Abstract Several life‐prolonging therapies for metastatic castration‐resistant prostate cancer (mCRPC) are available, including radium‐223 dichloride ( 223 Ra), which was approved based on phase 3 ...data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real‐world evidence for 223 Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223 Ra was prescribed as part of routine practice by investigators. Patients with prior 223 Ra treatment were excluded. The primary objective was to assess 223 Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223 Ra was first‐ or second‐line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5–6 223 Ra cycles was 68.8%; this proportion was greater with first‐line use (84.3%) than second‐ (65.7%) or third‐/fourth‐line use (64.1%). More chemotherapy‐naïve patients (61.9%) completed the 6‐cycle 223 Ra treatment than chemotherapy‐exposed patients (56.7%). Any‐grade treatment‐emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223 Ra‐related adverse events. Median OS was 15.7 months (95% confidence interval 12.13–19.51); patients receiving 5–6 223 Ra injections and earlier 223 Ra use had longer OS than those receiving fewer injections and later 223 Ra use. 223 Ra provides a well‐tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases.
Diabetes is a chronic metabolic disease characterized by improperly regulating proteins, carbohydrates, and lipids due to insulin deficiency or resistance. The increasing prevalence of diabetes poses ...a tremendous socioeconomic burden worldwide, resulting in the rise of many studies on Chinese herbal medicines to discover the most effective cure for diabetes. Sesame seeds are among these Chinese herbal medicines that were found to contain various pharmacological activities, including antioxidant and anti-inflammatory properties, lowering cholesterol, improving liver function, blood pressure and sugar lowering, regulating lipid synthesis, and anticancer activities. These medicinal benefits are attributed to sesamin, which is the main lignan found in sesame seeds and oil. In this study, Wistar rat models were induced with type 2 diabetes using streptozotocin (STZ) and nicotinamide, and the effect of sesamin on the changes in body weight, blood sugar level, glycosylated hemoglobin (HbA1c), insulin levels, and the states of the pancreas and liver of the rats were evaluated. The results indicate a reduced blood glucose level, HbA1c, TG, and ALT and AST enzymes after sesamin treatment, while increased insulin level, SOD, CAT, and GPx activities were also observed. These findings prove sesamin’s efficacy in ameliorating the symptoms of diabetes through its potent pharmacological activities.
is widely known as a medical plant with broad indigenous ethnomedicinal uses, including anti-inflammatory, and antioxidant. Despite being used for remedies and ethnomedicinal purposes, the benefits ...obtained from
still need to be fully utilized. The underwhelming studies on its pharmacological potential, bioactive compounds, and mechanism of action keep the pharmacological and new drug discovery progress of this plant slow. This study focuses on the incorporation of in silico analyses such as ADME prediction and molecular docking simulations on the bioactive compounds identified in the plant to assess their potential for antioxidant and anti-inflammatory applications. A comparison of the ADME properties and molecular docking scores showed that naringenin, pinocembrin, and eriodictyol had the most potential to act as inhibitors of the target proteins involved in inflammation and oxidation pathways against the positive controls.
Parkinson’s disease (PD) is one of the large-scale health issues detrimental to human quality of life, and current treatments are only focused on neuroprotection and easing symptoms. This study ...evaluated in silico binding activity and estimated the stability of major metabolites in the roots of R. palmatum (RP) with main protein targets in Parkinson’s disease and their ADMET properties. The major metabolites of RP were subjected to molecular docking and QSAR with α-synuclein, monoamine oxidase isoform B, catechol o-methyltransferase, and A2A adenosine receptor. From this, emodin had the greatest binding activity with Parkinson’s disease targets. The chemical stability of the selected compounds was estimated using density functional theory analyses. The docked compounds showed good stability for inhibitory action compared to dopamine and levodopa. According to their structure–activity relationship, aloe-emodin, chrysophanol, emodin, and rhein exhibited good inhibitory activity to specific targets. Finally, mediocre pharmacokinetic properties were observed due to unexceptional blood–brain barrier penetration and safety profile. It was revealed that the major metabolites of RP may have good neuroprotective activity as an additional hit for PD drug development. Also, an association between redox-mediating and activities with PD-relevant protein targets was observed, potentially opening discussion on electrochemical mechanisms with biological functions.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is not only a chronic urinary bladder pain syndrome but is also associated with multifactorial etiology. Our study aimed to test the hypothesis ...that IC/BPS is associated with subsequent increased risks of outpatient visits and hospitalizations. Using nationwide database, the diagnoses were based on the International Classification Codes (ICD-9-CM) (595.1) of at least three outpatient services during 2002–2008, (n = 27,990) and cystoscopic finding Hunner type and/or glomerulation with pre-audit criteria. All recruited cases monitored for subsequent outpatient visits and hospitalizations for 2 years, including all-cause and specialty-specific departments, were classified according to medical specialty and age group (<40, 40–60, ≥60 years of age). IC/BPS patients have more overall outpatient department (OPD) visits and an overall adjusted incidence rate ratio (IRR) of 1.64. As for specialty, IRRs were higher in psychiatry (2.75), Chinese medicine (2.01), and emergency medicine (2.00), besides urology and gynecology. The IRRs decreased as age advanced (2.01, 1.71, and 1.44, respectively), except for gynecology (2.42, 2.52, and 2.81). A similar phenomenon happens in hospitalization with IRR of 1.69. Due to claim data characteristics, whether ulcer type IC/BPS findings can be deductive to non-ulcer type remains inclusive. Current results indicate the impacts of healthcare burden in broad spectrum about IC/PBS patients. IC/BPS has been suggested to be associated with lower threshold of healthcare visits and some coexisting disease and is comprised of systemic dysregulation, and is beyond the scope of local bladder-urethra disease. Adequate recognition of associated or comorbid factors and possible recommendation or referral for IC/BPS patients can help provide better healthcare quality.
The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic ...sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E₂ (PGE₂) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.
Studies have shown a high risk of tumor development within a bladder diverticulum (BD). We were interested in the relationship between BD and the development of bladder cancer. Herein, we attempted ...to investigate whether there exists an association between documented BD and subsequent risk of bladder cancer.
We identified 10,662 hospitalized urology patients, including 2,134 documented BD patients (study cohort) and 8,528 non-BD subjects (comparison cohort) from Taiwan's National Health Insurance database. Only urology patients were enrolled in the study to minimize selection bias. The two cohorts were frequency-matched 1:4 by age, sex and index-year. Patients with less than one year of follow-up were excluded to avoid inverting cause and effect. Risks of developing bladder cancer were estimated using the Cox proportional hazard regression model.
There was an increased bladder cancer risk in the documented BD patients. The incidence of bladder cancer in documented BD patients was 2.60-fold higher than that in the comparison group, and the overall risk-factor-adjusted hazard ratio was 2.63 (95% CI, 1.74-3.97). Moreover, stratified analysis by sex also showed that documented BD patients were at higher risk of subsequent bladder cancer than the comparison cohort. The effect of BD on the risk of bladder cancer was higher in males than in females and was more profound in patients without comorbidities than in those with comorbidities.
In this population-based longitudinal study, urology patients with documented BD might have an elevated risk of subsequent bladder cancer. Based on the limitations of the retrospective study design, further studies are required.
Background
To evaluate the safety and outcomes of single-port laparoscopic totally extraperitoneal (SPLTEP) and conventional laparoscopic totally extraperitoneal (CLTEP) hernioplasty.
Methods
...Retrospectively, we collected patients who underwent a laparoscopic totally extraperitoneal approach. The inclusion criteria were as follows: (1) male patients aged >20 years, (2) untreated hernia, and (3) American Society of Anesthesiologists (ASA) score ≤3. The exclusion criteria included: (1) additional procedures received during surgery, (2) inguinoscrotal hernia, (3) ASA score >3, (4) previous lower abdominal surgery, (5) bleeding disorders, and (6) incarcerated, obstructed, strangulated, or recurrent inguinal hernias. Patients were classified into SPLTEP and CLTEP groups. The demographics, body mass index (BMI), ASA score, comorbidities, blood loss, operation time, postoperative length of stay (LOS)/complications, hernia recurrence, visual analog scale (VAS), and postoperative analgesic requirements were collected for analysis.
Results
A total of 246 patients were enrolled. There were 103 patients in the SPLTEP group and 143 patients in the CLTEP group. The mean age was 56.1 ± 16.2 years versus 57.9 ± 15.1 years. There were no significances in demographics, BMI, ASA score, comorbidities, blood loss, operation time, postoperative LOS/complications, and hernia recurrence. The SPLTEP group had a shorter postoperative LOS, lower VAS at 18 hours postoperation, and a reduced amount of 24-hour postoperative analgesics.
Conclusion
SPLTEP hernioplasty is as safe as the CLTEP procedure. In addition, the SPLTEP group had a shorter LOS and a lower VAS score and required less postoperative analgesics. Further studies may focus on long-term complications, hernia recurrence, and chronic pain in these 2 groups.
Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. ...COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker.
Purpose: This study is aimed at investigating antineoplastic efficacy of histone deacetylase inhibitor (HDACI) LBH589 on renal cell
carcinoma (RCC) and elucidating the novel molecular mechanisms ...involved in growth arrest and apoptosis by targeting the important
nonhistone molecules.
Experimental Design: We analyzed the growth-inhibitory effect of LBH589 on RCC by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
assay in vitro and antitumor efficacy by xenograft experiments in vivo . To verify the associated molecular mechanisms involved in LBH589-mediated cell death and cell cycle progression by Western
blotting and fluorescence-activated cell sorting analysis.
Results: HDACI LBH589 induced degradation of both Aurora A and B kinases through a proteasome-mediated pathway by targeting HDAC3
and HDAC6. The dual degradation of Aurora A and B kinases mediated by LBH589 resulted in inducing G 2 -M arrest and apoptosis of renal cancer cell lines and our results also showed that LBH589 potently inhibited renal cancer
cell growth in vitro and suppressed tumor formation in vivo . The Aurora A and B kinases and HDAC3 are overexpressed in the human RCC tumor tissues examined, which make them perfect
targets for HDACI LBH589 treatment.
Conclusions: Our in vitro and in vivo data showed that LBH589 has potent anticancer effect of renal cancer cells. LBH589 and other HDACI treatment resulted in
inducing G 2 -M arrest and apoptosis of renal cancer cells through degradation of Aurora A and B kinases by inhibition of HDAC3 and HDAC6.
The clinical efficacy of LBH589 in the treatment of patients with metastatic RCC, especially those with high Aurora kinase
and HDAC expression, is worthy of further investigation.
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