies have shown that 3-deazaneplanocin A (DZNep), a well-known histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and induces apoptosis, while inhibiting proliferation and metastasis, in cancer cells, including acute myeloid leukemia, breast cancer and glioblastoma. However, little is known about effects of DZNep on ovarian cancer cells. Materials and Methods: We here therefore studied DZNep-treated A2780 ovarian cancer cells in vitro. Proliferation of ovarian cancer cells under treatment of DZNep was assessed by MTT and apoptosis by flow cytometry. Cell wound healing was applied to detect the migration. Finally, we used q-PCR to assess the migration-related gene, E-cadherin. Results: DZNep could inhibit the proliferation of A2780 and induce apoptosis Furthermore, it inhibited migration and increased the expression of E-cadherin (P<0.05). Conclusion: DZNep is a promising therapeutic agent for ovarian cancer cells, with potential to inhibite proliferation, induce apoptosis and decrease migration.

Tyrosine Kinase Inhibitors in Ph+ Chronic Myeloid Leukemia Therapy: a Review

  • Shah, Krupa;Parikh, Sonia;Rawal, Rakesh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3025-3033
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    • 2016
  • Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

Subsyndromal Bipolar Disorder (아증후군적 양극성 장애)

  • Kim, Moon-Doo;Jeon, Bong-Hee;Yoon, Bo-Hyun;Bhak, Won-Myong
    • Korean Journal of Biological Psychiatry
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    • v.18 no.4
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    • pp.217-224
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    • 2011
  • Subsyndromal bipolar symptoms are common during maintenance treatment and appear to be associated with relapse into an episode of the same polarity. This implies subsyndromal symptoms are an important problem in recurrent bipolar disorder and require more additive and infallible therapeutic intervention. Undetected, untreated subsyndromal states lead patients to have poor prognosis and quality of life. The combination of a long undetected illness and significant psychosocial impairment renders early identification and intervention vital for the treatment of bipolar disorders. Methods for early identification includes finding prodromes, using screening tools such as the HCL-32 (Hypomania Checklist-32) and the BSDS (bipolar spectrum diagnostic scale). Various augmentation treatment methods would be needed to reduce subsyndromal symptoms, especially, psychosocial treatment has the potential to help patients address the multiple psychosocial problems associated with this chronic illness. To overcome difficulties of diagnosing subsyndromal disorder and to treat it appropriately, a staging system was suggested by some researchers. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in treatment planning and prognosis of bipolar disorder, and emphasize the importance of early intervention. Further research is required in this exciting and novel area.

Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation

  • Kweon, Hae-Jin;Suh, Byung-Chang
    • BMB Reports
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    • v.46 no.6
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    • pp.295-304
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    • 2013
  • Extracellular acidification occurs not only in pathological conditions such as inflammation and brain ischemia, but also in normal physiological conditions such as synaptic transmission. Acid-sensing ion channels (ASICs) can detect a broad range of physiological pH changes during pathological and synaptic cellular activities. ASICs are voltage-independent, proton-gated cation channels widely expressed throughout the central and peripheral nervous system. Activation of ASICs is involved in pain perception, synaptic plasticity, learning and memory, fear, ischemic neuronal injury, seizure termination, neuronal degeneration, and mechanosensation. Therefore, ASICs emerge as potential therapeutic targets for manipulating pain and neurological diseases. The activity of these channels can be regulated by many factors such as lactate, $Zn^{2+}$, and Phe-Met-Arg-Phe amide (FMRFamide)-like neuropeptides by interacting with the channel's large extracellular loop. ASICs are also modulated by G protein-coupled receptors such as CB1 cannabinoid receptors and 5-$HT_2$. This review focuses on the physiological roles of ASICs and the molecular mechanisms by which these channels are regulated.

Constant State of Sigmoid Colon Cancer with Liver Metastasis by Herbal Medicine : A Case with an 8-year Follow-up (간 전이를 동반한 결장암 환자에서 한방치료의 효과 : 8년간의 추적조사를 통한 증례보고)

  • Kim, Jung-Sun;Yoo, Hwa-Seung;Cho, Chong-Kwan;Lee, Yeon-Weol
    • The Journal of Internal Korean Medicine
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    • v.28 no.3
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    • pp.662-669
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    • 2007
  • Objectives : The aim of the present study is to derive further studies evaluating the effectiveness of oriental medical treatment on colon cancer patients. We present a case of a patient diagnosed with colon cancer with colon cancer with liver metastasis who has survived more than 8 years. Methods : We followed all of treatments and examination. We prescribed the patient to take HangAm-dan(HAD) three times a day for 5 years and 1 month from January, 2000 to February, 2005. Abdominal computed tomography(CT) was performed to evaluate the therapeutic efficacy and measuring concentration of carcinoembryonic antigen(CEA) in blood serum was also performed to monitor therapeutic response. Results : The patient was diagnosed with liver metastasis in September of 1999 but has survived for over 8 years since. Abdomen CT show no interval change. Conclusions : This case may give us a possibility that oriental medical treatment offers potential benefits for patients with colon cancer.

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Systematic Studies on Galgeun-tang(gegen-tang, kakkon-to) for Establishment of Evidence Based Medicine (표준한방처방의 EBM 구축을 위한 갈근탕(葛根湯) 문헌 분석 연구)

  • Lee, Jun-Kyoung;Kim, Jung-Hoon;Shin, Hyeun-Kyoo
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.103-111
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    • 2011
  • Objectives : The purpose of this report was to provide the information of activity and safety of galgeun-tang by analyzing domestic/international papers and theses about galgeun-tang. Methods : Domestic/international papers and theses related to galgeun-tang were reviewed and analyzed. These papers were then classified by efficacy, or clinical trials. Results : The basic pharmacological experiment showed antipyretic, analgesic and anti-virus and anti-oxidant efficacy of galgeun-tang. In the case report of galgeun-tang, it showed therapeutic effect for patient with chronic rhinitis. But administration of galgeun-tang induced pruritic eruption in the two case report as a side effects of galgeun-tang. Conclutions : galgeun-tang showed tantipyretic, analgesic and anti-virus and anti-oxidant efficacy in the basic pharmacological experiment. Also, galgeun-tang showed therapeutic effect for patient with chronic rhinitis. But it was reported that galgeun-tang induced pruritic eruption in two case report, so physicians should be aware of the potential side effects.

Direct Intramuscular Gene Transfer of Naked DNA Expressing Human Vascular Endothelial Growth Factor (pCK-VEGF) Enhances Collateral Growth in a Rabbit Ischemic Hind Limb Model (토끼 허혈성 하지 모델에서 VEGF 발현 Naked DNA 벡터인 pCK-VEGF의 근육내 투여가 측부혈관형성에 미치는 영향)

  • 채제건;전현순;박은진;김종묵;김덕경;김선영
    • YAKHAK HOEJI
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    • v.45 no.1
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    • pp.108-115
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    • 2001
  • We have recently reported the development of a high efficiency expression vector, pCK, which can drive a high level of gene expression in mouse skeletal muscle. In this study, we tested the therapeutic potential of pCK expressing human VEGF165, pCK-VEGF in the rabbit ischemic hind limb model. To determine the optimal dose of plasmid DNA, various concentrations of pCK-CAT were injected into the muscle of a rabbit hind limb and the levels of CAT activity were determined. It was found that the expression level of the exogenously added gene became stable between 250 and 1,000 $\mu$g. Based on this result, we tested whether intramuscular transfer of 500$\mu$g of pCK-VEGF could actually modulate collateral vessel development in a rabbit ischemic hind limb model. It was found that relative to the control group injected with the pCK lacking the VEGF sequence, single intramuscular doses (500$\mu$g) of pCK-VEGF produced statistically significant augmentation of collateral vessels as determined by the angiographic vessel count, maximal blood flow by Doppler flowmeter and the number of capillaries by histology. These results suggest that a single 500$\mu$g-delivery of pCK-VEGF is potent enough to induce sufficient angiogenic activity and achieve therapeutic benefit on this rabbit model.

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The Efficacy of Shikonin on Cartilage Protection in a Mouse Model of Rheumatoid Arthritis

  • Kim, Young-Ock;Hong, Seung-Jae;Yim, Sung-Vin
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.4
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    • pp.199-204
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    • 2010
  • The potential therapeutic action of shikonin in an experimental model of rheumatoid arthritis (RA) was investigated. As a RA animal model, DBA/1J mice were immunized two times with type II collagen. After the second collagen immunization, mice were orally administered shikonin (2 mg/kg) once a day for 35 days, and the incidence, clinical score, bone mineral density (BMD), bone mineral content (BMC) and joint histopathology were evaluated. BMD in the proximal regions of the tibia largely increased in the shikonin treatment group compared with the control group. We also examined the effect of shikonin on inflammatory cytokines and cartilage protection. Shikonin treatment significantly reduced the incidence and severity of collagen-induced arthritis (CIA), markedly abrogating joint swelling and cartilage destruction. Shikonin also significantly inhibited the production of matrix metalloproteinase (MMP)-1 and up-regulated tissue inhibitors of metalloproteinase (TIMP)-1 in mice with CIA. In conclusion, shikonin exerted therapeutic effects through regulation of MMP/TIMP; these results suggest that shikonin is an outstanding candidate as a cartilage protective medicine for RA.