Integrative Cancer Therapies最新文献

Background: Chemoresistance represented one of the challenges in the treatment of advanced gastric cancer (GC). Curcumol (CUR) was found to have a certain sensitizing effect on chemoresistance, although the mechanism was not yet fully understood. Purpose: To clarify the ability of CUR to intervene in the sensitivity of GC cells to Cisplatin (CDDP) by regulating the induction of ferroptosis through the P62/KEAP1/NRF2 pathway. Methods: An in vitro resistant cell line was established and treated with CUR for intervention. The synergy was evaluated using synergyfinder3.0 software. The impact of the combined use of CUR and CDDP on the proliferation, migration, and invasion of resistant GC cells was determined. The effect of CUR on ferroptosis in resistant GC cell lines was evaluated by measuring changes in reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, iron ion levels, and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Western blotting was used to verify the expression changes of the ferroptosis-related indicator GPX4 and the differential expression of the antioxidant-related pathway P62/KEAP1/NRF2, validating the mechanism by which CUR induces ferroptosis in resistant GC cells. In vivo validation was performed using a xenograft mouse model. Results: The evaluation by synergy3.0 revealed a synergistic effect between CUR and CDDP. After treatment with CUR and CDDP, resistant GC cell lines exhibited reduced proliferation, migration, and invasion capabilities. Furthermore, the resistant GC cell lines underwent ferroptosis, with significant changes observed in ferroptosis-related indicators such as ROS, MDA, iron ions, and GSH/GSSG. The ferroptosis-related targets Glutathione Peroxidase 4 (GPX4) and the antioxidant pathway P62/KEAP1/NRF2 signaling pathway also showed significant changes. In in vivo validation, the combination of CUR and CDDP inhibited the growth of subcutaneous tumors and was found to be associated with the inhibition of subcutaneous xenografts and the GPX4 and P62/KEAP1/NRF2 signaling pathways. Conclusion: This study first revealed that CUR enhanced the sensitivity of cisplatin-resistant GC cells to CDDP by inducing ferroptosis. The combination of CUR and CDDP induces ferroptosis in cisplatin-resistant GC through the P62/KEAP1/NRF2 pathway.

Objective: The Chinese medicine Jianpi-Huayu decoction (, JPHY) can alleviate cancer-related fatigue in patients with liver cancer. However, its mechanism remains unclear. In this study, we used BALB/c mice with liver cancer model to investigate whether JPHY alleviates cancer-related fatigue by regulating Th1/Th2 immune balance; and the possible association with the IL-27/STAT1 signaling pathway. Methods: We established a mouse model of liver cancer fatigue. Mice were gavaged with physiological saline, low, medium, or high concentrations of JPHY respectively; and intraperitoneal injection of fludarabine (STAT1 pathway inhibitor) with JPHY for 21 days. We recorded the general condition of the mice, and assessed fatigue using scoring criteria and Exhausted Swimming Test. We calculated the spleen and thymus indices, performed H&E staining and immunohistochemical analysis on liver tumor tissues to observe the tumor proliferation marker ki67. We quantified the secretion levels of IFN-γ and IL-2 produced by Th1 cells in serum and splenic lymphocytes, as well as the secretion of IL-4, IL-10 by Th2 cells, and IL-27 in the signaling pathway through ELISA analysis. We evaluated the expression levels of p-STAT1 and STAT1 in spleen tissues using Western blot analysis. Results: JPHY exhibits a therapeutic effect on hepatocellular carcinoma-induced splenomegaly in murine models by upregulating the pro-inflammatory cytokines IFN-γ and IL-2 and downregulating the anti-inflammatory cytokines IL-4 and IL-10. Moreover, JPHY suppresses ki67 expression, reduces tumor-related inflammation infiltration, and ameliorates cancer-associated fatigue. Additionally, the expression of phosphorylated protein p-STAT1 is down-regulated. Conclusion: JPHY may improve the Th1/Th2 immune balance through its anti-inflammatory effects and promotion of IL-27-induced STAT1 phosphorylation, thereby alleviating fatigue in mice with liver cancer.

Chemotherapy-induced leukopenia is a common side effect of cytotoxic anticancer drugs. It can deprive patients of treatment opportunities, resulting in the delay, reduction, or discontinuation of chemotherapy or other anticancer drug administration. Two researchers searched English, Chinese, Japanese, and Korean electronic databases, without limiting the time period and language, using search terms such as "Bojungikgi," "WBC," "leuko," and "neutrop." Among the human randomized controlled studies in which Bojungikgi-tang was administered to patients who underwent chemotherapy, studies reporting leukopenia-related outcomes were selected, and data extraction, bias risk assessment, and meta-analysis were performed on the selected papers. Ten studies were selected, and a systematic review with meta-analysis was conducted. Nine papers were published in China and the total number of participants was 715. As a result of administering Bojungikgi-tang to these patients, the number of patients with chemotherapy-induced leukopenia significantly decreased (OR: 0.41, 95% CI: 0.27-0.61, P = .0001, I² = 35%). Further, white blood cell counts were compared with that of the control group, and it showed an effect on prevention (MD: 0.64, 95% CI: 0.46-0.83, P < .00001, I² = 90%). A pronounced effect was observed, especially when administered after a diagnosis based on the pattern identification, such as Qi deficiency. (OR: 0.32, 95% CI: 0.18-0.58, P = .0002, I² = 0%). However, all studies had a high risk of bias due to non-blinding, and most studies had a high or uncertain risk of bias in creating random assignment orders and concealing them. Bojungikgi-tang has an effect on the prevention and treatment of chemotherapy-induced leukopenia. The effect rate can be increased when administered after proper diagnosis, and the possibility of adverse reactions and side effects is lower than that of Granulocyte-Colony Stimulating Factor (G-CSF) injection. Bojungikgi-tang appears to be useful in the treatment and prevention of leukopenia caused by cytotoxic anticancer drugs. However, it is necessary to conduct high-quality clinical studies in the future, considering the possibility of local and language bias, heterogeneity of carcinoma and intervention, and the risk of bias.Registration: PROSPERO CRD4202341054.

Background: Women with gynecological cancer often experience psychological distress, particularly in response to surgical procedures. The impact of mandala art therapy (MAT) during the perioperative period for gynecological cancer patients remains uncertain. We aimed to examine the effects of the MAT program in women with gynecological cancer.

Methods: Employing a quasi-experimental design, we recruited 126 gynecological cancer patients from a university hospital through convenience sampling. Participants were assigned to either receive the MAT program or standard perioperative care. The interventions comprised a three-session MAT program guided by a team of trained mandala psychologists. Generalized estimating equations (GEE) were employed to analyze the effects of MAT over time.

Results: A total of 126 patients were enrolled, and 118 completed the entire study. Over 90% of participants completed the perioperative MAT interventions, reporting relatively high satisfaction with the program (7.70 out of 10). Individuals in the MAT group exhibited improved therapeutic effects on STAI-S, VASS, and vital signs over time. Notably, significant group*time interaction effects were noted in STAI-S scores at both the first evaluation, T1 (β = -4.220, P < .005) and the third evaluation, T3 (β = -3.797, P < .05), and VASS scores at T1 (β = -11.186, P < .005), T2 (β = -9.915, P < .05) and T3 (β = -9.831, P < .05). Regarding vital signs, the multivariate GEE model revealed significant interaction effects in systolic blood pressure values at both T1 (β = -7.102, P < .05) and T3 (β = -10.051, P < .005), diastolic blood pressure values at T3 (β = -6.441, P < .005), and pulse values at T1 (β = -6.085, P < .005). No significant differences were observed between groups for pain, hope, or self-acceptance.

Conclusion: This study posited that MAT could serve as a valuable complementary approach in perioperative care for addressing the psychological needs of women with gynecological cancer. Subsequent research employing more robust methodologies and larger, more diverse participant samples will be necessary to validate these conclusions.

Concurrent chemoradiotherapy (CCRT) represents the established therapeutic modality for managing locally advanced non-small cell lung cancer (LA-NSCLC). However, its impact on improving the poor prognosis of LA-NSCLC patients is limited, and it can cause severe side effects. A 62-year-old Chinese female was diagnosed with unresectable stage IIIA lung adenocarcinoma. She refused CCRT. Enhanced computed tomography of the chest revealed a space-occupying lesion in her left pulmonary hilum, invading and encircling the pulmonary artery trunk. Due to the reported anti-tumor effects of basil, a stasis-removing Chinese herb, the patient received basil combined with cisplatin plus pemetrexed (CP) chemotherapy as first-line treatment. After 6 cycles of treatment, her condition achieved complete remission, and circulating tumor cells were reduced to zero. Regular follow-ups showed that the patient maintained progression-free survival for nearly 3 years. This case highlights the potential efficacy of basil combined with CP chemotherapy in treating LA-NSCLC. However, the curative effect of this regimen needs further validation through larger clinical trials.

Gastrointestinal (GI) cancer stands as one of the most prevalent forms of cancer globally, presenting a substantial medical and economic burden on cancer treatment. Despite advancements in therapies, it continues to exhibit the second highest mortality rate, primarily attributed to drug resistance and post-treatment side effects. There is an urgent need for novel therapeutic approaches to tackle this persistent challenge. Scutellaria baicalensis, widely used in Traditional Chinese Medicine (TCM), holds a profound pharmaceutical legacy. Modern pharmacological studies have unveiled its anticancer, antioxidant, and immune-enhancing properties. S. baicalensis contains hundreds of active ingredients, with flavonoids, polysaccharides, phenylethanoid glycosides, terpenoids, and sterols being the principal components. These constituents contribute to the treatment of GI cancer by inducing apoptosis in tumor cells, arresting the cell cycle, inhibiting tumor proliferation and metastasis, regulating the tumor microenvironment, modulating epigenetics, and reversing drug resistance. Furthermore, the utilization of modern drug delivery technologies can enhance the bioavailability and therapeutic efficacy of TCM. The treatment of GI cancer with S. baicalensis is characterized by its multi-component, multi-target, and multi-pathway advantages, and S. baicalensis has a broad prospect of becoming a clinical adjuvant or even the main therapy for GI cancer.

Background: A statistical model is essential in determining the appropriate predictive indicators for therapies in many types of cancers. Predictors have been compared favorably to the traditional systems for many cancers. Thus, this study has been proposed as a new standard approach. A recent study on the clinical efficacy of Atractylodes lancea (Thunb) DC. (AL) revealed the higher clinical benefits in patients with advanced-stage intrahepatic cholangiocarcinoma (ICC) treated with AL compared with standard supportive care. We investigated the relationships between clinical efficacy and pharmacokinetic parameters of serum bioactivity of AL and its active constituent atractylodin and determined therapeutic ranges.

Methods: Group 1 of advanced-stage ICC patients received daily doses of 1000 mg of standardized extract of the capsule formulation of AL (CMC-AL) for 90 days. Group 2 received daily doses of 1000 mg of CMC-AL for 14 days, followed by 1500 mg for 14 days, and 2000 mg for 62 days. Group 3 (control group) received palliative care. Cox proportional hazard model and Receiver Operating Characteristic (ROC) were applied to determine the cut-off values of AUC_0-inf, C_max, and C_avg associated with therapeutic outcomes. Number needed to treat (NNT) and relative risk (RR) were also applied to determine potential predictors.

Results: The AUC_0-inf of total AL bioactivity of >96.71 µg hour/ml was identified as a promising predictor of disease prognosis, that is, progression-free survival (PFS) and disease control rate (DCR). C_max of total AL bioactivity of >21.42 was identified as a predictor of the prognosis of survival. The therapeutic range of total AL bioactivity for PFS and DCR is 14.48 to 65.8 µg/ml, and for overall survival is 10.97 to 65.8 µg/ml. Conclusions: The predictors of ICC disease prognosis were established based on the pharmacokinetics of total AL bioactivity. The information could be exploited to improve the clinical efficacy of AL in patients with advanced-stage ICC. These predictors will be validated in a phase 2B clinical study.

Trial registration: TCTR20210129007 (TCTR: www.clinicaltrials.in.th).

Background: Cancer cachexia is a common debilitating weight loss syndrome in advanced cancer, particularly lung cancer. Omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, with their immune-modulating effects, have been used to improve the nutritional status of patients with cancer cachexia.

Aim: Evaluate the effects of omega-3 fatty acids in change in weight and lean body/skeletal mass, and health-related quality of life scores (HRQoL) in patients with advanced non-small cell lung cancer and cancer cachexia.

Design and data sources: Clinical trials from electronic databases and unpublished literature (date of last search 20 December 2023) were independently reviewed and evaluated by authors for their methodological quality. Data from eligible trials were extracted and analyzed in a meta-analysis.

Results: Six trials were included. Five trials (354 patients) assessed change in weight; 2 trials (132 patients) assessed change in lean body/skeletal mass and HRQoL scores (Global Health and Physical Functioning subscales). There is a significant difference in change in weight (mean difference [MD]: 1.22, 95% CI: 1.05-1.38, P < .01) and HRQoL scores (Global Health [MD: 14.40, 95% CI: 9.22-19.59, P < .01] and Physical Functioning [MD: 10.38, 95% CI: 8.50-12.27, P < .01] subscales) favoring the omega-3 fatty acids group. The change in lean body/skeletal mass is not significant (MD: 2.05, 95% CI: -0.55 to 4.66, P = .12).

Conclusions: Among patients with advanced non-small cell lung cancer and cancer cachexia, supplementation with omega-3 fatty acids leads to a significant increase in weight and HRQoL scores but not in change in lean body/skeletal mass.

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most prevalent and distressing side effects of chemotherapy among patients with cancer worldwide. Despite continuing advances in antiemetic medicines, nausea and vomiting associated with cancer chemotherapy remain a substantial therapeutic concern for many patients. However, P6 and Auricular acupressure (AA) have been recognized as potential therapy for managing chemotherapy-induced nausea and vomiting.

Aim: This study aimed to evaluate the effectiveness of P6 and Auricular acupressure (AA) in reducing chemotherapy-induced nausea and vomiting among patients with cancer. And to explore a prominent and effective evidence-based protocol for implementing acupressure to treat chemotherapy-induced nausea and vomiting.

Method: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Several databases were used to search for eligible studies using specific keywords. Only systematic reviews and clinical trials on acupressure for managing CINV among adults with cancer were included. This review covered articles published in English from 2015 to 2022.

Results: A total of 14 published studies were included in this review study; 10 articles were trial studies, and the other 4 were systematic review and meta-analysis studies. The quality of 10 included clinical trials were assessed using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for quantitative studies, the overall result showed that 40% of study rated with moderate quality, no study was rated with low quality, and (60%) studies rated as high-quality study. As well as the quality assessment of all review studies showed that the majority of included systematic reviews and meta-analysis with a low risk of bias and high to moderate power of evidence. In all included studies the acupressure was utilized as a primary complementary intervention for chemotherapy induced nausea and vomiting. The result of this extensive and comprehensive review the P6 and auricular acupressure is an effective complementary therapy in reducing and controlling chemotherapy-induced nausea and vomiting among participants with various types of cancer and receiving various types of chemotherapy.

Conclusion: The successful and effective application of acupressure in managing CINV for certain types of cancer had been supported in previous literature as a safe, affordable, and non-invasive alternative to pharmaceutical medications. However, standardization guidelines regarding the use of acupressure independently or in combination with other pharmacological therapies to address CINV in various cancers require immediate attention.

Background: Ginsenosides (GS), including total GS, Rh2, Rg3 and compound K (CK), have been utilized as adjuvants in transarterial chemoembolization (TACE), surgery, and chemotherapy for hepatocellular carcinoma (HCC) therapy. However, the safety and efficacy of such combination treatments have been contradictory across different studies. This study aims to systematically evaluate the efficacy and safety of GS as adjuvant therapy for HCC. Methods: A literature search of PubMed, CNKI, Wanfang Data, Cochrane Library, Embase, and Web of Science was conducted up to May 2024 for clinical randomized controlled trials (RCTs) on GS-based adjuvant treatments for HCC. Two researchers independently screened the literature, extracted relevant data, and assessed study quality. Meta-analysis was conducted using RevMan 5.4. Results: Nineteen articles involving 1448 patients were included. Meta-analysis showed that GS as an adjuvant therapy for HCC improved disease control rate (risk ratio (RR) = 1.42, 95% CI [1.26, 1.60]), objective response rate (RR = 1.20, 95% CI [1.09, 1.32]), life quality (RR = 1.49, 95% CI [1.23, 1.79]), 1-year overall survival rate (RR = 1.27, 95% CI [1.06, 1.52]), 2-year overall survival rate (RR = 1.43, 95% CI [1.06, 1.95]), ehanced Child-Pugh in A level (RR = 1.59, 95% CI [1.08, 2.34]), Child-Pugh in B level (RR = 1.28, 95% CI [1.08, 1.52]); increased CD3⁺ (MD = 8.81, 95% CI [3.91, 13.71]), NKC (MD = 8.00, 95% CI [6.76, 9.24]) and CD4⁺ (MD = 9.38, 95% CI [8.04, 10.72]), and reduced incidence of adverse reactions including nausea and vomiting (RR = 0.66, 95% CI [0.57, 0.77]), anorexia (RR = 0.33, 95% CI [0.21, 0.50]), leukopenia (RR = 0.55, 95% CI [0.46, 0.67]) and myelosuppression (RR = 0.54, 95% CI [0.40, 0.74]); decreased Child-Pugh in C level (RR = 0.43, 95% CI [0.27, 0.68]) and CD4⁺/CD8⁺ ratio (MD = 0.50, 95% CI [0.47, 0.57]). Conclusions: In summary, GS combined with Western medical approaches (TACE, surgery, chemotherapy) for the treatment of HCC can improve clinical efficacy, increase overall survival rates, enhance patient life quality, and reduce the occurrence of adverse reactions. However, due to the generally low quality of the included studies, more large-sample, multi-center, high-quality, RCTs are warranted to further consolidate these findings.