• Journal of Chest Surgery
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• 제56권2호
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• pp.67-74
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• 2023

Perioperative treatment with conventional cytotoxic chemotherapy for resectable non-small cell lung cancer (NSCLC) has proven clinical benefits in terms of achieving a higher overall survival (OS) rate. With its success in the palliative treatment of NSCLC, immune checkpoint blockade (ICB) has now become an essential component of treatment, even as neoadjuvant or adjuvant therapy in patients with operable NSCLC. Both pre- and post-surgery ICB applications have proven clinical efficacy in preventing disease recurrence. In addition, neoadjuvant ICB combined with cytotoxic chemotherapy has shown a significantly higher rate of pathologic regression of viable tumors compared with cytotoxic chemotherapy alone. To confirm this, an early signal of OS benefit has been shown in a selected population, with programmed death ligand 1 expression ≥50%. Furthermore, applying ICB both pre- and post-surgery enhances its clinical benefits, as is currently under evaluation in ongoing phase III trials. Simultaneously, as the number of available perioperative treatment options increases, the variables to be considered for making treatment decisions become more complex. Thus, the role of a multidisciplinary team-based treatment approach has not been fully emphasized. This review presents up-to-date pivotal data that lead to practical changes in managing resectable NSCLC. From the medical oncologist's perspective, it is time to dance with surgeons to decide on the sequence of systemic treatment, particularly the ICB-based approach, accompanying surgery for operable NSCLC.

• 한국임상약학회지
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• 제19권2호
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• pp.89-95
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• 2009

Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2000년도 춘계학술대회
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• pp.8-9
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• 2000

Despite the advances made in the past few decades in cancer chemotherapy, many conventional anticancer drugs display relatively poor selectivity for cancer cells. The nonselectivity of anticancer drugs and the development of anticancer drug resistance have been recognized as serious limitations in their clinical usefulness. Therefore, a major challenge in cancer chemotherapy is the development of new anticancer agents with improved selectivity for tumor cells as well as the prevention of the host cell resistance, both of which result in the improvement of therapeutic effect against cancer cells. Cyclophosphamide (CP), a widely used anticancer agent, is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C$_4$- hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) is converted to the ring-opened tautomer to aldophosphamide (Aldo) which subsequently undergoes a base- catalyzed ${\beta}$-elimination to generate cytotoxic phosphoramide mustard (PDA) and acrolein. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA.

• 한국자기공명학회논문지
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• 제21권1호
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• pp.31-43
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• 2017

Together with radiotherapy, chemotherapy using cytotoxic agents is one of the most common therapies in cancer. Metabolic changes in cancer cells are drawing much attention recently, but the metabolic alterations by anticancer agents have not been much studied. Here, we investigated the effects of commonly used cytotoxic agents on lung normal cell MRC5 and lung cancer cell A549. We employed cis-plastin, doxorubicin, and 5-Fluorouracil and compared their effects on the viability and metabolism of the normal and cancer cell lines. We first established the concentration of the cytotoxic reagents that give differences in the viabilities of normal and cancer cell lines. In those conditions, the viability of A549 decreased significantly, whereas that of MRC5 remained unchanged. To study the metabolic alterations implicated in the viability differences, we obtained the metabolic profiles using $^1H$-NMR spectrometry. The $^1H$-NMR data showed that the metabolic changes of A549 cells are more remarkable than that of MRC5 cells and the effect of 5-FU on the A549 cells is the most distinct compared to other treatments. Heat map analysis showed that metabolic alterations under treatment of cytotoxic agents are totally different between normal and cancer cells. Multivariate analysis and weighted correlation network analysis (WGCNA) revealed a distinctive metabolite signature and hub metabolites. Two different analysis tools revealed that the changes of cell metabolism in response to cytotoxic agents were highly correlated with the Warburg effect and Reductive lipogenesis, two pathways having important effects on the cell survival. Taken together, our study addressed the correlation between the viability and metabolic profiles of MRC5 and A549 cells upon the treatment of cytotoxic anticancer agents.

• Journal of Korean Biological Nursing Science
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• 제4권2호
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• pp.69-77
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• 2002

The purpose of this study was to identify the relationship of symptom distress and natural killer cell cytotoxicity in breast cancer patients who had been radiation therapy and/or chemotherapy after surgery. Symptom distress measured by modified Lee's(1994) physical symptom questionnaire. For measuring the natural killer cell cytotoxic activity. 8ml to 10ml blood was collected from the subjects. Mononuclear cell was isolated by centrifuge of the blood and cultured by putting $Cr^{51}$, and reacted with target cell, K562 cell. Amount of $Cr^{51}$ was measured, and %lysis was calculated. The results were as follows. 1) Symptom distress score was 42.18, which is moderate symptom distress. 2) Natural killer cell cytotoxic activities were 42.18%lysis(effector : target cell ratio=100 : 1) and 28.05%lysis(effector : target cell ratio=50 : 1). 3) Correlation coefficients of symptom distress and natural killer cell cytotoxic activity were $-.134{\sim}-.461$. Though significant correlation was not found between total score of symptom distress and natural killer cell cytotoxic activity, 3('pain' 'feel hot on radiation site' and 'difficulty in breathing') of 19 symptom distress items and natural killer cell cytotoxic activity showed significant negative correlation(p<.05). These findings suggest that 1) breast cancer patients who had been radiation therapy and/or chemotherapy after surgery have moderate symptom distress and decreased natural killer cell cytotoxic activity. 2) The symptom distress was not related to natural killer cell cytotoxic activity.

• Archives of Pharmacal Research
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• 제22권4호
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• pp.380-383
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• 1999

Five 1-azzanthraquinone-3-carboxamides were synthesized and evaluated in vitro cytotoxicity against four human cancer cell lines. The most active compound, 7b, exhibited cytotoxic activity comparable to doxorubicin.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7645-7649
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• 2013

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

• Tuberculosis and Respiratory Diseases
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• 제82권3호
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• pp.179-189
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• 2019

Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

• 대한의생명과학회지
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• 제25권4호
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• pp.293-301
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• 2019

Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.167.2-168
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• 2003

Anticancer drug resistance occasionally occurs in malignant hematologic diseases such as acute myelocytic leukemia (AML) treated with chemotherapy and is a major problem to complete remission. Malignant cells primarily induce intrinsic resistance to treatment of anticancer drug, but gradually obtain acquired resistance to cytotoxic activities of chemotherapy. In this study, we monitored the expression profiles of doxorubicin resistance-related genes in AML-2/DX100, a doxorubicin-resistant human acute myelocytic leukemia cell line. (omitted)