Pub Date : 2024-09-14DOI: 10.1177/15347354241267979
Ibrahim Musa, Nan Yang, Joseph Breslin, Orion Paulden, Jan Geliebter, Raj Tiwari, Xiu-Min Li
Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.
{"title":"Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53","authors":"Ibrahim Musa, Nan Yang, Joseph Breslin, Orion Paulden, Jan Geliebter, Raj Tiwari, Xiu-Min Li","doi":"10.1177/15347354241267979","DOIUrl":"https://doi.org/10.1177/15347354241267979","url":null,"abstract":"Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective:Development of chemotherapy-induced peripheral neuropathy (CIPN) poses significant challenges in cancer treatment, often leading to dose reductions or treatment discontinuation. Goshajinkigan (GJG), a traditional Japanese medicine, has shown promise for alleviating CIPN symptoms. This multicenter, randomized controlled trial aimed to prospectively examine the efficacy of GJG in preventing paclitaxel-induced peripheral neuropathy.Methods:This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. The participants were randomized into Groups A (GJG initiation after onset of grade 2 neuropathy) and B (prophylactic administration of GJG from 1 week before chemotherapy). The primary endpoints were the proportion with a maximum sensory neuropathy grade and visual analog scale (VAS) scores. The secondary endpoints were the rate of chemotherapy completion and paclitaxel dose reduction due to neurotoxicity.Results:Prophylactic GJG administration (Group B) resulted in significant benefits. While both groups had a similar incidence of grade 2 sensory neuropathy, all patients in Group B with grade 2 neuropathy completed treatment without requiring additional analgesics. Group B exhibited lower VAS scores by the end of the study, reduced reliance on adjuvant analgesics (27.3% vs 66.7% in Group A), and significantly less frequent persistent CIPN 6 months post-chemotherapy (18.2% vs 55.6% in Group A). No differences were observed in the chemotherapy completion rates or CIPN-related changes between the groups.Conclusion:GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings.
目的：化疗诱发的周围神经病变（CIPN）是癌症治疗中的重大挑战，通常会导致剂量减少或治疗中止。Goshajinkigan（GJG）是一种传统的日本药物，在缓解 CIPN 症状方面显示出良好的前景。这项多中心随机对照试验旨在前瞻性地研究 GJG 在预防紫杉醇诱发的周围神经病变方面的疗效。参与者被随机分为A组（出现2级神经病变后开始服用GJG）和B组（化疗前1周开始预防性服用GJG）。主要终点是感觉神经病变达到最高级别的比例和视觉模拟量表（VAS）评分。次要终点是化疗完成率和因神经毒性导致的紫杉醇剂量减少。虽然两组的 2 级感觉神经病变发生率相似，但 B 组所有 2 级神经病变患者都完成了治疗，无需额外使用镇痛药。研究结束时，B 组患者的 VAS 评分较低，对辅助镇痛药的依赖性降低（27.3% 对 A 组的 66.7%），化疗后 6 个月持续性 CIPN 的发生率明显降低（18.2% 对 A 组的 55.6%）。结论：在紫杉醇化疗期间，预防性服用 GJG 有可能减轻 CIPN 症状。虽然前景看好，但要全面验证这些研究结果，还必须进一步开展安慰剂对照和客观测量研究。
{"title":"Effectiveness of the Traditional Japanese Medicine Goshajinkigan in Preventing Paclitaxel-Induced Peripheral Neuropathy: A Multicenter Randomized Comparative Trial","authors":"Yukiko Matsumura, Masayuki Futagami, Tsukasa Baba, Shu Soeda, Hidemichi Watari, Yukihiro Terada, Hideki Tokunaga, Satoru Nagase, Toru Nakanishi, Michiko Kaiho, Yoshihito Yokoyama","doi":"10.1177/15347354241278635","DOIUrl":"https://doi.org/10.1177/15347354241278635","url":null,"abstract":"Objective:Development of chemotherapy-induced peripheral neuropathy (CIPN) poses significant challenges in cancer treatment, often leading to dose reductions or treatment discontinuation. Goshajinkigan (GJG), a traditional Japanese medicine, has shown promise for alleviating CIPN symptoms. This multicenter, randomized controlled trial aimed to prospectively examine the efficacy of GJG in preventing paclitaxel-induced peripheral neuropathy.Methods:This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. The participants were randomized into Groups A (GJG initiation after onset of grade 2 neuropathy) and B (prophylactic administration of GJG from 1 week before chemotherapy). The primary endpoints were the proportion with a maximum sensory neuropathy grade and visual analog scale (VAS) scores. The secondary endpoints were the rate of chemotherapy completion and paclitaxel dose reduction due to neurotoxicity.Results:Prophylactic GJG administration (Group B) resulted in significant benefits. While both groups had a similar incidence of grade 2 sensory neuropathy, all patients in Group B with grade 2 neuropathy completed treatment without requiring additional analgesics. Group B exhibited lower VAS scores by the end of the study, reduced reliance on adjuvant analgesics (27.3% vs 66.7% in Group A), and significantly less frequent persistent CIPN 6 months post-chemotherapy (18.2% vs 55.6% in Group A). No differences were observed in the chemotherapy completion rates or CIPN-related changes between the groups.Conclusion:GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1177/15347354241254899
{"title":"Corrigendum to “Pharmacokinetic Analysis of Prognostic Factors in Patients With Advanced-Stage Intrahepatic Cholangiocarcinoma Following the Administration of Capsule Formulation of the Standardized Extract of Atractylodes lancea (Thunb) DC”","authors":"","doi":"10.1177/15347354241254899","DOIUrl":"https://doi.org/10.1177/15347354241254899","url":null,"abstract":"","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1177/15347354241239930
Lea Raiber, Christian Raff, Johanna Thiele, Klaus Kramer
Background:Integrative nursing (IN) is an essential component of integrative medicine and integrative oncology. IN includes a range of external naturopathic, integrative nursing interventions, such as compresses, embrocation, and foot/hand baths, aimed at alleviating symptoms and side effects of conventional treatment. The project IMPLEMENT-UKU (“Implementation of IN at the University Hospital Ulm”) was accompanied by a descriptive pilot study on the use of IN interventions on cancer-related symptoms in oncology inpatients, the characterization of these patients and the evaluation of the impact.Methods:A single-arm study was conducted using a paper-based questionnaire administered before the IN interventions (t0) and 24 hours after the IN interventions (t1). Topics included sociodemographic data, symptoms, quality of life, health status, psychological burden, attitudes, and experience and satisfaction with the IN interventions. Analyses were descriptive using absolute and relative frequencies.Results:During the 6-month study period out of 66 patients recommended for IN consultation by medical and nursing staff on 2 wards, 62 (93.9%) accepted the offer. Of those patients who received IN, 21 patients (33.9%) participated in the study. The number of IN interventions received per patient ranged from 1 to 3 during the 24-hour survey period. And a total of 36 IN interventions were performed: The most treated body region was the feet/legs (50.0%), followed by the back (25.0%), using oils such as solum oil (41.7%) and lavender oil (13.9%). Embrocation (77.8%) was the predominant type of IN intervention. For patients, the mean FACIT-F score was 29.2 ± 12.5. The mean PHQ-4 score was 3.0 ± 1.9. Regarding sleep quality in the last 4 weeks, 13 participants (61.9%) described it as rather or very poor. Satisfaction with the IN was high, with a large proportion of participants evaluating the IN interventions very positively.Conclusion:The study’s findings suggest that there is a great need for IN among oncology inpatients. These patients are open to and interested in IN interventions and evaluate them positively. IN provides a promising opportunity to provide non-pharmacological support to inpatients. The integration of IN in conventional oncology care settings may enhance patient-centered care and contribute to improved patient wellbeing.
背景：整合护理（IN）是整合医学和整合肿瘤学的重要组成部分。中西医结合护理包括一系列外部自然疗法和中西医结合护理干预措施，如热敷、栓塞、足浴/手浴等，旨在减轻常规治疗的症状和副作用。IMPLEMENT-UKU（"在乌尔姆大学医院实施 IN"）项目同时还开展了一项描述性试点研究，研究内容包括使用 IN 干预措施治疗肿瘤住院患者的癌症相关症状、这些患者的特征以及对其影响的评估。方法：该研究为单臂研究，在 IN 干预前（t0）和 IN 干预后（t1）24 小时内发放纸质问卷。主题包括社会人口学数据、症状、生活质量、健康状况、心理负担、态度以及对 IN 干预的体验和满意度。结果：在为期 6 个月的研究期间，2 个病房的医护人员建议 66 名患者接受 IN 咨询，其中 62 人（93.9%）接受了咨询。在接受 IN 的患者中，21 名患者（33.9%）参与了研究。在 24 小时的调查期间，每位患者接受 IN 干预的次数从 1 次到 3 次不等。总共进行了 36 次 IN 干预：接受治疗最多的身体部位是足部/腿部（50.0%），其次是背部（25.0%），使用的精油包括苏伦精油（41.7%）和薰衣草精油（13.9%）。栓塞（77.8%）是最主要的 IN 干预方式。患者的平均 FACIT-F 评分为 29.2 ± 12.5。PHQ-4平均得分为3.0 ± 1.9。关于最近 4 周的睡眠质量，13 名参与者（61.9%）认为比较差或非常差。结论：研究结果表明，肿瘤住院患者对心理治疗有很大的需求。这些患者对 IN 干预持开放态度，也很感兴趣，并给予积极评价。心理治疗为住院患者提供非药物支持提供了一个大有可为的机会。在传统的肿瘤治疗环境中融入心理治疗，可以加强以患者为中心的治疗，有助于改善患者的健康状况。
{"title":"Integrative Nursing Interventions for Cancer-Related Symptoms in Oncology Inpatients: Results of a Descriptive Pilot Study","authors":"Lea Raiber, Christian Raff, Johanna Thiele, Klaus Kramer","doi":"10.1177/15347354241239930","DOIUrl":"https://doi.org/10.1177/15347354241239930","url":null,"abstract":"Background:Integrative nursing (IN) is an essential component of integrative medicine and integrative oncology. IN includes a range of external naturopathic, integrative nursing interventions, such as compresses, embrocation, and foot/hand baths, aimed at alleviating symptoms and side effects of conventional treatment. The project IMPLEMENT-UKU (“Implementation of IN at the University Hospital Ulm”) was accompanied by a descriptive pilot study on the use of IN interventions on cancer-related symptoms in oncology inpatients, the characterization of these patients and the evaluation of the impact.Methods:A single-arm study was conducted using a paper-based questionnaire administered before the IN interventions (t0) and 24 hours after the IN interventions (t1). Topics included sociodemographic data, symptoms, quality of life, health status, psychological burden, attitudes, and experience and satisfaction with the IN interventions. Analyses were descriptive using absolute and relative frequencies.Results:During the 6-month study period out of 66 patients recommended for IN consultation by medical and nursing staff on 2 wards, 62 (93.9%) accepted the offer. Of those patients who received IN, 21 patients (33.9%) participated in the study. The number of IN interventions received per patient ranged from 1 to 3 during the 24-hour survey period. And a total of 36 IN interventions were performed: The most treated body region was the feet/legs (50.0%), followed by the back (25.0%), using oils such as solum oil (41.7%) and lavender oil (13.9%). Embrocation (77.8%) was the predominant type of IN intervention. For patients, the mean FACIT-F score was 29.2 ± 12.5. The mean PHQ-4 score was 3.0 ± 1.9. Regarding sleep quality in the last 4 weeks, 13 participants (61.9%) described it as rather or very poor. Satisfaction with the IN was high, with a large proportion of participants evaluating the IN interventions very positively.Conclusion:The study’s findings suggest that there is a great need for IN among oncology inpatients. These patients are open to and interested in IN interventions and evaluate them positively. IN provides a promising opportunity to provide non-pharmacological support to inpatients. The integration of IN in conventional oncology care settings may enhance patient-centered care and contribute to improved patient wellbeing.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140836032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1177/15347354241237972
Miriam Ortiz, Maren Luise Schröder, Benno Brinkhaus, Barbara Stöckigt
Background:Breast cancer survivors often suffer from diagnosis- and therapy-related long-term side effects, such as cancer related fatigue, restricted stress resilience and quality of life. Walking as a physical activity and mindfulness practice have been shown to be helpful in studies. The aim of this study was to compare the individual experiences and subjectively perceived effects of walking in combination with mindfulness practice with moderate walking alone in breast cancer patients. This paper focuses on the qualitative results of a mixed-methods pilot study.Methods:Breast cancer patients who had finished their primary oncologic treatment at least 6 months ago were randomized to an 8-week group intervention program of either mindful walking or moderate walking. Within the qualitative study part, semi-structured focus group interviews (2 interviews per study arm) were conducted and analyzed using a qualitative content analysis approach. Audio recorded interviews were transcribed verbatim and pseudonymized. The subsequent data analysis was performed by using MAXQDA®.Results:A total of 51 women (mean age 55.8 [SD 10.9] years) were included in the RCT, among these 20 (mean age 56.7 [SD 12.0] years) participated in the focus group interviews (n = 11 patients of the mindful walking group; n = 9 patients of the walking group). Breast cancer patients in both groups described different effects in the complex areas of self-efficacy, coping, body awareness and self-reflection. While mindful walking primarily promoted body awareness and inner strength by mindfulness in breast cancer patients, moderate walking promoted self-efficacy by a confidence of their body and an easily integrated and accepted way of physical activity.Conclusions:Study interventions and the study setting triggered processes and reflections on one’s own health and situation. However, mindful walking and moderate walking seem to address different resources. This important knowledge may help oncologists and other therapists to assess what type of interventions can best meet the needs and requirements of individual patients.Trial registration:DKRS00011521; prospectively registered 21.12.2016; https://drks.de/search/de/trial/DRKS00011521
{"title":"Implementation of a Mindful Walking Intervention in Breast Cancer Patients After Their Primary Oncologic Treatment: Results of a Qualitative Study Within a Randomized Controlled Trial","authors":"Miriam Ortiz, Maren Luise Schröder, Benno Brinkhaus, Barbara Stöckigt","doi":"10.1177/15347354241237972","DOIUrl":"https://doi.org/10.1177/15347354241237972","url":null,"abstract":"Background:Breast cancer survivors often suffer from diagnosis- and therapy-related long-term side effects, such as cancer related fatigue, restricted stress resilience and quality of life. Walking as a physical activity and mindfulness practice have been shown to be helpful in studies. The aim of this study was to compare the individual experiences and subjectively perceived effects of walking in combination with mindfulness practice with moderate walking alone in breast cancer patients. This paper focuses on the qualitative results of a mixed-methods pilot study.Methods:Breast cancer patients who had finished their primary oncologic treatment at least 6 months ago were randomized to an 8-week group intervention program of either mindful walking or moderate walking. Within the qualitative study part, semi-structured focus group interviews (2 interviews per study arm) were conducted and analyzed using a qualitative content analysis approach. Audio recorded interviews were transcribed verbatim and pseudonymized. The subsequent data analysis was performed by using MAXQDA<jats:sup>®</jats:sup>.Results:A total of 51 women (mean age 55.8 [SD 10.9] years) were included in the RCT, among these 20 (mean age 56.7 [SD 12.0] years) participated in the focus group interviews (n = 11 patients of the mindful walking group; n = 9 patients of the walking group). Breast cancer patients in both groups described different effects in the complex areas of self-efficacy, coping, body awareness and self-reflection. While mindful walking primarily promoted body awareness and inner strength by mindfulness in breast cancer patients, moderate walking promoted self-efficacy by a confidence of their body and an easily integrated and accepted way of physical activity.Conclusions:Study interventions and the study setting triggered processes and reflections on one’s own health and situation. However, mindful walking and moderate walking seem to address different resources. This important knowledge may help oncologists and other therapists to assess what type of interventions can best meet the needs and requirements of individual patients.Trial registration:DKRS00011521; prospectively registered 21.12.2016; https://drks.de/search/de/trial/DRKS00011521","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-22DOI: 10.1177/15347354241247223
Qiang Wang, Mengyuan Chen, Xiaofang Tang
Background:Luteolin, a common dietary flavonoid found in plants, has been shown to have anti-cancer properties. However, its exact mechanisms of action in non-small cell lung cancer (NSCLC) are still not fully understood, particularly its role in regulating broader genomic networks and specific gene targets. In this study, we aimed to elucidate the role of microRNAs (miRNAs) in NSCLC treated with luteolin, using A549 cells as a model system.Materials and Methods:miRNA profiling was conducted on luteolin-treated A549 cells using Exiqon microarrays, with validation of selected miRNAs by qRT-PCR. Bioinformatic analysis identified the regulatory roles of miRNAs in biological processes and pathways following luteolin treatment. Computational algorithms were employed to identify potential target genes. A549 cells were transfected with miR-106a-5p mimic and inhibitor or their corresponding controls. The expression levels of 2 genes, twist basic helix-loop-helix transcription factor 1 (TWIST1) and matrix metallopeptidase 2 (MMP2), and cell migration were assessed.Results:miRNA profiling identified 341 miRNAs, with 18 exhibiting significantly altered expression ( P < 0.05). Subsequent qRT-PCR analysis confirmed altered expression of 6 selected miRNAs. KEGG and GO analyses revealed significant alterations in pathways and biological processes crucial for tumor biology. TWIST1 and MMP2, which both contain conserved miR-106a-5p binding sites, exhibited an inverse correlation with the expression levels of miR-106a-5p. Dual-luciferase reporter assays confirmed TWIST1 and MMP2 as direct targets of miR-106a-5p. Luteolin treatment led to a reduction in A549 cell migration, and this reduction was further amplified by the overexpression of miR-106a-5p.Conclusion:Luteolin inhibits A549 cell migration by modulating the miRNA landscape, shedding light on its mechanisms and laying the foundation for miRNA-based therapeutic approaches for NSCLC.
{"title":"Luteolin Inhibits Lung Cancer Cell Migration by Negatively Regulating TWIST1 and MMP2 Through Upregulation of miR-106a-5p","authors":"Qiang Wang, Mengyuan Chen, Xiaofang Tang","doi":"10.1177/15347354241247223","DOIUrl":"https://doi.org/10.1177/15347354241247223","url":null,"abstract":"Background:Luteolin, a common dietary flavonoid found in plants, has been shown to have anti-cancer properties. However, its exact mechanisms of action in non-small cell lung cancer (NSCLC) are still not fully understood, particularly its role in regulating broader genomic networks and specific gene targets. In this study, we aimed to elucidate the role of microRNAs (miRNAs) in NSCLC treated with luteolin, using A549 cells as a model system.Materials and Methods:miRNA profiling was conducted on luteolin-treated A549 cells using Exiqon microarrays, with validation of selected miRNAs by qRT-PCR. Bioinformatic analysis identified the regulatory roles of miRNAs in biological processes and pathways following luteolin treatment. Computational algorithms were employed to identify potential target genes. A549 cells were transfected with miR-106a-5p mimic and inhibitor or their corresponding controls. The expression levels of 2 genes, twist basic helix-loop-helix transcription factor 1 (TWIST1) and matrix metallopeptidase 2 (MMP2), and cell migration were assessed.Results:miRNA profiling identified 341 miRNAs, with 18 exhibiting significantly altered expression ( P < 0.05). Subsequent qRT-PCR analysis confirmed altered expression of 6 selected miRNAs. KEGG and GO analyses revealed significant alterations in pathways and biological processes crucial for tumor biology. TWIST1 and MMP2, which both contain conserved miR-106a-5p binding sites, exhibited an inverse correlation with the expression levels of miR-106a-5p. Dual-luciferase reporter assays confirmed TWIST1 and MMP2 as direct targets of miR-106a-5p. Luteolin treatment led to a reduction in A549 cell migration, and this reduction was further amplified by the overexpression of miR-106a-5p.Conclusion:Luteolin inhibits A549 cell migration by modulating the miRNA landscape, shedding light on its mechanisms and laying the foundation for miRNA-based therapeutic approaches for NSCLC.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140636952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1β, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1β mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1β, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1β after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.
{"title":"Jiedu Xiaozheng Yin Inhibits the Progression of Colitis Associated Colorectal Cancer by Stimulating Macrophage Polarization Towards an M1 Phenotype via the TLR4 Pathway","authors":"Haiqin Liu, Shuo Yan, Ruiming Yang, Caidi Huang, Kangyue Guo, Shi Wang, Yunmei Huang, Dongyi Shen, Ying Lin, Zhiyun Cao, Hangyan Zhong, Jiumao Lin, Xuzheng Chen","doi":"10.1177/15347354241247061","DOIUrl":"https://doi.org/10.1177/15347354241247061","url":null,"abstract":"To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1β, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1β mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1β, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1β after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction:Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study.Results:The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group ( P < .05).Conclusion:Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients’ quality of life.
{"title":"The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial","authors":"Zahra Keshtpour Amlashi, Fatemeh Sheida, Robab Anbiaee, Leili Tapak, Seyed Rohallah Hosseini, Hossein Mosaedian, Nastaran Barati","doi":"10.1177/15347354241237520","DOIUrl":"https://doi.org/10.1177/15347354241237520","url":null,"abstract":"Introduction:Although breast cancer is common worldwide, if diagnosed early and treated on time, the probability of recovery is high and patients often experience a long life. Reducing the quality of life is a common side effect in patients. Melatonin may have an important role in fatigue, sleep disorders and, as a result, the health-related quality of life (HRQoL) in people. About 184 patients with breast cancer were enrolled in 2 groups: intervention with daily melatonin intake of 18 mg for 3 years (93 patients) and the control group with placebo intake (91 patients). Health-related quality of life and the effect of melatonin on increasing that were evaluated with the EORTC QLQ-C30 questionnaire, third edition at the beginning, 2 months later and 3 years after the beginning of the study.Results:The general score of the HRQoL was significantly different both in the passage of time and in the comparative study of the 2 groups, and it was better in the melatonin group ( P < .05).Conclusion:Long-term use of 18 mg of melatonin for 3 years in patients with non-metastatic breast cancer can lead to an increase in the patients’ quality of life.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140611515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-09DOI: 10.1177/15347354241242120
Ying-Wen Su, Wen-Yu Huang, Sheng-Hsiang Lin, Po-Sheng Yang
Objectives:To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC).Methods:Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models.Results:Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (β ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model).Conclusions:Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.
{"title":"Effects of Reishimmune-S, a Fungal Immunomodulatory Peptide Supplement, on the Quality of Life and Circulating Natural Killer Cell Profiles of Patients With Early Breast Cancer Receiving Adjuvant Endocrine Therapy","authors":"Ying-Wen Su, Wen-Yu Huang, Sheng-Hsiang Lin, Po-Sheng Yang","doi":"10.1177/15347354241242120","DOIUrl":"https://doi.org/10.1177/15347354241242120","url":null,"abstract":"Objectives:To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC).Methods:Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models.Results:Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19<jats:sup>+</jats:sup> lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A<jats:sup>+</jats:sup> and NKp30<jats:sup>+</jats:sup> NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30<jats:sup>+</jats:sup> NK cells (β ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model).Conclusions:Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background:Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID.Method:This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis.Result:The RR of high-grade diarrhea and all-grade diarrhea were 0.31 ( I2 = 51%, 95% CI: 0.14-0.69; P = .004) and .76 ( I2 = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I2 = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I2 = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I2 = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks.Conclusion:This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.
{"title":"Efficiency of Protective Interventions on Irinotecan-Induced Diarrhea: A Systematic Review and Meta-Analysis","authors":"Yanxi He, Lili Wu, Xiaoyi Qi, Xuan Wang, Bing He, Wei Zhang, Wenjing Zhao, Mingming Deng, Xia Xiong, Yu Wang, Sicheng Liang","doi":"10.1177/15347354241242110","DOIUrl":"https://doi.org/10.1177/15347354241242110","url":null,"abstract":"Background:Irinotecan is widely used in the treatment of various solid tumors, but the adverse effects from it, especially diarrhea, limit its use. Several clinical trials of prophylactic treatment of irinotecan-induced diarrhea (IID) have been ongoing, and some of the data are controversial. This encouraged us to conduct a meta-analysis of the effects of interventions on preventing IID.Method:This systematic review was conducted based on the PRISMA statement. We performed literature searches from PubMed, Web of Science, Embase, and Cochrane Library. The number registered in PROSPERO is CRD42022368633. After searching 1034 articles in the database and references, 8 studies were included in this meta-analysis.Result:The RR of high-grade diarrhea and all-grade diarrhea were 0.31 ( I<jats:sup>2</jats:sup> = 51%, 95% CI: 0.14-0.69; P = .004) and .76 ( I<jats:sup>2</jats:sup> = 65%, 95% CI: 0.62-0.93; P < .008) respectively, thus the use of intervention measures for preventing IID is effective, and the risk reduction of high-grade diarrhea was more significant. Subgroup analysis revealed that the monotherapy group (RR: 0.48, 95% CI: 0.21-1.13, I<jats:sup>2</jats:sup> = 0%) and combination therapy group (RR: 0.14, 95% CI: 0.06-0.32, I<jats:sup>2</jats:sup> = 0%) in the risk of high-grade diarrhea had no significant heterogeneity within the groups, and traditional herbal medicines (Kampo medicine Hangeshashin-to, PHY906 and hot ironing with Moxa Salt Packet on Tianshu and Shangjuxu) were effective preventive measures (RR:0.20, 95% CI: 0.07-0.60, I<jats:sup>2</jats:sup> = 0%). The Jadad scores for traditional herbal medicines studies were 3, and the follow-up duration was only 2 to 6 weeks.Conclusion:This systematic review and meta-analysis suggest that preventive treatments significantly reduced the risk of high-grade and all-grade diarrhea, confirming the efficacy in the incidence and severity of IID, among which traditional herbal medicines (baicalin-containing) provided a protective effect in reducing the severity of IID. However, the traditional herbal medicines studies were of low quality. Combined irinotecan therapy can obtain better preventive effects than monotherapy of IID. These would be helpful for the prevention of IID in clinical practice.","PeriodicalId":13734,"journal":{"name":"Integrative Cancer Therapies","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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