• Title/Summary/Keyword: chemotherapeutic agents

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Mechanism and Treatment of Chemotherapy-induced Peripheral Neuropathy (항암치료와 연관된 신경병증의 발생 기전 및 치료)

  • Dong Kee Jang
    • Journal of Digestive Cancer Research
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    • v.11 no.1
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    • pp.45-48
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    • 2023
  • One of the most common side effects of chemotherapeutic agents is chemotherapy-induced peripheral neuropathy (CIPN). The occurrence of CIPN is increasing as the survival rate of patients with cancer improves and the cumulative dose or duration of neurotoxic drugs increases. Approximately 30-40% of patients receiving neurologically toxic drugs experience CIPN, which eventually increases the burden of medical expenses. However, preventive measures against CIPN have not yet been established. Clinical trials have tested various drugs for the management of neuropathic pain, but only duloxetine has shown any significant effect. Further studies should evaluate nonpharmaceutical treatments, such as exercise.

Recent Findings on the Mechanism of Cisplatin-Induced Renal Cytotoxicity and Therapeutic Potential of Natural Compounds

  • Lee, Dahae;Choi, Sungyoul;Yamabe, Noriko;Kim, Ki Hyun;Kang, Ki Sung
    • Natural Product Sciences
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    • v.26 no.1
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    • pp.28-49
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    • 2020
  • The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

A Case of Bleomycin Induced Bronchiolitis Obliterans Organizing Pneumonia (Bleomycin에 의해 유발된 Bronchiolitis Obliterans Organizing Pneumonia 1예)

  • Oh, Hye-Lim;Kang, Hong-Mo;Choi, Cheon-Woong;Lee, Ho-Jong;Cho, Yong-Seun;Yoo, Jee-Hong
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.504-509
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    • 2001
  • There are numerous agents with potential toxic effects on the lung. In particular, cytotoxic drugs constitute the largest and most important group of agents associated with lung toxicity. Bleomycin is commonly used, either alone or in combination with other chemotherapeutic agents, in the treatment of squamous cell carcinoma(head and neck, esophagus, and genitourinary tract), lymphoma, and germ cell tumor. One of the therapeutic advantages of bleomycin is its minimal bone marrow toxicity. However, pulmonary toxicity is one of the most serious adverse side effects. Classically, pulmonary toxicity manifests as a diffuse interstitial process or less commonly as a hypersensitivity reaction. This pulmonary toxicity is generally considered to be dose related and can progress to a fatal fibrosis. It is also possible that bronchiolitis obliterans organizing pneumonia(BOOP) is another manifestation of bleomycin induced toxicity. Bleomycin induced BOOP is less common and has a favorable response to steroid therapy. Here we present a case that demonstrates a BOOP, secondary to a relatively small cumulative dose of bleomycin($225mg/m^2$), may be reversible.

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Anti-cancer Effects of Bujeonghangamtang on Human Pancreatic Cancer Cell Line PANC-1 (부정항암탕(扶正抗癌湯)의 사람 췌장암 세포주 PANC-1에 대한 항종양(抗腫瘍) 효과(效果))

  • Kim, Hoon;Won, Jin-Hee;Moon, Goo
    • Herbal Formula Science
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    • v.15 no.1
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    • pp.213-228
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    • 2007
  • Objectives : The purpose of this report was to investigate the chemotherapeutic effect of Bujeonghangamtang against cancer cells. Materials and Methods : Various cancer cell lines including PANC-1, C6 glioma, SH-SY5Y, HepG2, and MCF-7 cells, were used. Apoptosis was determined by DAPI nuclei staining and flow cytometry in PANC-1 cells treated with 1 mg/ml Bujeonghangamtang for 48 hr. Expression of cell cycle arrest mediators including, cdc2p34 and cyclin B1 proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Result : Bujeonghangamtang induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. but not C6 glioma, SH-SY5Y, HepG2, and MCF-7 cells. PANC-1 cells were markedly sensitive to Bujeonghangamtang. Treatment with Bujeonghangamtang resulted in the decreased expression of cdc2p34 and cyclin B1. Treatment with Bujeonghangamtang also increased the ROS production and induced mitochondrial dysfunction. Conclusion : Bujeonghangamtang exerted cytotoxicity against human Pancreatic cancer cells via cell cycle arrest-mediated apoptotic signaling including ROS production and mitochondrial dysfunction. Our data suggest that Bujeonghangamtang may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

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MICRODONTIA IN A CHILD TREATED WITH CHEMOTHERAPEUTIC AGENT (항암 화학치료를 받은 아동의 치아발육이상 : 증례 보고)

  • Kye, Hi-Ran;Lee, Jae-Ho;Kim, Seong-Oh;Sohn, Heung-Kyu
    • Journal of the korean academy of Pediatric Dentistry
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    • v.26 no.1
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    • pp.146-150
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    • 1999
  • With the improved cure rates for childhood malignant conditions in the past decade, late effects of cancer therapy must be recognized to minimize their impact on the quality of life in long-term survivors. Chemoradiation therapy is a major part of pediatric oncology treatment and is implicated in causing tooth agenesis, microdontia, root shortening, early apical closure, and coronal hypocalcification. Dental development may be affected by illness, trauma, chemotherapy, or radiation therapy at any point prior to complete maturation. Treatment given during the first 3.5 years of life was more likely to affect the dental lamina and crown formation and result in a small tooth. Dental treatment affected by chemoradiation damage to developing teeth includes orthodontic tooth movement, prosthetic abutment consideration, periodontal health, space maintenance, requirement for home fluoride regimens to protect hypomineralized teeth, and enodontic procedures. Dental abnormalities are common in patients treated for cancer, and these children require aggressive dental follow-up. Meticulous surveillance may facilitate detection of abnormalities, enabling the dental practitioner to intervene earlier in promoting a more aggressive regimen of oral care, thus reducing the morbidity associated with dental sequelae of oncotherapy, specifically periodontal disease and malocclusion. In this case, we report microdontia of all permanent second premolar and second molar in an 8 year old boy treated with chemotherapeutic agents during period of active dental development(14 months to 38 months of age).

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The comparative study of treatment method on adriamycin-induced extravasation injury (Adriamycin의 혈관외 유출 손상 후 치료 방법의 비교)

  • Moon, In-Sun;Lee, Chang-Ho;Kwon, Yong-Seok;Lee, Keun-Cheol;Kim, Seok-Kwun
    • Archives of Plastic Surgery
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    • v.36 no.3
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    • pp.269-276
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    • 2009
  • Purpose: Local skin necrosis after extravasation of adriamycin, a widely used chemotherapeutic agent, is a common problem in cancer patients. The extravasation of chemotherapeutic agents yields severe inflammatory responses, crust formation, skin necrosis, and ulceration. Even though several treatment options have been proposed for extravasation injury, there is still controversy regarding the management of such lesions. Thus the aim of this study was to compare the efficacy of saline injection(Group 1), hydrocortisone injection(Group 2), propranolol injection(Group 3) and early surgical excision as a treatment(Group 4) in a rat extravasation model. Methods: The authors planned forty mature male Sprague - Dawley rats were divided into 4 groups and each group contained 10 rats. Administration of adriamycin($1.0mg/m{\ell}$) $1.5m{\ell}$ by subcutaneous injection on the dorsal side of the rats was followed by protocol. The treatment options were applied 2 hours after adriamycin injection. At the end of the 5th days, the presence and size of ulcers at the injection site were measured. 3 weeks after injection, a histopathologic examination was performed for each treatment and control group. T - tests were used to analyze the differences between the measurements. Results: Propranolol significantly improved tissue recovery compared with control group and other groups. These data suggest that there is little role for saline and hydrocortisone in the treatment of adriamycin extravasation injury. Conclusion: In this study, we compared some treatment methods in adriamycin extravasation model. The findings support the propranolol injection may prevent extravasation injury. However this study was performed in the laboratory using rats, and the results could be different in clinical application. Thus, more needs further investigations and clinical application.

Effect of Autophagy-Related Beclin1 on Sensitivity of Cisplatin-Resistant Ovarian Cancer Cells to Chemotherapeutic Agents

  • Sun, Yang;Liu, Jia-Hua;Jin, Long;Sui, Yu-Xia;Han, Li-Li;Huang, Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2785-2791
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    • 2015
  • The purpose of the study was to determine the effects of autophagy related gene Beclin1 at different levels of expression on the sensitivity of cisplatin-resistant ovarian cancer cells (SKOV3/DDP) to different chemotherapeutics. In pSUPER-Beclin1 transfected cells, real-time fluorescence quantitative RT-PCR and Western blot analysis showed that expression was significantly inhibited. Flow cytometry revealed that the mean fluorescence intensity (MDC), reflecting autophagy, and cells in the G0/G1 phase were markedly reduced. When compared with the blank control group, inhibition of Beclin1 expression in SKOV3/DDP cells not only increased the rate of apoptosis following treatment with chemotherapeutics, but also increased the sensitivity. These findings suggest that Beclin1 expression plays an important role in chemotherapeutic agent-induced death of SKOV3/DDP cells. Inhibition of autophagy related gene Beclin1 expression in SKOV3/DDP cells may increase the rate of apoptosis and elevate the sensitivity to chemotherapeutics.

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

  • Hussain, Arif;Mohsin, Javeria;Prabhu, Sathyen Alwin;Begum, Salema;Nusri, Qurrat El-Ain;Harish, Geetganga;Javed, Elham;Khan, Munawwar Ali;Sharma, Chhavi
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.10
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    • pp.5855-5860
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    • 2013
  • Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

Harmal Extract Induces Apoptosis of HCT116 Human Colon Cancer Cells, Mediated by Inhibition of Nuclear Factor-κB and Activator Protein-1 Signaling Pathways and Induction of Cytoprotective Genes

  • Elkady, Ayman I;Hussein, Rania A;El-Assouli, Sufian M
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1947-1959
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    • 2016
  • Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Gastric Cancer

  • Park, Seul-Kee;Woo, Yang-Hee;Kim, Ho-Geun;Lee, Yong-Chan;Choi, Sung-Ho;Hyung, Woo-Jin;Noh, Sung-Hoon
    • Journal of Gastric Cancer
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    • v.10 no.4
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    • pp.155-161
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    • 2010
  • Purpose: The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer. Materials and Methods: A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index. Results: The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin. Conclusions: ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.