• 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 Yeungnam Medical Science
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• 제39권2호
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• pp.124-132
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• 2022

Background: Despite recent advances in first-line chemotherapy for advanced pancreatic cancer, standard treatment after the failure of initial chemotherapy has not been established. Hence, we aimed to retrospectively analyze the clinical characteristics and outcomes of second-line chemotherapy in patients with advanced pancreatic cancer. Methods: We reviewed the clinical data of patients with advanced pancreatic cancer who underwent palliative chemotherapy at Kosin University Gospel Hospital between January 2013 and October 2020. Results: Among 366 patients with advanced pancreatic cancer who had received palliative chemotherapy, 104 (28.4%) underwent at least one cycle of second-line chemotherapy. The median age of the patients at the time of initiating second-line treatment was 62 years (interquartile range, 57-62 years), and 58.7% (61 patients) of them were male. The common second-line chemotherapy regimens were 5-fluorouracil (FU) plus leucovorin, irinotecan, and oxaliplatin (33 patients, 31.7%); gemcitabine/nab-paclitaxel (29, 27.9%), gemcitabine±erlotinib (13, 12.5%); and oxaliplatin and 5-FU/leucovorin (12, 11.5%). The median overall survival (OS) and progression-free survival were 6.4 months (95% confidence interval [CI], 4.5-8.6 months) and 4.5 months (95% CI, 2.7-6.3 months), respectively. In a multivariate analysis, poor performance status (PS) (hazard ratio [HR], 2.247; p=0.021), metastatic disease (HR, 2.745; p=0.011), and elevated carcinoembryonic antigen (CEA) levels (HR, 1.939; p=0.030) at the beginning of second-line chemotherapy were associated with poor OS. Conclusion: The survival outcome of second-line chemotherapy for advanced pancreatic cancer remains poor. However, PS, disease extent (locally advanced or metastatic), and CEA level may help determine patients who could benefit from second-line treatment.

• 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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• 제6권1호
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• pp.40-44
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• 2018

국소적인 진행성 위암의 근치적인 치료는 수술이 첫 번째 방법이다. 하지만 위암을 진단받은 환자 중에서 약 30% 만이 수술이 가능한 진행성 위암으로 진단을 받으며 그 중 약 40-60% 만이 R0 절제술이 가능하다. 저자들은 위 주위 림프절과 복강 림프절, 장막을 침범한 진행성 위암을 진단받은 환자를 3주간의 수술 전 항암화학요법으로 치료하였고, 근치적인 목적으로 위 절제술을 시행하였다. 조직병리검사에서 완전히 괴사된 종양 조직을 관찰할 수 있었고, 수술 후 현재까지 3차례의 추가적인 전신 항암화학요법을 시행하고 있으며, 추적 복부 전산화단층촬영에서 재발을 시사하는 소견을 보이지 않았다.

• 한국간담췌외과학회지
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• 제27권2호
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• pp.141-150
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• 2023

Pancreatic carcinosarcoma is a very rare malignancy with a poor prognosis. Because of these characteristics, a treatment strategy for it has not been established yet. The aim of this study was to establish a therapeutic strategy for pancreatic carcinosarcoma. We reviewed data of a 65-year-old female patient who was diagnosed with pancreatic carcinosarcoma through endoscopic ultrasound-guided fine needle aspiration biopsy before surgery. For literature review, we searched PubMed using terms of "Pancreatic" or "Pancreas" and "carcinosarcoma" or "carcinosarcomatous". The patient received 11 cycles of neoadjuvant treatment with leucovorin, fluorouracil, irinotecan, oxaliplatin and pembrolizumab because the tumor was borderline resectable. She underwent stereotactic ablative body radiotherapy (SABR) with 35 Gy in 5 fractions, followed by robotic pylorus-preserving pancreaticoduodenectomy. After surgery, the patient received adjuvant chemotherapy in the same regimen as before surgery. She is alive without any recurrence. Among 48 patients within 33 available papers, the median survival time was 15 months. The survival rate of patients who received adjuvant chemotherapy tended to be higher than that of those who did not receive adjuvant chemotherapy, although the difference was not statistically significant (median survival, 47 vs. 15 months; p = 0.485). Three patients who received neoadjuvant chemotherapy had a survival period of 13-23.5 months. Surgery with lymphadenectomy, adjuvant therapy, and neoadjuvant therapy are thought to help improve survival outcomes. Modern treatment approaches for conventional pancreatic ductal adenocarcinoma could be applied to pancreatic carcinosarcoma.

• 한국식품영양학회지
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• 제37권3호
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• pp.139-151
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• 2024

The objective of this study was to investigate the anticancer effects of EMPS (edible mushroom mycelium polysaccharide: Tremella fuciformis) in animal models with colorectal cancer induced by AOM/DSS. The experimental groups consisted of Nor (normal), NC (AOM/DSS), EMPS (EMPS 50, EMPS 100), and PC (Fluorouracil). The NC group had the highest number of colon tumors, whereas it was observed that tumor occurrence was significantly reduced in the EMPS consumption group. The expression of Bcl-2, an apoptosis inhibitor, was significantly lower in the EMPS 50 & 100 and PC groups. On the other hand, the mRNA gene expression of Bax, a factor that induces apoptosis, was significantly higher in the EMPS 50 & 100 and PC groups compared to the NC group. The mRNA expression levels of TNF-α and COX-2 significantly increased in the NC group, but showed a significant decrease in the EMPS and PC groups, indicating inhibition of the cancer-promoting response of cells. At the phylum level of the mice's intestinal microbial composition, the proportion of Bacteroidetes tended to decrease, while the proportion of Firmicutes tended to increase with EMPS administration. This suggests that changes in the gut microbiota caused by inflammation can be influenced by dietary intake.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7179-7188
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• 2015

Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.

• Journal of Oral Medicine and Pain
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• 제30권3호
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• pp.287-300
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• 2005

두경부에서 발생하는 편평세포암종은 같은 조직학적 분류, 조직학적 단계 및 임상 단계에 있다하더라도 항암제 투여에 따른 감수성은 환자마다 다양하게 나타난다. 따라서, 본 연구의 목적은 기존에 가장 많이 사용하는 항암제인 5-FU 와 Cisplatin의 감수성을 예측할 수 있는 생물학적 표지자를 찾아 환자에게 맞는 항암제를 선택하기 위해서이다. 5종의 구강 편평암세포암주를 이용하였으며, 5-FU 와 Cisplatin의 항암제 감수성을 측정하기 위해 MTT assay를 시행하였다. 각 세포 주의 전 RNA를 추출하였으며 이어서 cDNA를 합성하였다. 다양한 유전자를 1) 돌연변이 2) 염증(COX pathway) 3) 세포주기 4) 노화 5) 세포외기질 과 관련되게 분류하였고 RT-PCR을 시행하여 유전자의 발현량을 살펴보았다. 결과물은 Scion image 프로그램을 통해 분석하였고, Sigma plot을 이용해 표시하였다. 5-FU의 감수성과 비례하는 유전자들은 XPA, XPC, OGG, APEX, COX-2, PPAR, Cyclin E, Cyclin B1, CDC2, hTERT, hTR, TIMP-3, TIMP-4 및 HSP47이었으며, Cisplatin의 감수성과 비례하는 유전자들은 COX-1, iNOS, eNOS, PCNA, Col-1 및 MMP-9 으로 알 수 있었다. 위 결과는 암환자에게 알맞은 항암제를 선택 시 항암제의 감수성과 관련한 유전자들의 발현 정도를 파악한다면 올바른 항암제를 선택하는데 도움이 되리라 사료된다.

• Radiation Oncology Journal
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• 제26권3호
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• pp.142-148
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• 2008

목 적: 조기유방암의 치료에 있어 과거에는 유방 전적출술이 주된 치료였으나 현재는 유방보존술이 표준 치료방법으로 정립되었다. 저자들은 서울대학교병원에서 유방보존수술 및 방사선치료를 받은 환자의 임상적 특성을 조사하고 치료결과 및 예후인자를 분석하고자 하였다. 대상 및 방법: 1992년 2월부터 2002년 1월까지 침윤성 유방암으로 유방보존수술 및 수술 후 방사선치료를 받은 424명을 대상으로 후향적으로 분석하였다. 대부분의 환자는 사분절제술 및 액와림프절 청소술을 시행 받았다(396명, 93.4%). 302명이 T1이었고 122명은 T2 병기였으며, 림프절 전이는 107명에서 확인되었다. 방사선치료는 전체 유방에 28회에 걸쳐 50.4 Gy를 조사한 후 종양이 있었던 부위에 10 Gy의 추가조사를 실시하였다. 영역림프절 조사는 57명에서 시행되었다. 항암화학요법은 231명에서 시행되었으며, 그 중 170명이 cyclophosphamide, methotrexate 및 5-fluorouracil을 투여 받았다. 중앙추적기간은 64개월이었다. 결 과: 전체 환자의 5년 국소제어율은 95.6%이었다. 추적관찰 중 15명의 환자에서 국소재발이 확인되었다. 5년 생존율은 93.1%이었고, 병기에 따른 5년 생존율은 I기 94.8%, IIA기 95.0%, IIB기 91.1%, IIIA기 75.9%, IIIC기 57.1%이었다. 5년 무병생존율은 88.7%이었고, 병기별로는 I기 93.1%, IIA기 89.4%, IIB기 82.8%, IIIA기 62.0%, IIIC기 28.6%이었다. 예후인자 분석에서는 N 병기(p=0.0483)가 생존율에, 연령(p=0.0284)과 N 병기(p=0.0001)가 무병생존율에 각각 유의한 영향을 보였다. 결 론: 조기유방암에서 유방보존수술 및 수술 후 방사선치료는 우수한 국소제어율 및 생존율을 기대할 수 있는 치료법임을 확인할 수 있었다.

• Journal of Gastric Cancer
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• 제5권4호
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• pp.281-287
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• 2005

목적: UICC 분류에 의한 2기 위암환자의 임상병리학적 특징에 대하여 알아보고 수술 후 보조요법으로서의 항암, 방사선 치료가 5년 생존율에 미치는 효과에 대하여 알아보고자 하였다. 대상 및 방법: UICC에 의한 병리학적 분류로 병기2기로 판정된 954명을 대상으로 하였다. 항암치료는 수술 후 3주째부터 5-Fluorouracil $400mg/m^2/day$와 Leucovorin $20mg/m^2/day$를 사용하였으며 방사선 치료는 총 4,500 cGy를 25회로 나누어 시행하였다. 결과: 임상병리학적 인자들의 생존율분석에서 환자의 나이, 수술방법, 종양의 크기와 항암 및 방사선 치료가 의미 있는 예후 인자로 분석되었다. 수술 후 항암 방사선 치료에 따른 생존율 분석에서 보조요법을 시행하지 않은 425예의 5년 생존율은 67.9%, 항암 치료 군 187예는 79.8%, 항암방사선 치료 군 342예는 83.6%로 조사되어 통계적으로 유의한 차이를 보였으며(P<0.0001) 항암치료 군과 항암방사선 치료 군과의 생존율 비교에서는 항암방사선 치료 군에서 생존율의 향상을 보여주기는 하였으나 통계적으로 유의하지는 않았다(P=0.1264). 결론: 2기 위암환자에서 환자의 나이, 수술방법, 종양의 크기 및 수술 후 보조적인 항암 및 방사선 치료가 5년 생존율에 영향을 주는 의미 있는 예후인자로 조사되었다. 수술 후 보조요법의 시행이 통계적으로 의미 있는 생존율을 보였으나 임상병리학적 인자들을 고려한 무작위 연구를 통해 그 의미를 검증해야 할 것으로 생각된다.