Tumor treating fields for newly diagnosed high-grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center.

BACKGROUND AND OBJECTIVE: High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. METHODS: We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. RESULTS: There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. CONCLUSIONS: In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Comparison of embryo quality and pregnancy outcomes for patients with low ovarian reserve in natural cycles and mildly stimulated cycles: a cohort study.

BACKGROUND: As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles. METHODS: This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles. RESULTS: The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00. CONCLUSION: Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.

In the realm of in-vitro fertilisation (IVF) treatment, women with low ovarian reserve often face the crucial decision of opting for natural or mildly stimulated cycles. This retrospective study, conducted between January 2017 and April 2021 at Guangdong Second Provincial General Hospital, delves into the impact of these cycles on pregnancy outcomes. Examining 478 natural cycles and 448 mildly stimulated cycles, the study reveals a notably higher pregnancy rate in the natural cycle group (51.8% vs. 40.1%). Additionally, natural cycles demonstrated higher rates of available embryos, high-quality embryos, and oocyte utilisation compared to their mildly stimulated counterparts. The findings suggest that natural cycles, with proper oocyte retrieval timing, could be a favourable choice for those with low ovarian reserve seeking IVF treatment.

Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes.

Mammalian centromeres are generally composed of dispersed repeats and the satellites such as α-satellites in human and major/minor satellites in mouse. Transcription of centromeres by RNA polymerase II is evolutionary conserved and critical for kinetochore assembly. In addition, it has been found that the transcribed satellite RNAs can bind DNA repair proteins such as MRE11 and PRKDC, and excessively expressed satellite RNAs could induce genome instability and facilitate tumorigenesis. During the maturation of female oocyte, centromeres are critical for accurate segregation of homologous chromosomes and sister chromatids. However, the dynamics of oocyte centromere transcription and whether it associated with DNA repair proteins are unknown. In this study, we found the transcription of centromeres is active in growing oocytes but it is silenced when oocytes are fully grown. DNA repair proteins like Mlh1, Mre11 and Prkdc are found associated with the minor satellites and this association can be interfered by RNA polymerase II inhibitor α-amanitin. When the growing oocyte is in vitro matured, Mlh1/Mre11/Prkdc foci would release from centromeres to the ooplasm. If the oocytes are treated with Mre11 inhibitor Mirin, the meiosis resumption of growing oocytes with Mre11 foci can be suppressed. These data revealed the dynamic of centromeric transcription in oocytes and its potential association with DNA repair proteins, which provide clues about how oocytes maintain centromere stability and assemble kinetochores.

A long-acting recombinant FSH supports high-quality mouse follicle development and oocyte maturation in vitro by coordinating somatic and germ cell transcriptomes.

Strategies to maximize individual fertility chances are constant requirements of ART. In vitro folliculogenesis may represent a valid option to create a large source of immature ovarian follicles in ART. Efforts are being made to set up mammalian follicle culture protocols with suitable FSH stimuli. In this study, a new type of recombinant FSH (KN015) with a prolonged half-life is proposed as an alternative to canonical FSH. KN015 supports the in vitro development of mouse follicles from primary to preovulatory stage with higher efficiency than canonical FSH and enhanced post-fertilization development rates of the ovulated oocytes. The use of KN015 also allows us to compare the dynamic transcriptome changes in oocytes and granulosa cells at different stages, in vivo and in vitro. In particular, KN015 facilitates mRNA accumulation in growing mouse oocytes and prevents spontaneous luteinization of granulosa cells in vitro. Novel analyses of transcriptome changes in this study reveal that the in vivo oocytes were more efficient than in vitro oocytes in terms of maternal mRNA clearing during meiotic maturation. KN015 promotes the degradation of maternal mRNA during in vitro oocyte maturation, improves cytoplasmic maturation and, therefore, enhances embryonic developmental potential. These findings establish new transcriptome data for oocyte and granulosa cells at the key stages of follicle development, and should help to widen the use of KN015 as a valid and commercially available hormonal support enabling optimized in vitro development of follicles and oocytes.

Continuous light exposure influences luteinization and luteal function of ovary in ICR mice.

With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD). We used continuous light-exposed mice as a model to observe whether continuous light exposure may affect luteinization and luteal function. We showed that the level of progesterone in serum reduced (p < .001), the number of corpus luteum (CL) decreased (p < .01), and the expressions of luteinization-related genes (Lhcgr, Star, Ptgfr, and Runx2), clock genes (Clock and Per1), and Mt1 were downregulated (p < .05) in the ovaries of mice exposed to continuous light, suggesting that continuous light exposure induces defects in luteinization and luteal functions. Strikingly, injection of melatonin (3 mg/kg) could improve luteal functions in continuous light-exposed mice. Moreover, we found that, after 2 h of hCG injection, the level of pERK1/2 in the ovary decreased in the continuous light group, but increased in the melatonin administration group, suggesting that melatonin can improve LPD caused by continuous light exposure through activating the ERK1/2 pathway. In summary, our data demonstrate that continuous light exposure affects ovary luteinization and luteal function, which can be rescued by melatonin.

Genome-wide map of R-loops reveals its interplay with transcription and genome integrity during germ cell meiosis.

INTRODUCTION: The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics. OBJECTIVES: Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process. METHODS: In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry. RESULTS: R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage. CONCLUSION: The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis.

Diagnostic and Prognostic Value of Dysregulated miR-10a-3p in Patients with Severe Pneumonia.

Purpose: Previous studies have shown that microRNA is involved in regulating a variety of human inflammatory diseases. The purpose of this study was to investigate the expression of miR-10a-3p in the blood of patients with severe pneumonia and evaluate its value in the diagnosis and prognosis of severe pneumonia. Patients and Methods: Seventy patients with severe pneumonia and 75 healthy individuals were included in this study. Venous blood of all subjects was obtained for RT-qPCR analysis to obtain the relative expression level of miR-10a-5p. The diagnostic accuracy of miR-10a-5p for severe pneumonia was assessed by ROC curve. After standardized treatment, the prognosis of patients with severe pneumonia was analyzed by a 28-day follow-up method. Kaplan-Meier curve and multivariate Cox regression analysis were used to determine the basic factors influencing the prognosis of patients. Results: Compared with healthy control, serum miR-10a-3p expression in patients with severe pneumonia was distinctly upregulated (P < 0.001). Besides, ROC analysis showed that miR-10a-3p had high diagnostic accuracy for severe pneumonia, with an AUC of 0.881, sensitivity and specificity of 75.7% and 84.0%, respectively. Kaplan-Meier curve exhibited that high miR-10a-3p expression group had a higher probability of death than those with low miR-10a-3p expression. Multivariate Cox regression analysis demonstrated that miR-10a-3p and CRP were independent risk factors affecting the prognosis of patients. Conclusion: The expression of miR-10a-3p was increased in patients with severe pneumonia, and abnormally expressed miR-10a-3p has the potential to be used as a diagnostic and prognostic marker for severe pneumonia, which provides a new biological direction for the early detection and risk assessment of severe pneumonia.

PSMG2-controlled proteasome-autophagy balance mediates the tolerance for MEK-targeted therapy in triple-negative breast cancer.

Although the MAPK pathway is aberrantly activated in triple-negative breast cancers (TNBCs), the clinical outcome of MEK-targeted therapy is still poor. Through a genome-wide CRISPR-Cas9 library screening, we find that inhibition of PSMG2 sensitizes TNBC cells BT549 and MB468 to the MEK inhibitor AZD6244. Mechanistically, PSMG2 knockdown impairs proteasome function, which in turn activates autophagy-mediated PDPK1 degradation. The PDPK1 degradation significantly enhances AZD6244-induced tumor cell growth inhibition by interrupting the negative feedback signals toward the AKT pathway. Consistently, co-targeting proteasomes and MEK with inhibitors synergistically suppresses tumor cell growth. The autophagy inhibitor chloroquine partially relieves the PDPK1 degradation and reverses the growth inhibition induced by combinatorial inhibition of MEK and proteasome. The combination regimen with the proteasome inhibitor MG132 plus AZD6244 synergistically inhibits tumor growth in a 4T1 xenograft mouse model. In summary, our study not only unravels the mechanism of MEK inhibitor resistance but also provides a combinatorial therapeutic strategy for TNBC in clinics.

Role of Estrogen Receptor-Positive/Negative Ratios in Regulating Breast Cancer.

The alpha estrogen receptor (ERα) contributes to breast cancer progression and recent guidelines define ER positivity as ≥1% stained cells, and a few tumor tissues show no ERα expression at all or are at 100%. Although ER and aromatase inhibitors are widely used to treat hormone receptor-positive (HR+) breast cancer, their effect on tumor activity at different ERα levels remains unclear. Therefore, we investigated the role of ERα+/ERα- ratios in determining the ERα level. We used ERα stably transfected and wild-type MDA-MB-231 cells (MDA-MB-231Trans-ER and MDA-MB-231WT, respectively) as represented ER+ and ER- cells, respectively, and MCF-7 cells were the positive control. MDA-MB-231Trans-ER and MDA-MB-231WT cells were mixed and cocultured at a ratio of 0%, 20%, 40%, 70%, and 100%. Migration and invasion functions at different cell ratios were evaluated in vitro using the Transwell and scratch test. In a xenograft mouse model, the polarization of the tumor-associated (M2) macrophage and the expression of breast cancer gene 1 (BRCA1), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and tumor necrosis factor (TNF)-α were measured. The results showed that the cell invasion and migration were significantly higher at 40% and 70% than they were at other ratios. Additionally, in vivo, the 70% ERα+/ERα-ratio was a critical indicator of cell activity and cytokine expression. The highest M2 level and expression of VEGR, TNF-α, BRCA1, and HER2 were shown at a ratio of 70%. Moreover, the effects of ERα were not linear in breast cancer, indicating that the ERα status requires continuous monitoring during long-term endocrine treatment. These results indicate that during HR+ breast cancer treatment, the ERα+/ERα- ratio may be a useful predictor and should be evaluated further.

[A Rare Case of Extremely High Counts of EpCAM + Circulating Tumor Cells and Circulating Tumor Microemboli Detected in a Patient with Small Cell Lung Cancer].

A 77-year-old man was admitted at our hospital due to "generalized increase in the number of masses and enlargement of the masses observed for one month". Combined assessment of the imaging (computed tomography and magnetic resonance imaging) findings and results of lung centesis biopsy and liquid biopsy suggest that the patient had small cell lung cancer of the left upper lobe, with right hilar, mediastinal, bilateral axillary, abdominal and retroperitoneal lymph node metastases, as well as widespread subcutaneous soft tissue, liver, bilateral adrenal, bilateral kidneys and multiple brain metastases (extensive stage). In order to obtain an evaluation of the development of the disease as soon as possible, the circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) in 6 mL peripheral blood were examined by subtraction enrichment-immunostaining fluorescence in situ hybridization (SE-iFISH) technology. A total of 919 epithelial cell adhesion molecule (EpCAM)-positive CTCs and 61 EpCAM-positive CTM were identified. Among them, there were 14 haploid CTCs (1.52%), 788 diploid CTCs (85.75%), 44 triploid CTCs (4.79%), 70 tetraploid CTCs (7.62%) and 3 pentaploid or higher-fold polyploid CTCs (0.33%). Herein, we reported a rare case with extremely high accounts of CTCs and CTM and positive findings for tumor markers, which was identified for the first time. The examination of CTCs by SE-iFISH contributed to the diagnosis, prognosis and treatment evaluation of cancer and facilitated the formulation of precise and individualized therapeutic regime.

Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging.

A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrates a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance is also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) is high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, causes ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.

Case Report: Rare Systemic and Aggressive ALK-Positive Histiocytosis With Recurrent Pancreatitis Treating by Alectinib.

ALK-positive histiocytosis (APH) is a rare and recently described, solitary or generalized, histiocytic proliferative disorder with a characteristic gene translocation involving the fusion of the ALK gene at chromosome 2p23. To date, only 25 cases of APH have been reported. The patient presented with multiple nodules in the lung, liver, gallbladder, pancreas, kidney, and skin rashes, along with recurrent pancreatitis and cholecystitis. The histiocytes from the lesion were positive for CD68 and ALK and negative for S100 and CD1α. A reduced dose of the ALK inhibitor alectinib was administered rather than the standard dose of alectinib or chemotherapy because of recurrent pancreatitis, which has not been previously reported in APH cases. After 18 months of follow-up, the patient was maintained on alectinib, and a partial response (PR) was achieved.

Methodology for designing intrahospital transportation of patients with suspected infectious disease that limits infection spread risk in China.

Aims: The transport of patients suspected of having COVID-19 requires careful consideration. Using paths selected at random and not accounting for person flow along the path are risk factors for infection spread. Intrahospital transportation (IHT) protocols and guidelines should be used to help reduce the risk of secondary virus transmission during transport. This study aimed to propose optimal IHT for patients with an infectious disease presenting in an out-patient area. Design: The map of a West China Hospital was used. We also used field investigation findings and simulated person flow to establish pathway length and transportation time. We identified three optimum pathways and estimated safety boundary marks, including a patient transportation border (PTB) and safety transportation border (STB). Finally, IHT, PTB, and STP formed a virtual transport pipeline (VTP) and a traceable IHT management system, which can generate a virtual isolation space. Results: The three pathways met efficiency, accessibility, and by-stander flow criteria. No facility characteristic modification was required. Conclusions: Using virtual models to identify pathways through out-patient hospital areas may help reduce the risk of infection spread.

Effects of a Chlorogenic Acid-Containing Herbal Medicine (LASNB) on Colon Cancer.

BACKGROUND: Plant polyphenols, which contain phenolic acids such as chlorogenic acid (CGA), can be used for the treatment of gastrointestinal cancer and have gained increasing attention in recent years. In this study, we explored a novel CGA-containing herbal medicine named LASNB, which was extracted from Lonicera japonica Thunb., Agrimonia eupatoria L., and Scutellaria barbata D.Don. METHODS: CGA in LASNB was analyzed using high-performance liquid chromatography (HPLC). The biological functions and molecular mechanisms of LASNB were investigated in colon cancer cell lines (HCT116, HCT15, and CT26), a normal colon cell line (NCM460), and a CT26 xenograft model. To assess safety, hematological toxicity and pathology of the liver, kidney, and lung were evaluated. RESULTS: LASNB suppressed HCT116, HCT15, and CT26 colon cancer progression by inhibiting proliferation capacity, promoting cell apoptosis, and suppressing cell migration both in vitro and in vivo. Investigation into the underlying molecular mechanism indicated that LASNB suppressed the activation of receptor tyrosine kinase- (RTK-) MEK-ERK and NF-κB pathways. With regard to safety, slight interstitial vascular congestion in the lung was observed, but no severe pathological or hematological toxicity was detected. CONCLUSIONS: We found that LASNB suppressed the progression of colon cancer via the RTK-MEK-ERK and NF-κB pathways, with no severe toxicity observed. Therefore, LASNB has the potential to be used as a supplementary herbal medicine for the treatment of colon cancer.

Local treatment of metastases plus systemic chemotherapy on overall survival of patients with metastatic nasopharyngeal carcinoma.

BACKGROUND: To investigate the effect of local treatment of metastases on overall survival (OS) of patients with metastatic nasopharyngeal carcinoma (NPC). METHODS: One hundred and forty-seven patients were included. The association between local treatment and OS was examined with propensity score matching (PSM) method. RESULTS: In entire cohort, the median OS was significantly longer in patients with local treatment of metastases plus chemotherapy compared to those with chemotherapy alone (71.7 vs. 16.2 months; p < 0.001). In PSM cohort, similar OS benefit of patients with local treatment was observed (55.6 vs. 17.6 months; p = 0.011). The survival benefit of local treatment remained regardless of the number of metastatic lesions and metastatic sites. Patients received radiation doses of >60 Gy had longer OS than those who received less. CONCLUSIONS: Local treatment of metastases could improve OS of patients with metastatic NPC and could be considered in their treatment in addition to chemotherapy.

Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes.

During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.

Synchronous Metastatic Nasopharyngeal Carcinoma: Characteristics and Survival of Patients Adding Definitive Nasopharyngeal-Neck Radiotherapy to Systematic Chemotherapy.

PURPOSE: To determine the M1 sub-staging in synchronous metastatic nasopharyngeal carcinoma (smNPC) and to examine the effect of nasopharyngeal-neck radiotherapy (RT) and local treatment of metastases on overall survival (OS) of smNPC patients. PATIENTS AND METHODS: A total of 150 patients with smNPC were included. Metastatic characteristics associated with their potential prognostic significance were analyzed. Then, a stratification system of the M1 sub-staging in smNPC was provided according to metastatic features. Moreover, the OS of patients with or without nasopharyngeal-neck RT was compared by Log rank test. The OS of patients who received or did not receive local treatment of metastases was also analyzed. RESULTS: We successfully divided the M1 stage into three sub-staging: M1a (a single site with a single lesion), M1b (a single site with multiple lesions), and M1c (multiple sites with multiple lesions). The median OS was 53.2, 25.8, and 18.9 months for M1a, M1b, and M1c, respectively (p < 0.001). Nasopharyngeal-neck RT plus systematic chemotherapy (CT) significantly improved OS compared to systematic CT (median OS, 34.0 vs 15.2 months, p = 0.002). However, incorporation of local treatment of metastases did not bring survival benefit to smNPC patients who received nasopharyngeal-neck RT plus systematic CT (median OS, 25.8 vs 35.1 months, p = 0.374). CONCLUSION: The sub-staging of the M1 stage in smNPC had promising prognostic value. Adding nasopharyngeal-neck RT on the basis of systematic CT markedly improved the survival of smNPC patients, while addition of local treatment of metastases to nasopharyngeal-neck RT plus systematic CT for smNPC needed further exploration.

Study on the Anticancer Effect of an Astragaloside- and Chlorogenic Acid-Containing Herbal Medicine (RLT-03) in Breast Cancer.

BACKGROUND: Although surgery, chemotherapy, radiotherapy, and endocrine therapy are widely used in clinical practice for breast cancer treatment, herbal medicines (HMs) are considered as an alternative to palliative treatments because of their coordinated intervention effects and relatively low side effects. Astragaloside (AS) and chlorogenic acid (CGA) are major active ingredients of Radix Astragali and Lonicera japonica, which have shown antitumorigenic properties in certain cancers, but the role of HMs containing both AS and CGA remains unclear in breast cancer. In this study, we explored an AS- and CGA-containing HM (RLT-03) extracted from Radix Astragali, Lonicerae Japonicae Flos, Trichosanthin, and Rhizoma imperatae. METHODS: RLT-03 was extracted using water and n-butanol, and the AS and CGA ingredients in RLT-03 were identified by high-performance liquid chromatography (HPLC) and evaporative light-scattering detector (ELSD). 4T1, EMT6, BT-549, and MDA-MB-231 breast cancer cell lines were used, and an EMT6 xenograft model was established. Cell proliferation, migration, and apoptosis were measured in vitro, and tumor volume and weight were observed in vivo. The expression of VEGF, EGF, IL-10, TGF-ß, and CD34 and cell apoptosis in tumors were examined. RESULTS: RLT-03 inhibited cell viability and induced apoptosis in a dose- and time-dependent manner. In vivo, tumor volume and weight were reduced, and the expression of VEGF, EGF, IL-10, TGF-ß, and CD34 was suppressed in the tumor microenvironment, while cell apoptosis was induced. CONCLUSION: RLT-03 exhibited therapeutic effects against breast cancer by regulating the expression of ligands of receptor tyrosine kinases (RTKs) and inflammatory factors. Thus, RLT-03 represents a potential supplementary HM that can be used in breast cancer therapy.