• Title/Summary/Keyword: Cytotoxic therapy

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Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

Radiotherapy and immune checkpoint blockades: a snapshot in 2016

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • v.34 no.4
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    • pp.250-259
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    • 2016
  • Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect. This review will cover the current issue and the future perspectives for combined with radiotherapy and immune checkpoint blockades based upon the available preclinical and clinical data.

Induction of Apoptosis with Moringa oleifera Fruits in HCT116 Human Colon Cancer Cells Via Intrinsic Pathway

  • Guon, Tae-Eun;Chung, Ha Sook
    • Natural Product Sciences
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    • v.23 no.4
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    • pp.227-234
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    • 2017
  • Moringa oleifera Lam (M. oleifera, Moringaceae) is a tree of the Moringaceae family that can reach a height of between 5 and 10 m. The current paper presents cytotoxic effect of M. oleifera fruits and its flavonoids 1 and 2. The viability of HCT116 human colon cancer cells were 38.5% reduced by $150{\mu}g/mL$ of ethanolic extracts in a concentration-dependent manner; in addition, we observed the apoptotic features of cell shrinkage and decreased cell size. Bcl-2 family proteins were regulated as determined by Western blotting analysis, suggesting that M. oleifera fruits and their flavonoids 1 and 2 induced apoptosis through an intrinsic pathway. Based on our findings, 70% ethanolic extracts of M. oleifera fruits and flavonoids 1 and 2 might be useful as cytotoxic agents in colorectal cancer therapy.

Effect of thymus extract on the activation of cytotoxic and accessory functions of tumor-associated macrophages

  • Shrivastava, Pratima;Singh, Sukh Mahendra;Singh, Nisha
    • Advances in Traditional Medicine
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    • v.4 no.1
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    • pp.9-17
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    • 2004
  • The present investigation was under taken to study whether the tumor-associated macrophages (TAM) of Daltons lymphoma (DL), a spontaneous transplantable murine T cell lymphoma can be activated to tumoricidal state by crude thymus extract. Intraperitoneal administration of thymus extract to DL-bearing mice resulted in activation of TAM with an enhanced IL-1, TNF and antigen presenting ability. It was found that treatment with thymus extract could also enhance the phagocytic and cytotoxic activity of TAM. However, only a marginal increase in arginase activity was observed. Till date to the best of our knowledge the effect of crude thymus extract on the activation of tumor associated macrophages has not been investigated, this study provides a new piece of information in the area of thymus therapy.

Radiation Dosimetry for Radionuclide Therapy (동위원소 치료 관련 방사선 흡수선량평가)

  • Kim, Eun-Hee
    • 대한핵의학회:학술대회논문집
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    • 2001.05a
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    • pp.4-10
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    • 2001
  • The radionuclide therapy is a protocol for tumor control by administering radionuclides as the cytotoxic agents. Radionuclides concentrated at the site of cancerous lesion are expected to kill the cancerous cells with minimal injury to the normal tissue. The efficacy of every radionuclide treatment can be evaluated by examining the toxicity to the lesion differentiated from that to the normal tissue. Radiation dosimetry is the procedure of quantitating the energy absorbed by target volumes of interest. Dosimetric information plays an indicator of the expected radiation damage and thus the therapeutic efficacy. This paper summarizes the dosimetric aspects in radionuclide therapy in terms of radionuclides of use, radiation dosimetry methodology and considerations for each treatment in practical use.

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Contradictory Relationships between Cancer and Normal Cells and Implications for Anti-cancer Therapy

  • Gou, Xing-Chun;Kong, Derek;Tang, Xu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.13
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    • pp.5143-5147
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    • 2015
  • Cancer treatment remains a serious problem worldwide. Analysis of the relationship between cancer cells and normal cells reveals that these two share characteristics in contradiction, thus could be analyzed by using contradictory principles. Under the theory of contradictory principles, induction of a dormant state or reversal of cancer cells is an important treatment strategy beyond traditional cytotoxic therapy. Normal cells are also the targets and under the influence of anti-cancer treatments and should be considered during therapy. Findings based on crosstalk between these two cell types may offer opportunities for the development of new biomarkers and therapies.

Boronated Porphyrins and Chlorins as Potential Anticancer Drugs

  • Ol'shevskaya, Valentina A.;Zaytsev, Andrey V.;Savchenko, Arina N.;Shtil, Alexander A.;Cheong, Chan-Seong;Kalinin, Valery N.
    • Bulletin of the Korean Chemical Society
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    • v.28 no.11
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    • pp.1910-1916
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    • 2007
  • Analyzed are recent advances in design of novel boronared conjugates of synthetic and natural porphyrins and chlorins. These compounds showed high efficacy as cytotoxic agents for tumor cells in culture and as phototoxins in photodynamic therapy of tumor xenografts. Thus, boronated porphyrins and chlorins emerge as promising class of anticancer agents with potentially multiple advantages: the chemotherapeutic drugs alone and photo- and radiosensitizers in binary treatments.

A Case of Therapy-related Myelodysplastic Syndrome after FOLFOX4 Chemotherapy in Advanced Gastric Cancer

  • Kwang Il Seo;Sung Eun Kim;Moo In Park;Seun Ja Park;Won Moon;You Jin Han
    • Journal of Digestive Cancer Research
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    • v.4 no.1
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    • pp.43-45
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    • 2016
  • Oxaliplatin is a third-generation platinum compound widely used to treat gastrointestinal malignancy. One of the major side effects of oxaliplatin is thrombocytopenia, the development of which can limit appropriate treatment. We report a 38-year-old man with advanced gastric cancer who developed severe thrombocytopenia after FOLFOX4 (oxaliplatin, leucovorin, and fluorouracil) chemotherapy. The thrombocytopenia was associated with therapy-related myelodysplastic syndrome after cytotoxic chemotherapy and was confirmed by bone marrow biopsy and genetic study. Therefore, physicians should be aware of therapy-related hematologic complications, especially with an oxaliplatin-based chemoregimen, and might consider the bone marrow study in those patients.

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The various mechanisms of Korean traditional medicines for anti-cancer (한약의 다양한 항암기전)

  • Park, Yeong-Chul;Park, Yong-Ki;Lee, Sun-Dong
    • The Korea Journal of Herbology
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    • v.27 no.3
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    • pp.39-55
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    • 2012
  • Objectives : Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of herbal medicine. This paper was aimed to review herbal medicine playing its anticancer role in terms of apoptosis, inflammation control, differentiation and telomerase. Methods : New studies for tang, medicinal herb itself or effective ingradients of medicinal herb showing anti-cancer effectiveness were reviewed and summarized in terms of pharmacological action. Results : Ethanol extracts of $Spatholobus$ $suberectus$ greatly inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. $Scutellaria$ $baicalensis$ may be responsible for its anticancer activity showing inhibition of $PGE_2$ synthesis via suppression of COX-2 expression. Saikosaponins isolated from $Bupleurum$ induced the differentiation of C6 glioma cells, cancer cells, into astrocytes, normal cells. Acetone extract of $Bupleurum$ $scorzonerifolium$ inhibited proliferation of human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Conclusions : Herbal medicine inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. Inflammation persisting for a decade eventually elevates the risk of cancer sufficiently that it is discernible in case control epidemiological studies. Differentiation therapy is defined as a therapy to treat cancers by inducing differentiation of the stem cells. Telomerase expression is a hallmark of cancer. Nearly the complete spectrum of human tumors has been shown to be telomerase positive.

Synthesis and Evaluation of a Ligand Targeting the Somatostatin Receptor for Drug Delivery to Tumor Cell (암세포 내로의 약물 전달 증진 목적의 신규 소마토스타틴 수용체 타겟리간드 합성 및 평가)

  • Choi, SunJu;Hong, YoungDon;Lee, SoYoung;Jung, SungHee
    • Journal of Radiation Industry
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    • v.9 no.4
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    • pp.193-198
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    • 2015
  • Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, $^{177}Lu$-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological half-life of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.