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1.
Cancer Manag Res ; 16: 1131-1139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247180

RESUMO

Purpose: The COVID-19 pandemic has influenced various aspects of colorectal cancer (CRC) patient care, including diagnosis, treatment, and outcomes. This study assesses the pandemic's impact on CRC patients. Methods: We performed a retrospective analysis of medical records for CRC patients who underwent surgery at five hospitals affiliated with Hallym University from January 2017 to December 2022. Patients were divided into two groups: the pre-COVID group (2017-2019) and the COVID group (2020-2022). Results: Among 2038 patients, 987 (48.4%) were in the pre-COVID group, and 1051 (51.6%) were in the COVID group. The COVID group had more patients with two or more comorbidities (P < 0.001) and a higher incidence of rectal cancer (P = 0.010). While the rates of laparoscopic surgeries were similar, the COVID group had increased emergency surgeries (P = 0.005) and diversion procedures (P = 0.002). Additionally, the COVID group faced more overall complications (P < 0.001) and severe complications (Grade III-V, P = 0.004). There was a rise in lymphovascular invasion (P < 0.001) and T4 stage tumors (P < 0.001) within the COVID group. Despite these differences, both groups had similar 2-year overall survival rates (P = 0.409). Conclusion: Although patients treated during the COVID period experienced more frequent stoma formation, complications, and adverse prognostic factors, there were no differences in short-term oncologic outcomes, which was likely due to the follow-up period being insufficient to detect differences in OS.

2.
Cancer Diagn Progn ; 4(5): 563-566, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39238628

RESUMO

Background/Aim: Transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP) were previously developed by our laboratory, AntiCancer Inc. In the present study, we demonstrate imaging of the GFP, RFP, or CFP nude mice with single-nanometer-tuning laser fluorescence excitation with a single instrument. Materials and Methods: Female transgenic C57/B6 nude GFP, RFP, and CFP mice aged six weeks were used. The images were obtained using the UVP Biospectrum Advanced system (Analytik Jena US LLC) with excitation at 480 nm and peak emission at 513 nm for GFP; 520 nm and 605 nm, respectively, for RFP; and 405 nm and 480 nm, respectively, for CFP. Results: For each color transgenic fluorescent mouse, images without background could be obtained individually with the UVP Biospectrum Advanced system. Conclusion: Using a single instrument, brilliant and well-defined images of GFP, RFP, and CFP mice were obtained with single-nanometer-tuning laser fluorescence excitation. This imaging system will be used in future studies to analyze cancer cells in the colored mice that are spectrally distinct in order to determine how stromal cells and cancer interact in the tumor microenvironment.

3.
In Vivo ; 38(5): 2122-2125, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39187316

RESUMO

BACKGROUND/AIM: In vivo imaging with luciferase-luciferin has been limited by the inability to visualize the low emitted light, with the signal quantified only by photon counting using a cumbersome highly-cooled CCD camera in a dark room. In the present study, we demonstrate direct visualization of the luciferase-luciferin signal from an orthotopic lung cancer in a nude-mouse xenograft model with a sensitive low-light camera and optics. MATERIALS AND METHODS: Mouse Lewis-lung carcinoma cells expressing luciferase (LL/2-Luc2) were injected transcutaneously into the lung of a nude mouse. One week later after cell injection, luciferase imaging for emission at 560 nm was performed using the UVP Biospectrum Advanced system after i.v. injection of D-luciferin potassium salt. The intensity of the visualized light was measured and quantified with the instrument. RESULTS: A week following the implantation of LL/2-Luc2 cells in nude mice, the luciferase-luciferin signal from LL/2-Luc2 tumors in the lung was sufficiently visible through the skin to produce true images. At fifteen minutes, the intensity peaked and then progressively dropped due to clearance of luciferin from the tumor. CONCLUSION: Using the UVP Biospectrum Advanced system we demonstrated non-invasive visualization of true images from luciferase-luciferin signals from an orthotopic lung-cancer mouse model. The luciferase-luciferin emitted light was directly visible through the skin which is a major improvement over previous photon counting to detect the luciferase-luciferin signal.


Assuntos
Luciferases , Medições Luminescentes , Neoplasias Pulmonares , Camundongos Nus , Animais , Camundongos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico por imagem , Luciferases/metabolismo , Luciferases/genética , Linhagem Celular Tumoral , Medições Luminescentes/métodos , Modelos Animais de Doenças , Humanos , Xenoenxertos , Benzotiazóis , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Anticancer Res ; 44(9): 3885-3889, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197890

RESUMO

BACKGROUND/AIM: Pancreatic cancer has a very poor prognosis with a 5-year survival rate of less than 5% among patients with distant metastasis, a figure that has not improved over many decades. Only 10 to 20% patients are candidates for curative surgery at presentation due to the aggressive nature and asymptomatic progression of pancreatic cancer. Although first-line chemotherapy, such as FOLFIRINOX and gemcitabine + nab paclitaxel, improved the median survival from 8.5 to 11.1 months, more effective treatments are immediately needed. The aim of the present study was to evaluate the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet combined with first-line chemotherapy on a patient with stage IV metastatic pancreatic cancer. CASE REPORT: A 63-year-old female was diagnosed with metastatic pancreatic cancer in October 2023. The patient started FOLFIRINOX as first-line chemotherapy in combination with methionine restriction, which comprised o-rMETase 250 units twice a day and a low-methionine diet. The patient was monitored using computed tomography and CA19-9 blood tests. After five months from the start of combination therapy, the size of the primary tumor decreased by 40% along with liver-metastasis regression. The CA19-9 blood marker decreased by 86%. The patient sustains a high performance status and continues the combination therapy without severe side effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with first-line chemotherapy, was highly effective in a patient with inoperable stage IV pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Liases de Carbono-Enxofre , Metionina , Neoplasias Pancreáticas , Humanos , Feminino , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/sangue , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Metionina/administração & dosagem , Estadiamento de Neoplasias , Biomarcadores Tumorais/sangue , Fluoruracila/administração & dosagem , Antígeno CA-19-9/sangue , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Administração Oral
5.
Anticancer Res ; 44(9): 3891-3898, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197923

RESUMO

BACKGROUND/AIM: Positron emission tomography (PET) is an important imaging modality, especially in oncology. [18F]fluorodeoxyglucose PET (FDG-PET) is the most used cancer PET imaging. However, since the elevated glucose use by cancers, termed the Warburg effect, is usually only moderate, FDG often does not provide a strong or well-delineated signal. Malignancies have a stronger addiction to methionine, known as the Hoffman effect, and thus [11C]methionine PET (MET-PET) has demonstrated superiority over FDG-PET in gliomas and other brain tumors. Our team is pioneering the use of MET-PET for tumors of the trunk for both better detection of cancer and to determine candidates for methionine-restriction therapy. The present study provides examples of cancers of organs in the trunk in which MET-PET outperforms FDG-PET in detecting and delineating primary and metastatic cancer. PATIENTS AND METHODS: In all cases, MET-PET and FDG-PET were performed simultaneously. An evaluation of the images was conducted by a nuclear medicine physician. RESULTS: Four cases, including prostate, bladder, esophageal, and breast cancer demonstrated the superiority of MET-PET compared to FDG-PET. CONCLUSION: MET-PET can out-perform FDG PET for accurate detection of primary and metastatic cancer in the trunk and can determine the extent of methionine addiction of cancer, thereby indicating whether cancer patients can benefit from methionine-restriction therapy.


Assuntos
Fluordesoxiglucose F18 , Metionina , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Imagem Corporal Total , Humanos , Tomografia por Emissão de Pósitrons/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Imagem Corporal Total/métodos , Glucose/metabolismo , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Metástase Neoplásica , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Radioisótopos de Carbono
6.
Anticancer Res ; 44(9): 3777-3783, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197933

RESUMO

BACKGROUND/AIM: A major challenge in treating soft-tissue sarcoma is the development of drug resistance. Eribulin, an anti-tubulin agent, is used as a second-line chemotherapy for patients with unresectable or metastatic soft-tissue sarcoma. However, most patients with advanced soft-tissue sarcoma are resistant to eribulin and do not survive. Recombinant methioninase (rMETase) targets the fundamental and general hallmark of cancer, methionine addiction, termed the Hoffman Effect. The present study aimed to show how much rMETase could increase the efficacy of eribulin on eribulin-resistant fibrosarcoma cells in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells were exposed to step-wise increasing concentrations of eribulin from 0.15-0.4 nM to establish eribulin-resistant HT1080 (ER-HT1080). ER-HT1080 cells were cultured in vitro and divided into four groups: untreated control; eribulin treated (0.15 nM); rMETase treated (0.75 U/ml); and eribulin (0.15 nM) plus rMETase (0.75 U/ml) treated. RESULTS: The IC50 of eribulin on ER-HT1080 cells was 0.95 nM compared to the IC50 of 0.15 nM on HT1080 cells, a 6-fold increase. The IC50 of rMETase on ER-HT1080 and HT1080 was 0.87 U/ml and 0.75 U/ml, respectively. The combination of rMETase (0.75 U/ml) and eribulin (0.15 nM) was synergistic on ER-HT1080 cells resulting in an inhibition of 80.1% compared to eribulin alone (5.0%) or rMETase alone (47.1%) (p<0.05). rMETase thus increased the efficacy of eribulin 16-fold on eribulin-resistant fibrosarcoma cells. CONCLUSION: The present study showed that the combination of eribulin and rMETase can overcome high eribulin resistance of fibrosarcoma. The present results demonstrate that combining rMETase with first- or second-line therapy for soft-tissue sarcoma has the potential to overcome the intractable clinical problem of drug-resistant soft-tissue sarcoma.


Assuntos
Liases de Carbono-Enxofre , Resistencia a Medicamentos Antineoplásicos , Fibrossarcoma , Furanos , Cetonas , Humanos , Cetonas/farmacologia , Furanos/farmacologia , Liases de Carbono-Enxofre/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Linhagem Celular Tumoral , Proteínas Recombinantes/farmacologia , Antineoplásicos/farmacologia , Sinergismo Farmacológico , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Policetídeos de Poliéter
7.
Anticancer Res ; 44(8): 3261-3268, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060039

RESUMO

BACKGROUND/AIM: Doxorubicin is first-line therapy for soft-tissue sarcoma, but patients can develop resistance which is usually fatal. As a novel therapeutic strategy, the present study aimed to determine the synergy of recombinant methioninase (rMETase) and doxorubicin against HT1080 fibrosarcoma cells compared to Hs27 normal fibroblasts, and rMETase efficacy against doxorubicin-resistant HT1080 cells in vitro. MATERIALS AND METHODS: The 50% inhibitory concentrations (IC50) of doxorubicin and rMETase, as well as their combination efficacy, against HT1080 human fibrosarcoma cells, Hs27 normal human fibroblasts and doxorubicin-resistant HT1080 (DR-HT1080) cells were determined. Dual-color HT1080 cells which expressed red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize nuclear fragmentation during treatment. Nuclear fragmentation was observed with an IX71 fluorescence microscope. RESULTS: The IC50 for doxorubicin was 3.3 µM for HT1080 cells, 12.4 µM for DR-HT1080 cells, and 7.25 µM for Hs27 cells. The IC50 for rMETase was 0.75 U/ml for HT1080 cells, 0.42 U/ml for DR-HT1080 cells, and 0.93 U/ml for Hs27 cells. The combination of rMETase and doxorubicin was synergistic against fibrosarcoma cells but not against normal fibroblasts. The combination of doxorubicin plus rMETase also caused more fragmented nuclei than either treatment alone in HT1080 cells. rMETase alone was highly effective against the DR-HT1080 cells as well as the parental HT1080 cells. CONCLUSION: The present results indicate the future clinical potential of rMETase in combination with doxorubicin for fibrosarcoma, including doxorubicin-resistant fibrosarcoma.


Assuntos
Liases de Carbono-Enxofre , Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Fibrossarcoma , Proteínas Recombinantes , Humanos , Doxorrubicina/farmacologia , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Fibrossarcoma/metabolismo , Liases de Carbono-Enxofre/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas Recombinantes/farmacologia , Antibióticos Antineoplásicos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo
8.
Cancer Diagn Progn ; 4(4): 402-407, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962551

RESUMO

Background/Aim: Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and is a recalcitrant disease. Docetaxel is the first-line treatment for AIPC, but has limited efficacy and severe side-effects. All cancers are methionine-addicted, which is termed the Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of the present study was to determine if the combination of docetaxel and rMETase is effective for AIPC. Materials and Methods: The half-maximal inhibitory concentrations (IC50) of docetaxel and rMETase alone were determined for the human AIPC cell line PC-3 and Hs27 normal human fibroblasts in vitro. The synergistic efficacy for PC-3 and Hs27 using the combination of docetaxel and rMETase at their IC50s for PC-3 was determined. Results: The IC50 of docetaxel for PC-3 and for Hs27 was 0.72 nM and 0.94 nM, respectively. The IC50 of rMETase for PC-3 and for Hs27 was 0.67 U/ml and 0.76 U/ml, respectively. The combination of docetaxel and rMETase was synergistic for PC-3 but not Hs27 cells. Conclusion: The combination of a relatively low concentration of docetaxel and rMETase was synergistic and effective for AIPC. The present results also suggest that the effective concentration of docetaxel can be reduced by using rMETase, which may reduce toxicity. The present results also suggest the future clinical potential of the combination of docetaxel and rMETase for AIPC.

9.
Cancer Genomics Proteomics ; 21(4): 395-398, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38944421

RESUMO

BACKGROUND/AIM: It has been recently demonstrated that a methionine-restricted diet increases the response to immune checkpoint inhibitors (ICIs) via an increase in PD-L1 in a syngeneic mouse colorectal-cancer model. Our laboratory has developed recombinant methioninase (rMETase) to restrict methionine. The aim of the present study was to determine if rMETase can increase PD-L1 expression in a human colorectal cancer cell line in vitro. MATERIALS AND METHODS: We evaluated the half-maximal inhibitory concentration (IC50) value of rMETase on HCT-116 human colorectal cancer cells. HCT-116 cells were treated with rMETase at the IC50 Western immunoblotting was used to compare PD-L1 expression in HCT-116 cells treated with and without rMETase. RESULTS: The IC50 value of rMETase on HCT-116 was 0.79 U/ml. Methionine restriction using rMETase increased PD-L1 expression compared to the untreated control (p<0.05). CONCLUSION: Methionine restriction with rMETase up-regulates PD-L1 expression in human colorectal cancer cells and the combination of rMETase and ICIs may have the potential to improve immunotherapy in human colorectal cancer.


Assuntos
Antígeno B7-H1 , Liases de Carbono-Enxofre , Neoplasias Colorretais , Metionina , Proteínas Recombinantes , Humanos , Liases de Carbono-Enxofre/metabolismo , Metionina/farmacologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Proteínas Recombinantes/farmacologia , Células HCT116
10.
Anticancer Res ; 44(7): 2823-2826, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38925805

RESUMO

BACKGROUND/AIM: Genetic reporters encoding fluorescent proteins or luciferase have been used in vivo for the last three decades with claims about their superiority or inferiority over each other. In the present report, a head-to-head in vivo comparison of green fluorescent protein (GFP) fluorescence imaging and luciferase-luciferin imaging, using single-nanometer laser-excitation tuning of fluorescence excitation and an ultra-low-light-detection camera and optics was performed. MATERIALS AND METHODS: Mouse Lewis-lung carcinoma cells labeled with GFP (LLC-GFP) or luciferase (LL/2-Luc2) were injected subcutaneously into the flank of nude mice. One week after injection, GFP-fluorescence imaging and luciferase-luciferin imaging was performed using the UVP Biospectrum Advanced system with excitation at 487 nm and peak emission at 513 nm for GFP, and with emission at 560 nm for luciferase-luciferin. GFP fluorescence images were obtained at 0, 10, and 20 min. Luciferase-luciferin images were obtained 10 and 20 min after the injection of D-luciferin. RESULTS: The intensity of GFP images was 55,909 at 0 min, 56,186 at 10 min, and 57,085 at 20 min, and maintained after 20 min. The intensity of luciferase-luciferin images was 28,065 at 10 min after the injection of D-luciferin and 5,199 at 20 min after the injection. The intensity of luciferase-luciferin images decreased by approximately 80% at 20 min compared to 10 min. An exposure time of 30 s for luciferase-luciferin imaging was needed compared to 100 ms for GFP fluorescence imaging in order to detect signals. CONCLUSION: An imaging system with single-nanometer tuning fluorescence excitation and an ultra-low-light detection camera and optics was able to directly visualize both GFP and luciferase-luciferin images in vivo. The intensity and stability of the signals were both greater for GFP than for luciferase-luciferin, and the exposure time for GFP was 300 times faster, demonstrating the superiority of GFP.


Assuntos
Proteínas de Fluorescência Verde , Luciferases , Camundongos Nus , Animais , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Luciferases/metabolismo , Luciferases/genética , Imagem Óptica/métodos , Linhagem Celular Tumoral , Lasers , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/diagnóstico por imagem , Carcinoma Pulmonar de Lewis/patologia , Benzotiazóis , Medições Luminescentes/métodos
11.
Anticancer Res ; 44(6): 2359-2367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821601

RESUMO

BACKGROUND/AIM: The alkylating agent trabectedin, which binds the minor groove of DNA, is second-line therapy for soft-tissue sarcoma but has only moderate efficacy. The aim of the present study was to determine the synergistic efficacy of recombinant methioninase (rMETase) and trabectedin on fibrosarcoma cells in vitro, compared with normal fibroblasts. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm and Hs27 normal human fibroblasts, were used. Each cell line was cultured in vitro and divided into four groups: no-treatment control; trabectedin treated; rMETase treated; and trabectedin plus rMETase treated. The dual-color HT1080 cells were used to quantitate nuclear fragmentation in each treatment group. RESULTS: The combination of rMETase and trabectedin was highly synergistic to decrease HT1080 cell viability. In contrast, there was no synergy on Hs27 cells. Moreover, nuclear fragmentation occurred synergistically with the combination of trabectedin and rMETase on dual-color HT1080 cells. CONCLUSION: The combination treatment of trabectedin plus rMETase was highly synergistic on fibrosarcoma cells in vitro suggesting that the combination can improve the outcome of trabectedin alone in future clinical studies. The lack of synergy of rMETase and trabectedin on normal fibroblasts suggests the combination is not toxic to normal cells. Synergy of the two drugs may be due to the high rate of nuclear fragmentation on treated HT1080 cells, and the late-S/G2 cell-cycle block of cancer cells by rMETase, which is a target for trabectedin. The results of the present study suggest the future clinical potential of the combination of rMETase and trabectedin for soft-tissue sarcoma.


Assuntos
Liases de Carbono-Enxofre , Sobrevivência Celular , Dioxóis , Sinergismo Farmacológico , Fibroblastos , Fibrossarcoma , Tetra-Hidroisoquinolinas , Trabectedina , Humanos , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/patologia , Fibrossarcoma/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Trabectedina/farmacologia , Liases de Carbono-Enxofre/farmacologia , Liases de Carbono-Enxofre/administração & dosagem , Tetra-Hidroisoquinolinas/farmacologia , Dioxóis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Proteínas Recombinantes/farmacologia , Linhagem Celular Tumoral , Antineoplásicos Alquilantes/farmacologia , Núcleo Celular/metabolismo , Núcleo Celular/efeitos dos fármacos
12.
In Vivo ; 38(3): 1459-1464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688589

RESUMO

BACKGROUND/AIM: Gliomas are the most common and recalcitrant malignant primary brain tumors. All cancer types are addicted to methionine, which is a fundamental and general hallmark of cancer known as the Hoffman effect. Particularly glioma cells exhibit methionine addiction. Because of methionine addiction, [11C]-methionine positron emission tomography (MET-PET) is widely used for glioma imaging in clinical practice, which can monitor the extent of methionine addiction. Methionine restriction including recombinant methioninase (rMETase) and a low-methionine diet, has shown high efficacy in preclinical models of gliomas, especially in combination with chemotherapy. The aim of the present study was to determine the efficacy of methionine restriction with oral rMETase (o-rMETase) and a low-methionine diet, combined with radiation and temozolomide (TMZ), on a teenage female patient with high-grade glioma. CASE REPORT: A 16-year-old girl was diagnosed with high-grade glioma. Magnetic resonance imaging (MRI) showed a left temporal-lobe tumor with compression to the left lateral ventricle and narrowing of sulci in the left temporal lobe. After the start of methionine restriction with o-rMETase and a low-methionine diet, along with TMZ combined with radiotherapy, the tumor size shrunk at least 60%, with improvement in the left lateral ventricle and sulci. The patient's condition remains stable for 19 months without severe adverse effects. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with radiation and TMZ as first-line chemotherapy, were highly effective in a patient with high-grade glioma.


Assuntos
Liases de Carbono-Enxofre , Glioma , Metionina , Temozolomida , Humanos , Feminino , Glioma/patologia , Glioma/tratamento farmacológico , Glioma/terapia , Temozolomida/administração & dosagem , Temozolomida/uso terapêutico , Metionina/administração & dosagem , Adolescente , Imageamento por Ressonância Magnética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Resultado do Tratamento , Gradação de Tumores , Tomografia por Emissão de Pósitrons , Proteínas Recombinantes/administração & dosagem , Terapia Combinada
13.
JAMA Surg ; 159(7): 737-746, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656413

RESUMO

Importance: Surgical site infections (SSIs) are prevalent hospital-acquired infections with significant patient impacts and global health care burdens. The World Health Organization recommends using wound protector devices in abdominal surgery as a preventive measure to lower the risk of SSIs despite limited evidence. Objective: To examine the efficacy of a dual-ring, plastic wound protector in lowering the SSI rate in open gastrointestinal (GI) surgery irrespective of intra-abdominal contamination levels. Design, Setting, and Participants: This multicenter, patient-blinded, parallel-arm randomized clinical trial was conducted from August 2017 to October 2022 at 13 hospitals in an academic setting. Patients undergoing open abdominal bowel surgery (eg, for bowel perforation) were eligible for inclusion. Intervention: Patients were randomized 1:1 to a dual-ring, plastic wound protector to protect the incision site of the abdominal wall (experimental group) or a conventional surgical gauze (control group). Main Outcomes and Measures: The primary end point was the rate of SSI within 30 days of open GI surgery. Results: A total of 458 patients were randomized; after 1 was excluded from the control group, 457 were included in the intention-to-treat analysis (mean [SD] age, 58.4 [12.1] years; 256 [56.0%] male; 341 [74.6%] with a clean-contaminated wound): 229 in the wound protector group and 228 in the surgical gauze group. The overall SSI rate in the intention-to-treat analysis was 15.7% (72 of 458 patients). The SSI rate for the wound protector was 10.9% (25 of 229 patients) compared with 20.5% (47 of 229 patients) with surgical gauze. The wound protector significantly reduced the risk of SSI, with a relative risk reduction (RRR) of 46.81% (95% CI, 16.64%-66.06%). The wound protector significantly decreased the SSI rate for clean-contaminated wounds (RRR, 43.75%; 95% CI, 3.75%-67.13%), particularly for superficial SSIs (RRR, 42.50%; 95% CI, 7.16%-64.39%). Length of hospital stay was similar in both groups (mean [SD], 15.2 [10.5] vs 15.3 [10.2] days), as were the overall postoperative complication rates (20.1% vs 18.8%). Conclusions and Relevance: This randomized clinical trial found a significant reduction in SSI rates when a plastic wound protector was used during open GI surgery compared with surgical gaze, supporting the World Health Organization recommendation for use of wound protector devices in abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03170843.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Idoso , Plásticos , Bandagens , Método Simples-Cego
14.
In Vivo ; 38(3): 1058-1063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688611

RESUMO

BACKGROUND/AIM: Colorectal cancer (CRC) is the third-leading cause of death in the world. Although the prognosis has improved due to improvement of chemotherapy, metastatic CRC is still a recalcitrant disease, with a 5-year survival of only 13%. Irinotecan (IRN) is used as first-line chemotherapy for patients with unresectable CRC. However, there are severe side effects, such as neutropenia and diarrhea, which are dose-limiting. We have previously shown that methionine restriction (MR), effected by recombinant methioninase (rMETase), lowered the effective dose of IRN of colon-cancer cells in vitro. The aim of the present study was to evaluate the efficacy of the combination of low-dose IRN and MR on colon-cancer in nude mice. MATERIALS AND METHODS: HCT-116 colon-cancer cells were cultured and subcutaneously injected into the flank of nude mice. After the tumor size reached approximately 100 mm3, 18 mice were randomized into three groups; Group 1: untreated control on a normal diet; Group 2: high-dose IRN on a normal diet (2 mg/kg, i.p.); Group 3: low-dose IRN (1 mg/kg i.p.) on MR effected by a methionine-depleted diet. RESULTS: There was no significant difference between the control mice and the mice treated with high-dose IRN, without MR. However, low-dose IRN combined with MR was significantly more effective than the control and arrested colon-cancer growth (p=0.03). Body weight loss was reversible in the mice treated by low-dose IRN combined with MR. CONCLUSION: The combination of low-dose IRN and MR acted synergistically in arresting HCT-116 colon-cancer grown in nude mice. The present study indicates the MR has the potential to reduce the effective dose of IRN in the clinic.


Assuntos
Liases de Carbono-Enxofre , Neoplasias do Colo , Irinotecano , Metionina , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Irinotecano/administração & dosagem , Irinotecano/farmacologia , Metionina/administração & dosagem , Humanos , Camundongos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Modelos Animais de Doenças , Células HCT116 , Linhagem Celular Tumoral , Carga Tumoral/efeitos dos fármacos
15.
Anticancer Res ; 44(4): 1499-1504, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38538002

RESUMO

BACKGROUND/AIM: Breast cancer is the most common and the deadliest cancer among women in the world. Treatment options for HER2-positive metastatic breast cancer patients are limited. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate (ADC), has recently been introduced as second-line chemotherapy for HER2-positive metastatic breast cancer. The aim of the present study was to evaluate the efficacy of methionine restriction with oral recombinant methioninase (o-rMETase) and a low-methionine diet combined with T-DXd, on a patient with HER2-positive recurrent stage IV breast cancer. CASE REPORT: A 66-year-old female was diagnosed with HER2-positive metastatic breast cancer. Computed tomography (CT) indicated peritoneal dissemination, thickening of the sigmoid colon and splenic flexure and widespread bone metastases. The patient was previously treated with fulvestrant, trastuzumab, pertuzumab, paclitaxel and capecitabine which were ineffective. T-DXd was administered as a second-line chemotherapy. Since the patient experienced strong side effects, the dose of T-Dxd was decreased. The patient began methionine restriction using o-rMETase and a low-methionine diet along with T-DXd. After the start of the combined treatment, CA15-3 and CA27.29, tumor markers for breast cancer, decreased rapidly from a very high level. The levels of both tumor markers are currently normal. Additionally, peritoneal-dissemination nodules, ascites and the thickness of the sigmoid colon and splenic flexure are no longer detected on CT. The patient maintains a high performance status, without severe side effects of the combination treatment. CONCLUSION: Methionine restriction consisting of o-rMETase and a low-methionine diet, in combination with T-DXd as second-line chemotherapy, was highly effective in a patient with HER2-positive stage IV breast cancer.


Assuntos
Neoplasias da Mama , Camptotecina/análogos & derivados , Liases de Carbono-Enxofre , Imunoconjugados , Humanos , Feminino , Idoso , Neoplasias da Mama/tratamento farmacológico , Biomarcadores Tumorais , Trastuzumab/uso terapêutico , Metionina , Racemetionina , Dieta , Receptor ErbB-2
16.
Anticancer Res ; 44(3): 921-928, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38423656

RESUMO

BACKGROUND/AIM: The aim of the present study was to determine the synergy of recombinant methioninase (rMETase) and the anti-tubulin agent eribulin on fibrosarcoma cells, in comparison to normal fibroblasts, in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells and HS27 human fibroblasts were used for in vitro experiments. Four groups were analyzed in vitro: No-treatment control; eribulin; rMETase; eribulin plus rMETase. Dual-color HT1080 cells which express red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize cytoplasmic and nuclear dynamics during treatment. RESULTS: Eribulin combined with rMETase greatly decreased the viability of HT 1080 cells. In contrast, eribulin combined with rMETase did not show synergy on Hs27 normal fibroblasts. Eribulin combined with rMETase also caused more fragmentation of the nucleus than all other treatments. CONCLUSION: The combination treatment of eribulin plus rMETase demonstrated efficacy on fibrosarcoma cells in vitro. In contrast, normal fibroblasts were resistant to this combination, indicating the potential clinical applicability of the treatment.


Assuntos
Liases de Carbono-Enxofre , Fibrossarcoma , Furanos , Cetonas , Policetídeos de Poliéter , Humanos , Liases de Carbono-Enxofre/uso terapêutico , Linhagem Celular Tumoral , Fibrossarcoma/tratamento farmacológico , Fibroblastos , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico
17.
Anticancer Res ; 44(1): 31-35, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159986

RESUMO

BACKGROUND/AIM: Irinotecan (IRN), a topoisomerase I inhibitor and pro-drug of SN-38, is first-line treatment of colon cancer as part of FOLFIRI and FOLFOXIRI combination chemotherapy. However, IRN causes dose-limiting adverse events such as neutropenia and diarrhea. Dose reductions are sometimes required, which reduce efficacy. Recombinant methioninase (rMETase) targets the fundamental basis of cancer, methionine addiction, known as the Hoffman effect, and enhances the efficacy of numerous chemotherapy drugs. The present study determined the efficacy of rMETase when administered in combination with IRN. MATERIALS AND METHODS: Cell viability was assessed by cultivating the HCT-116 human colorectal cancer cell line in 96-well plates at 1×103 cells per well in Dulbecco's modified Eagle's medium (DMEM). Subsequently, HCT-116 cells were treated with increasing concentrations of SN-38, the active form of IRN, ranging from 0.5 nM to 32 nM, and/or rMETase ranging from 0.125 to 8 U/ml. After treatment for 72 h, the half-maximal inhibitory concentration (IC50) of SN-38 alone and rMETase alone for HCT-116 cells were determined. Using the IC50 concentration of rMETase, we determined the IC50 of SN-38 in combination with rMETase. Cell viability was determined with the cell-counting Kit-8 with the WST-8 reagent.. RESULTS: The IC50 of rMETase alone for the HCT-116 cells was 0.55 U/ml, and the IC50 of IRN (SN-38) alone was 3.50 nM. rMETase at 0.55 U/ml lowered the IC50 of SN-38 to 0.232 nM (p<0.0001), a 15-fold reduction. CONCLUSION: rMETase and IRN are strongly synergistic, giving rise to the possibility of lowering the effective dose of IRN for the treatment of patients with colon cancer, thereby reducing its severe toxicity. This new strategy will allow more patients with cancer to be effectively treated with IRN.


Assuntos
Neoplasias do Colo , Humanos , Irinotecano/farmacologia , Neoplasias do Colo/tratamento farmacológico , Liases de Carbono-Enxofre , Células Tumorais Cultivadas , Proteínas Recombinantes
18.
J Clin Med ; 12(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137813

RESUMO

BACKGROUND: The objective of this study was to compare the long-term prognosis of patients with T1 and T2 colorectal cancer (CRC) according to lymph node metastasis (LNM) and to identify risk factors for LNM. METHODS: We retrospectively reviewed patients who underwent curative resection for T1 or T2 CRC at five University-affiliated hospitals between January 2012 and December 2021. The patients were divided into several groups depending on the presence of LNM or the number of risk factors. RESULTS: Of the total 765 patients, 87 (11.3%) patients had LNM. These patients had poorer recurrence-free survival (RFS) than patients without LNM (72.6% vs. 88.6%). The multivariable analysis showed that high-grade tumors (p = 0.003), lymphovascular invasion (p < 0.001), and rectal location (p = 0.049) were independent predictors of LNM. When divided into groups according to the number of the three risk factors, the risk of LNM increased from 5.4% (ultralow-risk group; no risk factor) to 60.0% (high-risk group; all three risk factors) and the 5-year RFS rate decreased from 96.3% in the ultralow-risk group to 60% in the high-risk group (p < 0.001). CONCLUSION: Radical surgery should be considered for T1 and T2 CRC patients with these risk factors.

19.
Ann Surg Treat Res ; 104(5): 274-280, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37179695

RESUMO

Purpose: This retrospective study aimed to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the time interval from symptom onset to surgery and on the operative outcomes of laparoscopic appendectomy for patients with acute appendicitis. Methods: Between October 2018 and July 2021, laparoscopic appendectomy was performed in 502 patients with acute appendicitis admitted to Hallym University Chuncheon Sacred Heart Hospital in Chuncheon, Korea. We compared demographic data, serum levels of inflammatory markers, time to event of appendicitis, and operative outcomes between the pre-COVID-19 and post-COVID-19 pandemic groups. Results: Laparoscopic appendectomy was performed in 271 patients in the pre-COVID-19 group and in 231 patients in the post-COVID-19 group. There were no differences in baseline characteristics, serum inflammatory marker levels, or the proportions of complicated appendicitis between the groups (25.1%, pre-COVID-19 vs. 31.6%, post-COVID-19; P = 0.106). The time intervals between symptom onset and hospital arrival (24.42 hours vs. 23.59 hours, P = 0.743) and between hospital arrival and the start of surgery (10.12 hours vs. 9.04 hours, P = 0.246) did not increase post-COVID-19. The overall 30-day postoperative complication rate did not differ significantly between the groups (9.6% vs. 10.8%, P = 0.650), and the severity of 30-day postoperative complications was also similar in both groups (P = 0.447). Conclusion: This study demonstrates that hospitalization and surgeries were not delayed in patients with acute appendicitis and that the operative outcomes of laparoscopic appendectomy did not worsen despite the COVID-19 pandemic.

20.
BMC Surg ; 22(1): 230, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710415

RESUMO

BACKGROUND: Perforated peptic ulcer (PPU) is a common emergency condition requiring surgery using laparoscopy or open repair of the perforated site. The aim of this study was to assess the role of laparoscopic surgery (LS) based on the safety and efficacy for PPU. METHODS: Medical records of the consecutive patients who underwent LS or open surgery (OS) for PPU at five hospitals between January 2009 and December 2019 were retrospectively reviewed. After propensity score matching, short-term perioperative outcomes were compared between LS and OS in selected patients. RESULTS: Among the 598 patients included in the analysis, OS was more frequently performed in patients with worse factors, including older age, a higher American Society of Anesthesiologists score, more alcohol use, longer symptom duration, a higher Boey score, a higher serum C-reactive protein level, a lower serum albumin level, and a larger-diameter perforated site. After propensity score matching, 183 patients were included in each group; variables were well-balanced between-groups. Postoperative complications were not different between groups (24.6% LS group vs. 31.7% OS group, p = 0.131). However, postoperative length of hospital stay (10.03 vs. 12.53 days, respectively, p = 0.003) and postoperative time to liquid intake (3.75 vs. 5.26 days, p < 0.001) were shorter in the LS group. CONCLUSIONS: LS resulted in better functional recovery than OS and can be safely performed for treatment of PPU. When performed by experienced surgeons, LS is an alternative option, even for hemodynamically unstable patients.


Assuntos
Laparoscopia , Úlcera Péptica Perfurada , Humanos , Laparoscopia/métodos , Tempo de Internação , Úlcera Péptica Perfurada/etiologia , Úlcera Péptica Perfurada/cirurgia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
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