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Cancer metastasis is responsible for the majority of cancer-related deaths. Accordingly, to reduce metastasis remains a vital challenge in clinical practice, and phytochemicals have taken an attention as anti-metastatic agents. Apigenin, a plant flavone, showed anti-cancer effects against in various animal models, moreover its potentials inhibiting tumor metastasis have been reported. Herein, we analyzed the overall features at what apigenin inhibited metastasis and its action modes. We searched for articles in MEDLINE (Pubmed), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) through March 2023. Total 6 animal studies presented anti-metastatic effects of apigenin using 5 difference experimental models, while the mechanisms involved modulations of epithelial-mesenchymal transition (EMT), matrix metalloproteinases (MMPs), angiogenesis, and various metastasis-related signaling pathways. This review provides an overall potential of apigenin as a candidate reducing the risk of cancer metastasis.
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Introduction: Terminal-stage hepatocellular carcinoma (HCC) is inoperable and currently has no form of adjuvant therapy. This study examined the anticancer herbal extract Gun-Chil-Jung (GCJ) combined with cytokine-induced killer (CIK)-cell-based immunotherapy as a palliative therapy for terminal HCC. We report the case of an HCC patient with extended overall survival and improved symptoms and tumor marker levels following combination therapy with GCJ and CIK cell-based immunotherapy. Baseline Characteristics: From March to July 2020, a 57-year-old man who had been diagnosed with HCC underwent combination treatment with GCJ and CIK cell-based immunotherapy. By August 2021, he was prescribed GCJ. After treatment, the patient's condition was evaluated with respect to overall survival, tumor markers, symptoms, abdominal computed tomography findings, chest x-ray results, and Eastern Cooperative Oncology Group (ECOG) grade. Results: The patient's overall survival, tumor marker levels, ECOG grade, and symptoms, including ascites, lower limb edema, jaundice, pleural effusion, and fatigue, were largely alleviated. Conclusion: We expect that this combination therapy may be an option for palliative therapy of terminal HCC.
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Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.
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Linfócitos T CD8-Positivos , Neoplasias , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Receptor de Morte Celular Programada 1RESUMO
Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of Panax ginseng C.A. Meyer, inhibits tumor growth and has the potential to prevent tumor metastasis. Herein, we systematically reviewed the anti-metastatic effects of Rg3 from experimental studies. We searched for articles in three research databases, MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 2022. In total, 14 studies (eight animal and six in vitro) provide data on the anti-metastatic effects of Rg3 and the relevant mechanisms. The major anti-metastatic mechanisms of Rg3 involve cancer stemness, epithelial mesenchymal transition (EMT) behavior, and angiogenesis. Taken together, Rg3 would be one of the herbal resources in anti-metastatic drug developments through further well-designed investigations and clinical studies. Our review provides valuable reference data for Rg3-derived studies targeting tumor metastasis.
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Ginsenosídeos , Neoplasias Pulmonares , Panax , Animais , Transição Epitelial-Mesenquimal , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Neoplasias Pulmonares/patologiaRESUMO
Integrative oncology is being increasingly adopted in mainstream cancer care to strengthen anticancer effects and to control cancer-related symptoms.The objective of this study is to identify the characteristics of patients with lung cancer treated at an integrative cancer center in Korea and to determine the effects of integrative cancer treatment (ICT) on survival outcome in traditional Korean medicine (TKM).We reviewed medical records for lung cancer patients who visited a single integrative clinical setting, East-West Cancer Center, between January 2014 and December 2015. We classified the patients into groups according to their ICT and whether or not they underwent anticancer traditional Korean Medicine treatment with a multiherbal formula containing Panax notoginseng Radix, Cordyceps militaris, P ginseng C.A.Mey., and Boswellia carterii BIRDWOOD (HangAmDan-B), with a herbal formula containing Rhus verniciflua Stoke, or with cultivated wild ginseng pharmacopuncture. A descriptive analysis of the characteristics and a survival analysis using the Kaplan-Meier curves with log rank test and a Cox proportional hazard model were performed.A total of 91 patients were included, and the majority had advanced-stage cancer. Of those patients, 45.1% were in the mono-TKM group and 39.6% were integrative group. Patients with advanced stage had significantly higher mortality than patients with early stage (crude hazard ratio [HR]: 4.41, 95% confidence interval [CI]: 1.56-12.5; adjusted HR: 6.31, 95% CI: 1.24-32.1). In the unadjusted model, for patients in the integrative group, the mortality rate was reduced by 50% compared to mono-TKM group with statistical significance. After adjusting confounders, the mortality rate of integrative group was reduced by 6% compared to mono-TKM group, suggesting positive effect on survival probability of integrative group.The results suggest that integration of TKM and conventional cancer treatment may have survival benefits in patients with lung cancer. Even though this study has limitations including heterogeneity between treatment groups, the study results suggest that ICT has positive effect on survival probability. To clarify the impacts of ICT for lung cancer and other cancers on survival outcome, further prospective study with a rigorous study design is required in multiclinical setting.
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Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Idoso , Terapias Complementares , Progressão da Doença , Feminino , Seguimentos , Humanos , Medicina Integrativa , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
[This corrects the article DOI: 10.1155/2017/8780325.].
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The present study investigated the toxicity of HangAmDan-B1 (HAD-B1) on A549-Cisplatin resistant (A549CR) cells. HADB1 inhibited the growth of A549CR cells in a concentrationdependent manner; HADB1 was more effective at inhibiting A549CR cell viability compared with vehicletreated cells. The reduction in viability may be due to Sphase cell cycle arrest and the induction of apoptosis in HADB1treated cells. Cell cycle protein profile analysis of HADB1treated A549CR cells using an InnoPharmaScreen (IPS) ProteoChipbased antibody microarray chip indicated downregulation of signal transducer and activator of transcription 3. The activities of caspase3, 8 and 9 were significantly increased in HADB1treated cells when compared with the vehicletreated control group. Furthermore, the HADB1treated group exhibited similarly increased caspase levels when compared with the Afatinibtreated group. Taken together, these observations suggest that HADB1 may be a promising candidate for further research into the therapeutic management of cisplatin-resistant lung cancer.
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Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Cisplatino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Relação Dose-Resposta a Droga , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT). METHODS: Forty-two electronic charts of patients with gastric, breast, and pancreatic cancer treated with WBCT from February 1, 2015 to September 30, 2015, were reviewed retrospectively. These charts were statistically analyzed, looking for alterations of and correlation for NKA and the expressions of systemic inflammatory markers. RESULTS: Patients with a NKA of under 300 pg/mL at admission showed significantly higher erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio (NLR) values and decreasing NLR values due to WBCT than patients with an NKA greater than 300 pg/mL. As a result of the correlation analysis between NKA and the levels of the systemic inflammatory markers, NKA showed significant negative correlation with NLR, ESR, and fibrinogen values. CONCLUSIONS: Negative correlation was identified between NKA and NLR, NKA and ESR, and NKA and fibrinogen in patients with heterogeneous cancer patients.
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Biomarcadores/metabolismo , Inflamação/imunologia , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Feminino , Humanos , Inflamação/metabolismo , Células Matadoras Naturais/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estudos RetrospectivosRESUMO
Re-education of tumor-associated macrophages (TAMs) toward antitumor effectors may be a promising therapeutic strategy for the successful treatment of cancer. HangAmDan-B (HAD-B), a herbal formula, has been used for stimulating immune function and activation of vital energy to cancer patients in traditional Korean Medicine. Previous studies have reported the anti-angiogenic and anti-metastatic effects of HAD-B; however, evidence on the immunomodulatory action of HAD-B was not demonstrated. In the present study, immunocompetent mice were used to demonstrate the suppression of the in vivo growth of allograft Lewis lung carcinoma (LLC) cells, by HAD-B. In addition, HAD-B inhibited the in vitro growth of LLC cells by driving macrophages toward M1 polarization, but not through direct inhibition of tumor cell growth. Furthermore, culture media transfer of HAD-B-treated macrophages induced apoptosis of LLC cells. Results of the present study suggest that the antitumor effect of HAD-B may be explained by stimulating the antitumor function of macrophages. Considering the importance of re-educating TAMs in the regulation of the tumor microenvironment, the present study may confer another option for anti-cancer therapeutic strategy, using herbal medicines such as HAD-B.
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Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagy-related genes affected by MRGX. Administration of MRGX at 100 µg/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 µg/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 µg/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.
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Autofagia/genética , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Células A549 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Autofagia/efeitos dos fármacos , Proteína Beclina-1/genética , Proteínas de Ciclo Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Associadas aos Microtúbulos/genética , Panax/química , Fosfoproteínas/genética , Extratos Vegetais/química , Saponinas/genética , Saponinas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
Traditional oriental herbal medicine (HM) is used by cancer patients to improve immunity. Natural killer (NK) cells are associated with development and progression of tumor and survival of cancer patients. This literature review examined randomized controlled trials (RCTs) in four electronic databases until October 2015 to evaluate the effects of oral HM on NK cells in cancer patients. Data were pooled and computed in a meta-analysis. The methodological quality was assessed according to the Cochrane risk of bias tool. Sixteen RCTs involving 1326 cancer patients were identified. Combination of HM and conventional treatment was associated with significantly higher level of NK cells compared with conventional cancer treatments (standardized mean difference, 1.218; 95% confidence interval 0.719-1.717; p < 0.001). Eight RCTs reported statistically significant improvements in the proportions or activity of NK cells in patient groups who received both HM and conventional treatment compared with patients who received conventional treatment alone, while eight RCTs reported no statistically significant differences between the two groups. Studies (n = 16) included in this review had insufficient quality of evidence with unclear (n = 1) and high (n = 15) values of the risk of bias. Although traditional oriental HM may have the positive effects on preserving the level of NK cells in cancer patients receiving conventional treatments, current evidence is inconclusive because of lack of high-quality evidence. Copyright © 2017 John Wiley & Sons, Ltd.
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Imunoterapia/métodos , Células Matadoras Naturais/metabolismo , Medicina Tradicional do Leste Asiático/métodos , Neoplasias/tratamento farmacológico , Humanos , Resultado do TratamentoRESUMO
OBJECTIVE: The aim of this study was to determine the feasibility, acceptability, and safety of using moxibustion for treating anorexia and improving quality of life in patients with metastatic cancer. METHODS: We conducted a randomized sham-controlled trial of moxibustion. Sixteen patients with metastatic cancer were recruited from Daejeon, South Korea. The patients were randomly placed into a true or a sham moxibustion group and received 10 true or sham moxibustion treatments administered to the abdomen (CV12, CV8, CV4) and legs (ST36) over a 2-week period. Outcome measures included interest in participating in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria, and compliance with the treatment plan (ie, attendance at treatment sessions). Clinical outcomes included results of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), answers on the European Organization for Research and Treatment of Cancer 30-item core quality of life (EORTC QLQ-C30) questionnaires, scores on the visual analogue scale (VAS), and the results from blood tests and a safety evaluation. RESULTS: Moxibustion was an acceptable intervention in patients with metastatic cancer. Compliance with the treatment protocol was high, with 11 patients completing all 10 treatments. No serious adverse events related to moxibustion occurred, but 4 patients in the true moxibustion group reported mild rubefaction, which disappeared in a few hours. CONCLUSION: This study suggests that moxibustion may be safely used to treat anorexia and improve quality of life in patients with metastatic cancer. However, further research is needed to confirm this result.
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Anorexia/etiologia , Anorexia/terapia , Moxibustão/efeitos adversos , Neoplasias/complicações , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Qualidade de Vida , República da CoreiaRESUMO
Background: Anorexia occurs in about half of cancer patients and is associated with high mortality rate. However, safe and long-term use of anorexia treatment is still an unmet need. Objective: The purpose of the present study was to examine the feasibility of Sipjeondaebo-tang (Juzen-taiho-to, Shi-Quan-Da-Bu-Tang) for cancer-related anorexia. Methods: A total of 32 participants with cancer anorexia were randomized to either Sipjeondaebo-tang group or placebo group. Participants were given 3 g of Sipjeondaebo-tang or placebo 3 times a day for 4 weeks. The primary outcome was a change in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes included Visual Analogue Scale (VAS) of anorexia, FAACT scale, and laboratory tests. Results: Anorexia and quality of life measured by FAACT and VAS were improved after 4 weeks of Sipjeondaebo-tang treatment. However, there was no significant difference between changes of Sipjeondaebo-tang group and placebo group. Conclusions: In the present study, [corrected] Sipjeondaebo-tang did not show a significant effect on anorexia [corrected]in patients with cancer. Further large-scale studies which compensate for the limitations of this study are needed to assess [corrected] the efficacy. Trial Registration: This trial is registered with ClinicalTrials.gov NCT02468141.
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Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.
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Alérgenos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Extratos Vegetais/farmacologia , Rhus/química , Caspases/metabolismo , Feminino , Humanos , Proteínas I-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , NF-kappa B/fisiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Fosforilação/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/isolamento & purificação , Receptores do Fator de Necrose Tumoral/metabolismo , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/antagonistas & inibidoresRESUMO
OBJECTIVES: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. METHODS: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. RESULTS: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. CONCLUSION: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.
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Evidence suggests that Rhus verniciflua Stokes (RVS) or its extract has the potential to be used for the treatment of inflammatory and neoplastic diseases. However, direct use of RVS or its extract as a herbal medicine has been limited due to the presence of urushiol, an allergenic toxin. In the present study, we prepared an extract of the allergenremoved RVS (aRVS) based on a traditional method and investigated its inhibitory effect on the growth of various types of human cancer cells, including lung (A549), breast (MCF-7) and prostate (DU-145) cancer cell lines. Notably, among the cell lines tested, treatment with the aRVS extract strongly inhibited proliferation of the A549 cells at a 0.5 mg/ml concentration for 24 h that was not cytotoxic to normal human dermal fibroblasts. Furthermore, aRVS extract treatment largely reduced the survival and induced apoptosis of the A549 cells. At the mechanistic levels, treatment with the aRVS extract led to the downregulation of Bcl-2 and Mcl-1 proteins, the activation of caspase-9/-3 proteins, an increase in cytosolic cytochrome c levels, the upregulation of Bax protein, an increase in phosphorylated p53 protein but a decrease in phosphorylated S6 protein in the A549 cells. Importantly, treatment with z-VADfmk, a pan-caspase inhibitor attenuated aRVS extract-induced apoptosis in the A549 cells. These results demonstrate firstly that aRVS extract has growth inhibitory and apoptosis-inducing effects on A549 human lung cancer cells through modulation of the expression levels and/or activities of caspases, Bcl-2, Mcl-1, Bax, p53 and S6.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Células A549 , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Células MCF-7 , Masculino , Proteína de Sequência 1 de Leucemia de Células Mieloides/biossíntese , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Extratos Vegetais/química , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Rhus/química , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/genéticaRESUMO
Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.
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Apoptose/efeitos dos fármacos , Integrina alfa5beta1/metabolismo , Neoplasias Pulmonares/fisiopatologia , Panax/química , Extratos Vegetais/farmacologia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caspase 8/genética , Caspase 8/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Humanos , Integrina alfa5beta1/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/genéticaRESUMO
Objective To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non-small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively (P = .189). The median OS rates of patients who received WBCT for >14 days but <28 days and those who received WBCT for ≥28 days were 16.2 (95% CI = 13.3-19.2) and 45.2 (95% CI = 14.4-76.0) months, respectively (P = .437). The median OS rates of patients who had undergone prior conventional treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively (P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively (P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS <3 could not be calculated. However, the mean OS rates of patients with ECOG PS <3 and with ECOG PS ≥3 were 85.7 (95% CI = 58.4-113.0) and 12.7 (95% CI = 8.5-16.9) months, respectively (P = .000). No severe adverse events were encountered. Conclusions Our study indicates that WBCT might be effective to prolong the length of survival for patients with advanced NSCLC who have previously undergone conventional treatment and have an ECOG PS <3.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Taxa de SobrevidaRESUMO
OBJECTIVES: Correlations of the levels of the nonspecific inflammatory markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and of the coagulation marker fibrinogen with the treatment period of wheel balanced cancer therapy were determined. METHODS: Electronic charts of stage IV cancer patients hospitalized from February 1, 2008, to November 30, 2013, were reviewed retrospectively. Patients whose laboratory follow-up tests included at least two data points for at least one marker were included. Patients receiving chemotherapy or radiotherapy or having Eastern Cooperative Oncology Group (ECOG) levels exceeding 2 were excluded. Correlations of the markers with the length of treatment for treatment periods ≥ 21 and ≤ 20 days were determined by gender and whether or not surgery had been performed. RESULTS: Analyses of the CRP and the ESR revealed a higher proportion of patients with stable marker levels than with increased or decreased levels. Also, only the ESR in female and the CRP in male groups had higher proportions of patients with stable marker levels than with increased or decreased levels. The ≥ 21 day group had a higher proportion of patients with stable CRP and ESR levels than the ≤ 20 day group. Only the ESR in female and the CRP in male groups had higher proportions of patients with stable marker levels in the ≥ 21 day than in the ≤ 20 day group. In addition, only the CRP in the surgery group and the ESR in the non-surgery group had higher proportions of patients with stable marker levels in the ≥ 21 day group than in the ≤ 20 day group. CONCLUSION: For stage IV cancer patients at hospitals that offer Korean medicine, more than 21 days of long-term wheel balanced cancer therapy (WBCT) should help maintain the CRP and the ESR levels and should have a favorable effect on the survival rate.
RESUMO
The purpose of this study was to observe the effects of autonomic nerve pharmacopuncture (ANP) treatment on cancer-related fatigue (CRF) in patients with advanced cancer. This observational case study was conducted at the East West Cancer Center of Daejeon University's Dunsan Korean Medical Hospital. Two patients were observed. One patient was diagnosed with left thymic cancer metastatic to the left pleura. The other patient had terminal-stage cervical cancer with iliac bone and lumbar 5 metastases. We injected mountain ginseng pharmacopuncture (MGP) into acupoints alongside the spine (Hua-Tuo-Jia-Ji-Xue, EX B2). We examined the patients for CRF using the Korean version of the Revised Piper Fatigue Scale (RPFS-K), which is a self-assessment tool. The scores on the RPFS-K for both patients tended to decrease during the treatment. Laboratory findings, including hematological changes, were also checked. Liver and renal function tests showed that the treatment was safe. Although further large-population studies are necessary, this case study suggests that ANP has a favorable effect on CRF in patients with advanced cancer.