Effectiveness of Chinese Herbal Medicine as a Complementary Treatment for Neutropenia Prevention and Immunity Modulation During Chemotherapy in Patients With Breast Cancer: Protocol for a Real-World Pragmatic Clinical Trial.

BACKGROUND: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE: This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS: We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS: This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS: Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55662.

Pueraria mirifica inhibits 17ß-estradiol-induced cell proliferation of human endometrial mesenchymal stem cells.

OBJECTIVE: The notion that the human endometrium may contain a population of stem cells has recently been proposed. The mesenchymal stem cells (MSCs) in the endometrium are believed to be responsible for the remarkable regenerative ability of endometrial cells. Estrogens influence the physiological and pathological processes of several hormone-dependent tissues, such as the endometrium. Pueraria mirifica (PM) is a herbal plant that contains several phytoestrogens, including isoflavones, lignans, and coumestans, and is known to exert an estrogenic effect on animal models. The present study investigated the effects of PM on the proliferation of human endometrial MSCs (hEN-MSCs). MATERIALS AND METHODS: The hEN-MSCs were isolated from human endometrial tissue. The surface markers of these hEN-MSCs were identified through reverse transcription-polymerase chain reaction analysis. The proliferation potential of hEN-MSCs was measured through a cell proliferation assay. Multilineage differentiation ability was confirmed through Oil red O and von Kossa staining. RESULTS: This study demonstrated that 17ß-estradiol-responsive MSCs with Oct-4, CD90, and CD105 gene expression can be derived from the human endometrium and that PM exerts biological effects on hEN-MSCs, specifically, enhanced cell growth rate, through the estrogen receptor. Furthermore, PM at 1500 and 2000 µg/mL significantly increased cell proliferation compared with the vehicle control, and PM concentration at 1000 µg/mL significantly inhibited the enhanced cell growth rate induced by 17ß-estradiol in hEN-MSCs. CONCLUSION: This study provides new insights into the possible biological effects of PM on the proliferation of hEN-MSCs.

Bisphenol A at environmentally relevant doses induces cyclooxygenase-2 expression and promotes invasion of human mesenchymal stem cells derived from uterine myoma tissue.

OBJECTIVE: Uterine myoma is the most common benign reproductive tract tumor in women. Despite its high prevalence, the exact pathogenesis of these benign tumors remains unknown. Toward understanding the pathogenic mechanism of these tumors, we attempted to isolate human uterine myoma mesenchymal stem cells (hUM-MSCs), which may be the target cells for tumorigenesis. Furthermore, we tested the response of these hUM-MSCs to the environmental endocrine disruptor, bisphenol A (BPA), which may mimic the action of estrogen in hormone-sensitive organs such as the uterus. MATERIALS AND METHODS: The hUM-MSC lines were clonally derived from uterine myoma tissue using the MSU-1 medium supplemented with N-acetyl-l-cysteine and l-ascorbic acid-2-phosphate. These hUM-MSCs were characterized by reverse transcription polymerase chain reaction (RT-PCR) analysis for the expression of mesenchymal stem cell (MSC) surface markers (e.g., CD90 and CD105) and the transcription factor Oct-4. The proliferation potential was measured by the cumulative population doubling level and the colony-forming efficiency. RESULTS: Putative hUM-MSC lines expressed CD90, CD105, and the stem cell marker gene, Oct-4. The cells were capable of differentiating into adipocytes, osteoblasts, and chondrocytes. Bisphenol A treatment of these hUM-MSCs enhanced cell proliferation and colony-forming efficiency in a dose-responsive manner. At an environmentally relevant concentration (10(-8) M), BPA moreover induced cyclooxygenase-2 (COX-2) gene expression and promoted cell migration and invasiveness. CONCLUSION: The hUM-MSC cell lines can be isolated from uterine myoma tissues. Bisphenol A could enhance cell proliferation and colony-forming efficiency, induce COX-2 gene expression, and promote migration and invasion of hUM-MSCs. The results imply that BPA has a detrimental effect on female health by promoting uterine tumorigenesis.

Optimizing proliferation and characterization of multipotent stem cells from porcine adipose tissue.

Porcine mesenchymal stem cells have been isolated previously from bone marrow but not from adipose tissue. In the present study a new cell-culture method, using a low-calcium medium supplemented with N-acetyl-L-cysteine and L-ascorbic acid 2-phosphate (the PM2 medium) was developed to grow pASCs (porcine adipose-tissue-derived stem cells). The pASCs developed using the new medium showed a high growth rate and a high proliferation potential, as measured by a cumulative population doubling level (55) that was significantly higher than those reported for ASCs in the literature. These pASCs lacked gap-junctional intercellular communication and were capable of differentiation into three mesodermal lineages (i.e. adipocytes, osteoblasts and chondrocytes) and an ectodermal lineage (i.e. neural cells). Surprisingly, osteogenic ability, but not adipogenesis, was found to increase dramatically with increasing passages. The high proliferative and differentiation potential of these pASCs should facilitate the development of a large-animal model to study the use of ASCs in regenerative and reparative medicine.