The Effect and Mechanism of Astragalus Polysaccharides on T Cells and Macrophages in Inhibiting Prostate Cancer.

BACKGROUND: The impact and underlying mechanisms of astragalus polysaccharide (APS) on prostate cancer, particularly its role in immunomodulation, remain inadequately elucidated. METHODS: This study employed the XTT assay for assessing proliferation in prostate cancer cells and macrophages. T cell proliferation was determined using the Carboxyfluorescein diacetate succinimidyl ester labeling assay. APS's effect on T cells and macrophages was scrutinized via flow cytometry, Western blot analysis, ELISA, quantitative PCR and cytokine membrane arrays. The effect of APS on interaction between PD-L1 and PD-1 was investigated by the PD-L1/PD-1 homogeneous assay. Additionally, the impact of conditioned medium from T cells and macrophages on PC-3 cell migration was explored through migration assays. RESULTS: It was observed that APS at concentrations of 1 and 5 mg/mL enhanced the proliferation of CD8+ T cells. At a concentration of 5 mg/mL, APS activated both CD4+ and CD8+ T cells, attenuated PD-L1 expression in prostate cancer cells stimulated with interferon gamma (IFN-γ) or oxaliplatin, and moderately decreased the population of PD-1+ CD4+ and PD-1+ CD8+ T cells. Furthermore, APS at this concentration impeded the interaction between PD-L1 and PD-1, inhibited the promotion of prostate cancer migration mediated by RAW 264.7 cells, THP-1 cells, CD4+ T cells, and CD8+ T cells, and initiated apoptosis in prostate cancer cells treated with conditioned medium from APS (5 mg/mL)-treated CD8+ T cells, RAW 264.7 cells, or THP-1 cells. CONCLUSION: The findings indicate a potential role of 5 mg/mL APS in modulating the PD-1/PD-L1 pathway and influencing the immune response, encompassing T cells and macrophages. Consequently, further in vivo research is recommended to assess the efficacy of APS.

Induction of ferroptosis and apoptosis in endometrial cancer cells by dihydroisotanshinone I.

Danshen, also known as Salvia miltiorrhiza, is a medicinal herb used in traditional Chinese medicine. Its potential impact on endometrial cancer has not been thoroughly investigated. This study aimed to examine the effect of dihydroisotanshinone I (DT), a compound found in Danshen, on the viability of ARK1 and ARK2 endometrial cancer cells and its mechanisms. The results showed that 10 µM DT inhibited cell viability of ARK1 and ARK2 cells by inducing apoptosis and ferroptosis, which was achieved by blocking the expression of GPX4. In vivo experiments using a xenograft nude mouse model indicated that DT treatment significantly reduced tumor volume without causing any adverse effects. These findings suggest that DT may be a potential therapeutic agent for inhibiting endometrial cancer cell viability, but further research is needed to confirm these results.

Dihydroisotanshinone I and BMAL-SIRT1 Pathway in an In Vitro 6-OHDA-Induced Model of Parkinson's Disease.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.

The Role of MRE11 in the IL-6/STAT3 Pathway of Lung Cancer Cells.

MRE11 is a pivotal protein for ATM activation during double-strand DNA break. ATM kinase activations may act as lung cancer biomarkers. The IL-6/STAT3 pathway plays an important role in tumor metastasis, including lung cancer. However, the mechanism between MRE11 and the IL-6/STAT3 pathway is still unclear. In this study, we discovered that MRE11 can interact with STAT3 under IL-6 treatment and regulate STAT3 Tyr705 phosphorylation. After the knockdown of MRE11 in lung cancer cells, we discovered that IL-6 or the conditional medium of THP-1 cells can induce the mRNA expression of STAT3 downstream genes, including CCL2, in the control cells, but not in MRE11-knockdown lung cancer cells. Moreover, CCL2 secretion was lower in MRE11-knockdown lung cancer cells than in control cells after treatment with the conditional medium of RAW264.7 cells. In addition, MRE11 deficiency in lung cancer cells decreases their ability to recruit RAW 264.7 cells. Furthermore, MRE11 is a potential target for lung cancer therapy.

Nasal irrigation with licorice extract (Glycyrrhiza glabra) in treating nasal polyps by reducing fibroblast differentiation and extracellular matrix production in TGF-ß1-stimulated nasal polyp-derived fibroblasts by inhibiting the MAPK/ERK-1/2 pathway - an in vitro and in clinic study.

BACKGROUND: To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs. HYPOTHESIS/PURPOSE: This study investigated the mechanism of LE on NPs. STUDY DESIGN: NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured. METHODS: The TGF-ß1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway. RESULTS: Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-ß1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion. CONCLUSION: LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway. TRIAL REGISTRATION: ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529.

The difference in pathogenic bacteria between chronic rhinosinusitis in patients with and without Sjogren's syndrome: a retrospective case-control study.

BACKGROUND: Chronic rhinosinusitis (CRS) affects the quality of life of many people worldwide and can cause comorbidities. Our previous research proved that Sjogren's syndrome (SS) is a predisposing factor for CRS, with a 2.5-fold associated risk. Antibiotics are important in CRS treatment; however, there is a paucity of research on the pathogenic bacteria of SS-CRS in the past. We conducted this study to investigate the pathogenic difference of SS-CRS and non-SS-CRS and aimed to give clinicians references when selecting antibiotics to treat SS-CRS. MATERIALS AND METHODS: A total of 14,678 patients hospitalized for CRS operation from 2004 to 2018 were identified from the Chang Gung Research Database. These CRS cases were classified as either SS-CRS or non-SS-CRS. We analyzed their bacterial distribution by studying the results of the pus cultures performed alongside surgery. RESULTS: The top three facultative anaerobic or aerobic isolated bacteria in the SS-CRS group were coagulase-negative Staphylococcus (CoNS: 34.3%), Pseudomonas aeruginosa (28.6%), methicillin-sensitive Staphylococcus aureus (MSSA: 20%), and Staphylococcus epidermidis (20%). In the non-SS-CRS group, S. epidermidis (29.3%), CoNS (25.7%), and MSSA (14.2%) were identified. The top three anaerobic bacterial genera were Cutibacterium (54.3%), Peptostreptococcus (11.4%), and Fusobacterium (11.4%) in the SS-CRS group and Cutibacterium (53.8%), Peptostreptococcus (25%), and Prevotella (12.9%) in the non-SS-CRS group. CONCLUSIONS: P. aeruginosa is a major pathogen in SS-CRS patients. In addition, physicians should be aware of potential Fusobacterium and antibiotic-resistant bacterial infection in patients with SS-CRS.

The Pathogenic Bacteria of Deep Neck Infection in Patients with Type 1 Diabetes, Type 2 Diabetes, and Without Diabetes from Chang Gung Research Database.

Deep neck infection (DNI) is a lethal emergent condition. Patients with types 1 and 2 diabetes mellitus (T1DM and T2DM, respectively) are predisposed to DNI and have poorer prognoses. The mainstay of the treatment is surgical drainage and antibiotics; however, the pathogenic bacteria of T1DM-DNI have not been studied before. We obtained the data of 8237 patients with DNI who were hospitalized from 2004 to 2015 from the Chang Gung Research Database, which contains multi-institutional medical records in Taiwan. Using diagnostic codes, we classified them into T1DM-DNI, T2DM-DNI, and non-DM-DNI and analyzed their pathogenic bacteria, disease severity, treatment, and prognosis. The top three facultative anaerobic or aerobic bacteria of T1DM-DNI were Klebsiella pneumoniae (KP, 40.0%), Viridans Streptococci (VS, 22.2%), and methicillin-sensitive Staphylococcus aureus (MSSA, 8.9%), similar for T2DM (KP, 32.2%; VS, 23.3%; MSSA, 9.5%). For non-DM-DNI, it was VS (34.6%), KP (9.8%), and coagulase-negative Staphylococci (8.7%). The order of anaerobes for the three groups was Peptostreptococcus micros, Prevotella intermedia, and Peptostreptococcus anaerobius. Patients with T1DM-DNI and T2DM-DNI had higher white blood cell (WBC) counts and C-reactive protein (CRP) levels, more cases of surgery, more cases of tracheostomy, longer hospital stays, more mediastinal complications, and higher mortality rates than those without DM-DNI. Patients in the death subgroup in T1DM-DNI had higher WBC counts, band forms, and CRP levels than those in the survival subgroup. Patients with DM-DNI had more severe disease and higher mortality rate than those without DM-DNI. KP and Peptostreptococcus micros are the leading pathogens for both patients with T1DM-DNI and those with T2DM-DNI. Clinicians should beware of high serum levels of infection markers, which indicate potential mortality.

Dihydroisotanshinone I as a Treatment Option for Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of the head and neck, and their prevalence is rapidly increasing. HNSCCs present a clinical challenge because of their high recurrence rate, therapeutic resistance to radiation and chemotherapy drugs, and adverse effects. Hence, traditional Chinese herbal treatment may be advantageous to therapeutic strategies for HNSCCs. Danshen (Salvia miltiorrhiza), a well-known Chinese herb, has been extensively applied in treatments for various diseases, including cancer, because of its high degree of safety and low rate of adverse effects despite its unclear mechanism. Thus, we aimed to explore the possible anticancer effects and mechanisms of dihydroisotanshinone I (DT), a compound in danshen (extract from danshen), on HNSCCs. Three HNSCCs cell lines were used for in vitro studies, and a Detroit 562 xenograft mouse model was chosen for in vivo studies. Our in vitro results showed that DT could initiate apoptosis, resulting in cell death, and the p38 signaling partially regulated DT-initiated cell apoptosis in the Detroit 562 model. In the xenograft mouse model, DT reduced tumor size with no obvious adverse effect of hepatotoxicity. The present study suggests that DT is a promising novel candidate for anti-HNSCCs therapy.

Dihydroisotanshinone I induced ferroptosis and apoptosis of lung cancer cells.

Danshen (Salvia miltiorrhiza Bunge) is broadly utilized in traditional Chinese medicine for lung cancer. However, it's exact effort and mechanism on lung cancer is fully unclear. In this study, we found that dihydroisotanshinone I (DT), a pure compound extracted from danshen, can inhibit the growth of A549 cells and H460 cells. DT also induced apoptosis and ferroptosis in these lung cancer cells. DT also blocking the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment can inhibit metastasis of A549 cells in the nude mice model without adverse effects on mice. In conclusion, DT inhibited the growth of lung cancer cells through apoptosis and ferroptosis and inhibited metastasis of A549 cells in the nude mice model. Further studies are warranted to validate the findings of this study.

Patients with comorbid rheumatoid arthritis are predisposed to peritonsillar abscess: real-world evidence.

PURPOSE: The peritonsillar abscess (PTA)-rheumatoid arthritis (RA) association remains unclear. Here, the effects of RA on PTA incidence and prognosis are elucidated. METHODS: We compared PTA incidence and prognosis of 30,706 RFCIP-registered patients with RA (RA cohort) with matched individuals without RA from another database of 1 million randomly selected people representing Taiwan's population (non-RA cohort). RESULTS: The RA cohort had significantly higher PTA incidence [incidence rate ratio (IRR) (95% CI) 1.73 (1.10-2.71), P = 0.017) and cumulative incidence (P = 0.016, Kaplan-Meier curves). Cox regression analyses demonstrated RA cohort to have an estimated 1.72-fold increased PTA risk (95% CI 1.09-2.69, P = 0.019). PTA was more likely within the first 5 years of RA diagnosis (for < 1, 1-5, and ≥ 5 postdiagnosis years, IRRs: 2.67, 2.31, and 1.10, respectively, and P = 0.063, 0.021, and 0.794, respectively; average onset duration: 4.3 ± 3.3 years after RA diagnosis). PTA increased length of hospital stay significantly and risk of complication with deep neck infection nonsignificantly [6.5 ± 4.5 vs 4.6 ± 2.8 days (P = 0.045) and 18.52% vs 7.81% (P = 0.155), respectively]. Moreover, RA-cohort patients not receiving RA therapy exhibited 5.06-fold higher PTA risk than those receiving RA-related therapy (95% CI 1.75-14.62, P = 0.003). CONCLUSIONS: In patients with RA, PTA incidence is the highest within 5 years of RA diagnosis, and RA therapy is essential for reducing PTA risk. LEVEL OF EVIDENCE: 4.

Traditional Chinese Medicine Enhances Survival in Patients with Gastric Cancer after Surgery and Adjuvant Chemotherapy in Taiwan: A Nationwide Matched Cohort Study.

BACKGROUND: Gastric cancer remains a major cancer globally. More than half of patients with gastric cancer undergo surgery in Taiwan; however, few large nationwide studies have investigated the effects of traditional Chinese medicine (TCM) on gastric cancer management after surgery. This study aimed to evaluate the effect of TCM on patients with gastric cancer following surgery and adjuvant chemotherapy in Taiwan and its prescription trends. METHODS AND MATERIALS: The cohort sampling data set was obtained from the Registry of Catastrophic Illness Patient Database, a research database of patients with severe illnesses from the National Health Insurance Research Database, Taiwan. Patients who had received a new diagnosis of gastric cancer and had undergone surgery were enrolled. We matched TCM users and nonusers at a ratio of 1 : 3 based on the propensity score, and TCM users were also grouped into short-term and long-term users. RESULTS: The number of TCM users and nonusers was 1701 and 5103 after applying the propensity score at a ratio of 1 : 3. Short-term users and long-term TCM users were independently associated with a decreased risk of death with HRs of 0.59 (95% confidence interval (CI), 0.55-0.65) and 0.41 (95% CI, 0.36-0.47), respectively, compared with TCM nonusers. We also obtained similar results when we adjusted for covariates in the main model, as well as each of the additional listed covariates. We also observed similar HR trends in short-term users and long-term TCM users among men and women aged <65 years and ≥65 years. The most commonly prescribed single herb and herbal formula in our cohort were Hwang-Chyi (Radix Hedysari; 11.8%) and Xiang-Sha-Liu-Jun-Zi-Tang (15.5%), respectively. CONCLUSION: TCM use was associated with higher survival in patients with gastric cancer after surgery and adjuvant chemotherapy. TCM could be used as a complementary and alternative therapy in patients with gastric cancer after surgery and adjuvant chemotherapy.

GB-2 inhibits ACE2 and TMPRSS2 expression: In vivo and in vitro studies.

After the first case of Coronavirus disease 2019 (COVID-19) was reported in Wuhan, COVID-19 has rapidly spread to almost all parts of world. Angiotensin converting enzyme 2 (ACE2) receptor can bind to spike protein of SARS-CoV-2. Then, the spike protein of SARS-CoV-2 can be cleaved and activated by transmembrane protease, serine 2 (TMPRSS2) of the host cells for SARS-CoV-2 infection. Therefore, ACE2 and TMPRSS2 are potential antiviral targets for treatment of prevention of SARS-CoV-2 infection. In this study, we discovered that 10-250 µg/mL of GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit ACE2 mRNA expression and ACE2 and TMPRSS2 protein expression in HepG2 and 293 T cells without cytotoxicity. GB-2 treatment could decrease ACE2 and TMPRSS2 expression level of lung tissue and kidney tissue without adverse effects, including nephrotoxicity and hepatotoxicity, in animal model. In the compositions of GB-2, we discovered that 50 µg/mL of theaflavin could inhibit protein expression of ACE2 and TMPRSS2. Theaflavin could inhibit the mRNA expression of ACE2. In conclusion, our results suggest that GB-2 and theaflavin could act as potential compounds for ACE2 and TMPRSS2 inhibitors in the further clinical study.

Maximum and Minimum Phonatory Glottal Area before and after Treatment for Vocal Nodules.

Background: Vocal fold nodules (VFNs) are a challenge for otolaryngologists. Glottal area (GA) waveform analysis is an examination method used for assessing vocal fold vibration and function. However, GA in patients with VFNs has rarely been studied. This study investigated the maximum and minimum GA in VFN patients using modern waveform analysis combining ImageJ software and videostroboscopy. Methods: This study enrolled 42 patients newly diagnosed with VFN, 15 of whom received voice therapy and 27 of whom underwent surgery. Acoustic parameters and maximum phonation time (MPT) were recorded, and patients completed the Chinese Voice Handicap Index-10 (VHI-C10) before and after treatment. After videostroboscopy examination, the maximum and minimum GAs were calculated using ImageJ software. The GAs of patients with VFNs before and after surgery or voice therapy were analyzed. Results: The MPTs of the patients before and after voice therapy or surgery did not change significantly. VHI-C10 scores decreased after voice therapy but the decrease was nonsignificant (14.0 ± 8.44 vs. 9.40 ± 10.24, p = 0.222); VHI-C10 scores were significantly decreased after surgery (22.53 ± 7.17 vs. 12.75 ± 9.84, p = 0.038). Voice therapy significantly increased the maximum GA (5.58 ± 2.41 vs. 8.65 ± 3.17, p = 0.012) and nonsignificantly decreased the minimum GA (0.60 ± 0.73 vs. 0.21 ± 0.46, p = 0.098). Surgery nonsignificantly increased the maximum GA (6.34 ± 3.82 vs. 8.73 ± 5.57, p = 0.118) and significantly decreased the minimum GA (0.30 ± 0.59 vs. 0.00 ± 0.00, p = 0.036). Conclusion: This study investigated the GA of patients with VFNs who received voice therapy or surgery. The findings indicated that voice therapy significantly increased maximum GA and surgery significantly decreased minimum GA. GA analysis could be applied to evaluate the efficacy of voice therapy, and it may help physicians to develop precise treatment for VFN patients (either by optimizing voice therapy or by performing surgery directly).

Author Correction: A hypoxia-responsive TRAF6-ATM-H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Danshen Improves Survival of Patients With Breast Cancer and Dihydroisotanshinone I Induces Ferroptosis and Apoptosis of Breast Cancer Cells.

Danshen (salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it is definite clinical effort and mechanism on breast cancer is unclear. In our study, we used the real-world database to investigate in vivo protective effort of danshen in the breast cancer patients through using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). In vitro, human breast cancer cells (MCF-7 cells and MDA-MB-231 cells) were used to investigate the effect and the underlying mechanism through XTT assay, flow cytometry, glutathione peroxidase (GPX) activity assay, GSH (reduced glutathione)/GSSG (oxidized glutathione), malondialdehyde (MDA), and western blot analysis. The in vivo effect was investigated through a xenograft nude mouse model. We found that dihydroisotanshinone I (DT), a pure compound present in danshen, can inhibit the growth of breast carcinoma cells, including MCF-7 cells and MDA-MB-231 cells. Moreover, DT induced apoptosis and ferroptosis in these breast cancer cells. DT also repressed the protein expression of GPX4 (Glutathione peroxidase 4). For in vivo study, DT treatment also significantly inhibited the final tumor volume without adverse effects in a xenograft nude mouse model. In conclusion, danshen has protective efforts in breast cancer patients, which could be attributed to DT through inducing apoptosis and ferroptosis of breast cancer cells.

Real-World Database Examining the Association between Sjögren's Syndrome and Chronic Rhinosinusitis.

OBJECTIVE: To investigate the risk of chronic rhinosinusitis (CRS) among patients with Sjögren's syndrome (SS). METHOD: A total of 18,723 patients diagnosed with SS between 1997 and 2011 were retrospectively analyzed. Moreover, 59,568 patients without SS were matched to patients with SS at a 1:4 ratio on the basis of sex, age, urbanization level, income level, and the comorbidities of rhinitis and nasal sepal deviation. Patients were followed up until death or the end of the study period (31 December, 2013). The primary outcome was the occurrence of CRS. RESULTS: The cumulative incidence of CRS was significantly higher in patients with SS than in those without SS (p < 0.001). The adjusted Cox proportional hazard model showed that patients with SS had a significantly higher incidence of CRS (hazard ratio, 2.51; 95% confidence interval, 2.22⁻2.84; p < 0.001). Sensitivity and subgroup analyses demonstrated SS was an independent risk factor for CRS. The dosage of intranasal corticosteroid spray used was not different between the SS and non-SS groups. Fewer patients with CRS in the SS group underwent sinus surgery (82/407 (20.2%)) than those in the non-SS group (179/667 (26.8%)) and this finding was statistically significant (p = 0.013). The number of operations did not differ significantly between patients with CRS in the SS and non-SS groups. CONCLUSIONS: SS is an independent risk factor for CRS. Our study extends the disease spectrum and prompts physicians to be aware of potential CRS occurrence after SS.

NVP-BEZ235 Attenuated Cell Proliferation and Migration in the Squamous Cell Carcinoma of Oral Cavities and p70S6K Inhibition Mimics its Effect.

NVP-BEZ235 or BEZ235 is a dual inhibitor of adenosine triphosphate (ATP)-competitive phosphoinositide 3-kinase (PI3K)/mammalian-target-of-rapamycin (mTOR) and is promising for cancer treatment. Because it targets more than one downstream effector, a dual approach is promising for cancer treatment. The aim of this study was to evaluate the efficacy of NVP-BEZ235 in treating oral cavity squamous cell carcinoma (OSCC). Two human OSCC cell lines, SCC-4 and SCC-25, were used in this study. PI3K-AKT signaling, proliferation, and cell migratory and invasion capabilities of OSCC cells were examined. In NVP-BEZ235-treated SCC-4 and SCC-25 cells, the phosphorylation of 70-kDa ribosomal S6 kinase (p70S6K), but not mTOR, decreased within 24 h. NVP-BEZ235 inhibited OSCC-cell proliferation, migration, and invasion possibly by directly deregulating the phosphorylation of p70S6K. The phospho-p70S6K inhibitor mimicked the effects of NVP-BEZ235 for preventing proliferation and weakening the migratory and invasion abilities of SCC-4 and SCC-25 cells. This study further confirmed the effect of NVP-BEZ235 on OSCC cells and provided a new strategy for controlling the proliferation, migration, and invasion of OSCC cells using the phopho-p70S6K inhibitor.

Antrodia cinnamomea extract inhibits the proliferation of tamoxifen-resistant breast cancer cells through apoptosis and skp2/microRNAs pathway.

BACKGROUND: Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. METHODS: Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western's blotting assay. RESULTS: Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10- 6 M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. CONCLUSIONS: These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

Dihydroisotanshinone I combined with radiation inhibits the migration ability of prostate cancer cells through DNA damage and CCL2 pathway.

BACKGROUND: Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 µM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. METHODS: DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western's blotting assay. RESULTS: The results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells. CONCLUSIONS: DT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.