• International Journal of Oral Biology
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• 제46권4호
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• pp.176-183
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• 2021

Oral squamous cell carcinoma (OSCC) metastasis is characterized by distant metastasis and local recurrence. Combined chemotherapy with cisplatin and 5-fluorouracil is routinely used to treat patients with OSCC, and the combined use of gefitinib with cytotoxic drugs has been reported to enhance the sensitivity of cancer cells in vitro. However, the development of drug resistance because of prolonged chemotherapy is inevitable, leading to a poor prognosis. Therefore, understanding alterations in signaling pathways and gene expression is crucial for overcoming the development of drug resistance. However, the altered characterization of Ca²⁺ signaling in drug-resistant OSCC cells remains unclear. In this study, we investigated alterations in intracellular Ca²⁺ ([Ca²⁺]_i) mobilization upon the development of gefitinib resistance in human tongue squamous carcinoma cell line (HSC)-3 and HSC-4 using ratiometric analysis. This study demonstrated the presence of altered epidermal growth factor- and purinergic agonist-mediated [Ca²⁺]_i mobilization in gefitinib-resistant OSCC cells. Moreover, Ca²⁺ content in the endoplasmic reticulum, store-operated calcium entry, and lysosomal Ca²⁺ release through the transient receptor potential mucolipin 1, were confirmed to be significantly reduced upon the development of apoptosis resistance. Consistent with [Ca²⁺]_i mobilization, we identified modified expression levels of Ca²⁺ signaling-related genes in gefitinib-resistant cells. Taken together, we propose that the regulation of [Ca²⁺]_i mobilization and related gene expression can be a new strategy to overcome drug resistance in patients with cancer.

• Journal of Gastric Cancer
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• 제23권1호
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• pp.207-223
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• 2023

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

• Journal of Digestive Cancer Research
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• 제1권1호
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• pp.36-42
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• 2013

배경 및 목적: Gemcitabine은 진행성 췌장암 환자의 치료에 우선적으로 사용되며, 다른 항암 약제에 비하여 상대적으로 독성이 적은 것으로 알려져 있다. 그러나 약제의 낮은 반응률과 상대적으로 높은 합병증의 발생률 때문에 많은 소화기암을 다루는 의사들은 췌장암을 가진 노인환자에서 항암치료를 꺼려하는 경항이 있다. 방법: 2007년에서 2010년 사이에 조직학적으로 췌장암을 진단받고, gemcitabine 항암요법을 시행받은 61명의 환자를 후향적으로 임상적, 검사실 및 영상학적 자료를 분석하였다. 환자는 65세 이상군 28명과 65세 미만군 38명으로 나누었다. Gemcitabine은 체표면적당 1,000 mg을 3주 동안 매주 30분에 걸쳐 투여하였고, 다른 항암제인 cisplatin, capecitabine, erlotinib 등을 병합 투여한 경우가 있었다. 결과: 환자의 평균 나이는 65세 이상군에서 71세, 65세 미만군에서 56세 였다. 진단 시 시행한 CA 19-9을 포함한 검사실검사는 두 군 간에 차이가 없었으며, gemcitabine 단독 항암요법을 시행한 경우는 65세 이상군에서 더 많았고(56.5 vs. 26.3%, p=0.029), 2차 혹은 3차 항암요법을 시행한 군은 65세 미만군에서 더 많았다(17.4 vs. 50.0%, p=0.014). 담관염이나 담관스텐트 유치는 양군에서 차이가 없었다. 결과: Gemcitabine 항암화학요법은 진행성 췌장암을 가진 노인환자에서 안전하게 사용할 수 있으며, 젊은 환자들에 견줄만한 치료 반응률과 무진행생존기간을 기대할 수 있을 것으로 예상된다.

• Toxicological Research
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• 제25권4호
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• pp.181-188
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• 2009

Uncontrolled cell growth and increased cell proliferation are major features of cancer that are dependent on the stable structure and dynamics of the cytoskeleton. Since stable cytoskeleton structure and dynamics are partly regulated by myosin light chain kinase (MLCK), many current studies focused on MLCK inhibition as a chemotherapeutic target. As a potent and selective MLCK inhibitor, ML-7 [1-(5-iodonaphthalene-1-sulfonyl)-1 H-hexahydro-1,4-diazapine hydrochloride] is a promising candidate for an anticancer agent, which would induce apoptosis as well as prevents invasion and metastasis in certain types of cancer cells. This study assessed cytotoxic effects of ML-7 against HL-60 cells and therapeutic efficacy of ML-7 as a potential antileukemia agent. Trypan-blue exclusion assays showed dose- and time- dependent decreases in ML-7 treated HL-60 cells (p<0.05). Comet assays revealed a significant increase in DNA damage in HL-60 cells after treatment with $40{\mu}M$ ML-7 for 2h. Sub-G1 fractions, analyzed by flow cytometry increased in a dose-dependent manner, suggesting that ML-7 can induce apoptotic cell death in HL-60 cells. ML-7 was selectively cytotoxic towards HL-60 cells; not affecting normal human lymphocytes. That selective effect makes it a promising potential anti-leukemia agent. In addition, anticancer efficacy of ML-7 in combination with flavonoids (genistein or quercetin) or anticancer drugs (cisplatin or Ara-C) against HL-60 cells was assessed. Combination of ML-7 with flavonoids increased the anti-cancer effect of ML-7 to a greater extent than combination with the anticancer drugs. This implies that ML-7 in combination with flavonoids could increase the efficacy of anticancer treatment, while avoiding side effects cansed by conventional anticancer drug-containing combination chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2771-2774
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• 2012

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

• Journal of Gastric Cancer
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• 제24권3호
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• pp.246-256
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• 2024

Purpose: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. Materials and Methods: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. Results: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. Conclusions: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.

• Asian Pacific Journal of Cancer Prevention
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• 제17권10호
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• pp.4755-4759
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• 2016

Introduction: Lung cancer is one of the most common cancers worldwide. In certain countries such as United States of America, it is the leading cause of related cancer mortality among both men and women. Natural products play an important role in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In this study, we investigated the antiproliferative and apoptotic activities of Kanahia laniflora methanolic extract against human non-small cell lung cancer cells (A549). Methods: Sulforhodamine B colorimetric assays were used to determine the inhibitory effects of a leaf methanolic extract against A549 cells. Results: The extract showed strong cytotoxic activity against A549 cells with an $IC_{50}$ value of $0.13{\mu}g/ml$ compared to $0.21{\mu}g/ml$ for doxorubicin. The extract also significantly increased the percentage of apoptotic cells to 49.7% as compared to 1.4% and 47.4% for control and doxorubicin respectively. Conclusion: These results showed, for the first time, that a methanolic extract of Kanahia laniflora leaves can inhibit the proliferation of human non-small cell lung cancer cells (A549). Further attention to its potential as a new effective anticancer agent is warranted.

• Clinical and Experimental Reproductive Medicine
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• 제44권4호
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• pp.187-192
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• 2017

Although the survival rate of hematologic malignancies in young patients is very high, cytotoxic therapies such as chemotherapy and total body irradiation therapy can significantly reduce a patient's reproductive capacity and cause irreversible infertility. Early ovarian failure also commonly occurs following additional cancer treatment, bone marrow transplantation, or autologous transplantation. Because the risk of early ovarian failure depends on the patient's circumstances, patients with a hematologic malignancy must consult health professionals regarding fertility preservation before undergoing treatments that can potentially damage their ovaries. While it is widely known that early menopause commonly occurs following breast cancer treatment, there is a lack of reliable study results regarding fertility preservation during hematologic malignancy treatment. Therefore, an in-depth discussion between patients and health professionals about the pros and cons of the various options for fertility preservation is necessary. In this study, we review germ cell toxicity, which occurs during the treatment of hematologic malignancies, and propose guidelines for fertility preservation in younger patients with hematologic malignancies.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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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.

• Radiation Oncology Journal
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• 제28권2호
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• pp.106-110
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• 2010

B형 간염바이러스의 재활성화는 세포독성치료 및 면역억제치료를 시행 받은 만성 B형 간염 환자 및 보균자들에서 잘 알려진 합병증이다. 방사선치료의 경우, B형 간염바이러스 재활성화에 대한 연구는 그 수가 적으며, 대개 이전에 항암화학요법 또는 경동맥화학색전술을 시행 받은 환자를 포함한다. 간의 방사선조사만을 시행 받은 환자에서의 B형 간염바이러스의 재활성화에 대한 연구는 보고된 바 없으며, 이에 본 증례를 보고한다. 본 연구를 통하여, 간의 국소방사선조사 단독으로 B형 간염바이러스의 재활성화 유발의 가능성을 확인하였으며, 따라서, 간을 포함한 방사선조사 시 B형 간염관련 간질환 환자의 경우 방사선 관련 간질환뿐 아니라 바이러스의 재활성화에 대한 고려도 요구된다.