• Title/Summary/Keyword: chemotherapeutic agents

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Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics

  • Mathew, Ryan K.;Rutka, James T.
    • Journal of Korean Neurosurgical Society
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    • v.61 no.3
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    • pp.343-351
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    • 2018
  • Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study

  • Lee, Jee Youn;Son, Taeil;Cheong, Jae-Ho;Hyung, Woo Jin;Noh, Sung Hoon;Kim, Choong-Bai;Park, Chung-Gyu;Kim, Hyoung-Il
    • Journal of Gastric Cancer
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    • v.15 no.4
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    • pp.223-230
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    • 2015
  • Purpose: The purpose of this pilot study was to evaluate the association between adenosine triphosphate-based chemotherapy response assays (ATP-CRAs) and subsets of tumor infiltrating lymphocytes (TILs) in gastric cancer. Materials and Methods: In total, 15 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2011. Chemotherapy response assays were performed on tumor cells from these samples using 11 chemotherapeutic agents, including etoposide, doxorubicin, epirubicin, mitomycin, 5-fluorouracil (5-FU), oxaliplatin, irinotecan, docetaxel, paclitaxel, methotrexate, and cisplatin. TILs in the tissue samples were evaluated using antibodies specific for CD3, CD4, CD8, Foxp3, and Granzyme B. Results: The highest cancer cell death rates were induced by etoposide (44.8%), 5-FU (43.1%), and mitomycin (39.9%). Samples from 10 patients who were treated with 5-FU were divided into 5-FU-sensitive and -insensitive groups according to median cell death rate. No difference was observed in survival between the two groups (P=0.216). Only two patients were treated with a chemotherapeutic agent determined by an ATP-CRA and there was no significant difference in overall survival compared with that of patients treated with their physician's choice of chemotherapeutic agent (P=0.105). However, a high number of CD3 TILs was a favorable prognostic factor (P=0.008). Pearson's correlation analyses showed no association between cancer cell death rates in response to chemotherapeutic agents and subsets of TILs. Conclusions: Cancer cell death rates in response to specific chemotherapeutic agents were not significantly associated with the distribution of TIL subsets.

Plant Anticancer Agents and Cancer Chemopreventives: Recent Progress

  • Kinghorn, A.Douglas
    • Proceedings of the PSK Conference
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    • 2003.10a
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    • pp.58-59
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    • 2003
  • There is considerable interest in the screening of higher plant extracts in modem drug discovery programs to discover new chemotypes with potent and selective biological activity. Such work may be performed in different laboratory settings, including those in academic institutions. In the case of cancer, plants offer the potential for the discovery of both cancer chemotherapeutic agents and cancer chemopreventives. (omitted)

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BmKn-2 Scorpion Venom Peptide for Killing Oral Cancer Cells by Apoptosis

  • Tong-ngam, Pirut;Roytrakul, Sittiruk;Sritanaudomchai, Hathaitip
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2807-2811
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    • 2015
  • Scorpion venom peptides recently have attracted attention as alternative chemotherapeutic agents that may overcome the limitations of current drugs, providing specific cytotoxicity for cancer cells with an ability to bypass multidrug-resistance mechanisms, additive effects in combination therapy and safety. In the present study, BmKn-2 scorpion venom peptide and its derivatives were chosen for assessment of anticancer activities. BmKn-2 was identified as the most effective against human oral squamous cells carcinoma cell line (HSC-4) by screening assays with an $IC_{50}$ value of $29{\mu}g/ml$. The BmKn-2 peptide killed HSC-4 cells through induction of apoptosis, as confirmed by phase contrast microscopy and RT-PCR techniques. Typical morphological features of apoptosis including cell shrinkage and rounding characteristics were observed in treated HSC-4 cells. The results were further confirmed by increased expression of pro-apoptotic genes such as caspase-3, -7, and -9 but decrease mRNA level of anti-apoptotic BCL-2 in BmKn-2 treated cells, as determined by RT-PCR assay. In summary, the BmKn-2 scorpion venom peptide demonstrates specific membrane binding, growth inhibition and apoptogenic activity against human oral cancer cells.

Clinical Features of Oxaliplatin Induced Hypersensitivity Reactions and Therapeutic Approaches

  • Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1637-1641
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    • 2016
  • Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

A Clinical Study of Deep Neck Infection (경부심부감염의 임상적 고찰)

  • 이시형;김상윤;남순열;김준모;유승주
    • Korean Journal of Bronchoesophagology
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    • v.7 no.1
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    • pp.34-39
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    • 2001
  • Background and Objectives: Deep neck infections, which affect soft tissues and fascial compartments of the head and neck and their contents, have decreased after the develop ment of chemotherapeutic agents and antibiotics. However they may still result in significant morbidity and mortality despite the use of chemotherapeutic agents and antibiotics. Materials and Methods : A retrospective study was performed on 66 deep neck infections in patients admitted for diagnosis and treatment at Asan medical center from June 1994 to December 2000. Results : Age of the patients varied from 1 to 86-year-old and sex ratio of male to female was 1.2:1. Most frequently involved site was submandibular space (21.2%). Most common cause of infection was dental disease (28.8%). The isolated pathogenic organisms were Streptococcus species in 19 cases, Staphylococcus species in 7 cases, Klebsiella in 5 cases, mixed infection of Staphylococcus and Klebsiella in 3 cases and a case of Corynebacterium. 51 cases were treated surgically, 15 cases were medically. Mean duration of admission was 9.6 days in cases of single space infection, 17.5 days in multiple spaces, 8.1 days when the infection resulted in cellulitis, 13.4 days in abscess, 7.9 days when the infection treated medically and 13.4 days when treated surgically. Conclusion Early diagnosis and treatment is important to manage deep neck infection and the duration of admission was increased when the infection involved multiple spaces.

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Enzymes involved in folate metabolism and its implication for cancer treatment

  • Kim, Sung-Eun
    • Nutrition Research and Practice
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    • v.14 no.2
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    • pp.95-101
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    • 2020
  • BACKGROUND/OBJECTIVES: Folate plays a critical role in DNA synthesis and methylation. Intracellular folate homeostasis is maintained by the enzymes folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH). FPGS adds glutamate residues to folate upon its entry into the cell through a process known as polyglutamylation to enhance folate retention in the cell and to maintain a steady supply of utilizable folate derivatives for folate-dependent enzyme reactions. Thereafter, GGH catalyzes the hydrolysis of polyglutamylated folate into monoglutamylated folate, which can subsequently be exported from the cell. The objective of this review is to summarize the scientific evidence available on the effects of intracellular folate homeostasis-associated enzymes on cancer chemotherapy. METHODS: This review discusses the effects of FPGS and GGH on chemosensitivity to cancer chemotherapeutic agents such as antifolates, such as methotrexate, and 5-fluorouracil. RESULTS AND DISCUSSION: Polyglutamylated (anti)folates are better substrates for intracellular folate-dependent enzymes and retained for longer within cells. In addition to polyglutamylation of (anti)folates, FPGS and GGH modulate intracellular folate concentrations, which are an important determinant of chemosensitivity of cancer cells toward chemotherapeutic agents. Therefore, FPGS and GGH affect chemosensitivity to antifolates and 5-fluorouracil by altering intracellular retention status of antifolates and folate cofactors such as 5,10-methylenetetrahydrofolate, subsequently influencing the cytotoxic effects of 5-fluorouracil, respectively. Generally, high FPGS and/or low GGH activity is associated with increased chemosensitivity of cancer cells to methotrexate and 5-fluorouracil, while low FPGS and/or high GGH activity seems to correspond to resistance to these drugs. Further preclinical and clinical studies elucidating the pharmocogenetic ramifications of these enzyme-induced changes are warranted to provide a framework for developing rational, effective, safe, and customized chemotherapeutic practices.

Development of Anti-viral Agents from Natural Sources

  • Hattori, Masao
    • Plant Resources
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    • v.4 no.3
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    • pp.192-195
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    • 2001
  • Human immunodeficiency virus (HIV), the causative agent of AIDS, still continues to spread rapidly in the world population, especially in Africa and Southeast Asia. At present, two kinds of therapeutic approaches are used for treatment of AIDS. One is to target HIV reverse transcriptase, which is responsible for the viral genome transcription. The other is to inhibit HIV pretense PR, which is essential for the processing of viral proteins. Drug combinations based on these approaches can reduce the blood virus to an undetectable level. However, a small amount of virus may lurk inside the immune cells in a dormant state. Another major obstacle of long-term treatment of the disease is remarkable mutation in HIV. Most of the clinical chemotherapeutic agents have one or more of these problems. High cost and harmful side-effects further reduced the desirability of these drugs. In the course our studies on development of anti-HIV agents from natural products, we investigated various crude drugs for their inhibitory activity against HIV-induced cytopathic effects (CPE) in culture cells, HIV-pretense (PR), HIV-reverse transcriptase (RT) including ribonuclease H (RNase H), and HIV integrase (INT). In the present paper, some inhibitory substances relating to the development of anti-HIV agents are reported.

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Comparison of Survival in Stage IIB Osteosarcoma According to the Chemotherapeutic Protocols (Stage IIB 골육종환자에서 항암 화학요법의 종류에 따른 생존율 비교)

  • Jeon, Dae-Geun;Lee, Soo-Yong;Lee, Jong-Seok;Kim, Tae-Wan;Chung, Dong-Hwan
    • The Journal of the Korean bone and joint tumor society
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    • v.1 no.1
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    • pp.17-22
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    • 1995
  • From Sept. 1986 to Dec. 1992, seventy three cases of Enneking's stage IIB osteosarcoma of extremities, which were proved histologically, took neoadjuvant chemotherapy and completed our protocol. Their average age was 16.7 years(7 to 57). For neoadjuvant chemotherapy, 37 cases took high dose methotrexate(HDMTX)-adriamycin(ADR)-cisplatin(CDDP) regimen(HDMTX group) and 36 cases took ADR-CDDP(ADR-CDDP group). The average follow up was 17 months(2-63). According to Kaplan-Meier's plot, 5-year continuously disease free survival for whole 73 cases of neoadjuvant group was 45.2%, for HDMTX group 68.4%, for ADR-CDDP group 26.6%. There was significant stastical difference between these two groups(p<0.001), with log-rank test. There can be a different survival according to the chemotherapeutic protocols. Better results can be achieved through refined protocol and effective chemotherapeutic agents.

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Response Evaluation of Chemotherapy for Lung Cancer

  • Hwang, Ki-Eun;Kim, Hak-Ryul
    • Tuberculosis and Respiratory Diseases
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    • v.80 no.2
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    • pp.136-142
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    • 2017
  • Assessing response to therapy allows for prospective end point evaluation in clinical trials and serves as a guide to clinicians for making decisions. Recent prospective and randomized trials suggest the development of imaging techniques and introduction of new anti-cancer drugs. However, the revision of methods, or proposal of new methods to evaluate chemotherapeutic response, is not enough. This paper discusses the characteristics of the Response Evaluation Criteria In Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It also contains information about possible dilemmas arising from the application of response assessment by the latest version of the response evaluation method, or recently introduced chemotherapeutic agents. Further data reveals the problems and limitations caused by applying the existing RECIST criteria to anti-cancer immune therapy, and the application of a new technique, immune related response criteria, for the response assessment of immune therapy. Lastly, the paper includes a newly developing response evaluation method and suggests its developmental direction.