PEITC Induces DNA Damage and Inhibits DNA Repair-Associated Proteins in Human Retinoblastoma Cells In Vitro.

Phenethyl isothiocyanate (PEITC), a natural product, exists in biological activities, including anticancer activity in many human cancer cells. No information shows that PEITC affects DNA damage in human retinoblastoma (RB) cells in vitro. In this study, the aim of experiments was to determine whether PEITC decreased total viable cell number or not by inducing protein expressions involved in DNA damage and repair in Y79 RB cells in vitro. Total cell viability was measured by PI exclusion assay, and PEITC reduced the total Y79 viable cell numbers in a dose-dependent manner. DNA condensation and DNA impairment were conducted by DAPI staining and comet assays, respectively, in Y79 cells. The findings show that PEITC induced DNA condensation dose-dependently based on the brighter fluorescence of cell nuclei stained by DAPI staining. PEITC-induced DNA damage showed a more extended DNA migration smears than that of the control, which was performed by a comet assay. Western blotting was performed to measure the protein expressions involved in DNA damage and repair, which showed that PEITC at 2.5-10 µM increased NRF2, HO-1, SOD (Mn), and catalase; however, it decreased SOD (Cu/Zn) except 10 µM PEITC treatment, and decreased glutathione, which were associated with oxidative stress. Furthermore, PEITC increased DNA-PK, MDC1, H2A.XpSer139, ATMpSer1981, p53, p53pSer15, PARP, HSP70, and HSP90, but decreased TOPIIα, TOPIIß, and MDM2pSer166 that were associated with DNA damage and repair mechanism in Y79 cells. The examination from confocal laser microscopy shows that PEITC increased H2A.XpSer139 and p53pSer15, and decreased glutathione and TOPIIα in Y79 cells. In conclusion, the cytotoxic effects of PEITC on reducing the number of viable cells may be due to the induction of DNA damage and the alteration of DNA repair proteins in Y79 cells in vitro.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Association between polyphenol subclasses and prostate cancer: a systematic review and meta-analysis of observational studies.

Background: The effect of polyphenol subclasses on prostate cancer (PCA) is controversial. Therefore, the purpose of this study was to investigate the relationship between polyphenol subclasses and PCA incidence. Methods: From the establishment of the database to December 2023, a systematic search was conducted on PubMed, Web of Science, Embase, and Cochrane Library to identify relevant observational studies. The adjusted odds ratio (OR) and corresponding 95% confidence interval (95% CI) were used to assess the association. Results: A total of 38 studies (11 were cohort studies and 27 were case-control studies), composing 824,933 participants, were included in this meta-analysis after excluding irrelevant records. The findings of the study revealed that men who consumed dietary polyphenols had a significantly higher risk of PCA compared to those who never or rarely consumed dietary polyphenols (OR = 1.01, p = 0.023), especially dietary flavonol (OR = 1.05, p = 0.042), flavanol (OR = 1.03, p = 0.026) and anthocyanin (OR = 1.06, p = 0.001). Neither total nor subclasses of dietary polyphenols have an effect on non-localized or high-grade PCA (OR = 1.01, p = 0.518). Dietary isoflavones tended to reduce the incidence of local or low-grade PCA, although there was no statistically significant difference (OR = 1.00, p = 0.081). Regarding serum/plasma polyphenol, total polyphenol (OR = 0.95, p = 0.002), genistein (OR = 0.92, p = 0.029) and enterolactone (OR = 0.92, p = 0.022) can reduce the incidence of PCA. No association was observed between total/subclasses of urinary polyphenols and PCA risk. Conclusion: Polyphenols seem to generally increase the risk of PCA in the male population. The effect of polyphenols on PCA is affected by factors such as polyphenol subclasses, their forms (serum/plasma, urinary, dietary), and PCA-related factors (like PCA stage). Systematic review registration: identifier: CRD42022322699.

Immunophenotypic Landscape of synovial tissue in rheumatoid arthritis: Insights from ACPA status.

Objective: To examine the clinical features and synovial pathologies in rheumatoid arthritis (RA) patients across varying titers of circulating anti-citrullinated protein antibodies (ACPA). Methodology: We devised a negative pressure suction and rebound synovial biopsy tool to enhance the yield of synovial biopsies, noted for its ease and safety of use. This research involved a retrospective examination of 60 active RA patients who underwent synovial biopsies with this tool from June to November 2013 at our institution. A range of disease activity markers were collected, including DAS28-CRP, ESR, CRP, count of swollen and tender joints, VAS pain scale, and so forth. Synovial tissue underwent HE staining and immunohistochemistry, including synovitis grading (GSS) and counting of B cells (CD20), T cells (CD3), macrophages (CD68), and plasma cells (CD138). Participants: were categorized into three groups as per ACPA titers: ACPA-negative (0-5U/mL), low-titer (5-20U/mL), and high-titer (above 20U/mL). The study compared the clinical features and synovial pathologies across these groups. Results: Of the 60 RA patients, they were segregated into three groups based on ACPA titers: 20 in ACPA-negative, 9 in the low-titer group, and 31 in the high-titer group. No significant differences were observed in GSS scores, synovial cell proliferation and loss, matrix activation, inflammatory infiltration, and neovascularization among these groups (P > 0.05). The high-titer ACPA group demonstrated significantly increased counts of CD3+ T cells, CD20+ B cells, and CD68+ macrophages in synovial tissues compared to the ACPA-negative and low-titer groups (p < 0.05), along with a higher incidence of ectopic lymphoid neogenesis (p < 0.05). Ordinal logistic regression revealed that rheumatoid factor (RF), and counts of synovial T cells, B cells, macrophages, and ectopic lymphoid neogenesis correlated with ACPA titers (P < 0.05), particularly lymphoid neogenesis (OR = 3.63, P = 0.023). Conclusion: RA patients with high-titer ACPA demonstrate elevated levels of inflammatory cell infiltration in synovial tissues, with ectopic lymphoid neogenesis showing a strong correlation with high ACPA positivity.

Nrf2 induces angiogenesis in spinal cystic echinococcosis by activating autophagy via regulating oxidative stress.

Spinal cystic echinococcosis (CE) is a rare but malignant zoonosis that can cause disability or even death in more than half of patients. Due to the complex pathological features, it is not curable by conventional drugs and surgery, so new therapeutic targets urgently need to be discovered. In this study, we clarify the occurrence of the phenomenon of spinal encapsulation angiogenesis and explore its underlying molecular mechanisms. A co-culture system was established by protoscoleces (PSCs) with human umbilical vein endothelial cells (HUVECs) which showed a high expression level of Nrf2. A short hairpin RNA (shRNA) and Sulforaphane (SFN) affecting the expression of Nrf2 were used to treat HUVECs. The results showed that Nrf2 could promote the tube formation of HUVECs. Nrf2 also exerts a protective effect against HUVECs, which is achieved by promoting NQO1 expression to stabilize ROS levels. Furthermore, autophagy activation significantly promotes angiogenesis in the spinal echinococcosis model (SEM) as a result of Nrf2 regulation of oxidative stress. These results suggest that the ROS/Nrf2/autophagy axis can induce angiogenesis and may be a potential target for the treatment of spinal cystic echinococcosis.

Efficacy of salvage surgery versus re-irradiation for isolated regional lymph node recurrence in patients with nasopharyngeal carcinoma.

BACKGROUND: To compare the clinical characteristics and prognoses of patients with isolated regional lymph node recurrent nasopharyngeal carcinoma (irrNPC) who underwent surgery or re-irradiation treatment. METHODS: We retrospectively reviewed 124 irrNPC patients who underwent initial radiotherapy between January 2010 and December 2020. The staging of regional lymph node recurrence was as follows: 75.8% for rN1, 14.5% for rN2, and 9.7% for rN3. Fifty-five patients underwent regional lymph node surgery (Surgery group), and sixty-nine patients received salvage radiotherapy with or without chemotherapy (Re-irradiation group). The survival rate was compared using Kaplan‒Meier analysis and evaluated by the log-rank test. Cox proportional hazard models were used to analyze prognostic factors. RESULTS: The median follow-up time was 70 months, the 5-year overall survival (OS) was 74%, and the median survival time was 60.8 months. There were no significant differences in 5-year OS (75.6% vs. 72.4%, P = 0.973), regional recurrence-free survival (RRFS, 62.7% vs. 71.1%, P = 0.330) or distant metastasis-free survival (DMFS, 4.2% vs.78.7%, P = 0.677) between the Surgery group and Re-irradiation group. Multivariate analysis revealed age at recurrence, radiologic extra-nodal extension (rENE) status, and recurrent lymph node (rN) classification as independent prognostic factors for OS. The rENE status was an independent prognostic factor for DMFS. Subgroup analysis of the Surgery group revealed that the rN3 classification was an adverse prognostic factor for OS. Age at recurrence ≥ 50 years, GTV-N dose, and induction chemotherapy were found to be independent prognostic factors for OS, RRFS, and DMFS, respectively, in the Re-irradiation group. CONCLUSIONS: For NPC patients with isolated regional lymph node recurrence after initial radiotherapy, those who underwent surgery had survival prognosis similar to those who underwent re-radiotherapy with or without chemotherapy. A prospective study is needed to validate these findings.

PW06 suppresses cancer cell metastasis in human pancreatic carcinoma MIA PaCa-2 cells via the inhibitions of p-Akt/mTOR/NF-κB and MMP2/MMP9 signaling pathways in vitro.

PW06 [(E)-3-(9-ethyl-9H-carbazol-3-yl)-1-(2,5-dimethoxyphenyl) prop-2-en-1-one], a kind of the carbazole derivative containing chalcone moiety, induced cell apoptosis in human pancreatic carcinoma in vitro. There is no investigation to show that PW06 inhibits cancer cell metastasis in human pancreatic carcinoma in vitro. Herein, PW06 (0.1-0.8 µM) significantly exists in the antimetastatic activities of human pancreatic carcinoma MIA PaCa-2 cells in vitro. Wound healing assay shows PW06 at 0.2 µM suppressed cell mobility by 7.45 and 16.55% at 6 and 24 hours of treatments. PW06 at 0.1 and 0.2 µM reduced cell mobility by 14.72 and 21.8% for 48 hours of treatment. Transwell chamber assay indicated PW06 (0.1-0.2 µM) suppressed the cell migration (decreased 26.67-35.42%) and invasion (decreased 48.51-68.66%). Atomic force microscopy assay shows PW06 (0.2 µM) significantly changed the shape of cell morphology. The gelatin zymography assay indicates PW06 decreased MMP2's and MMP9's activities at 48 hours of treatment. Western blotting assay further confirms PW06 reduced levels of MMP2 and MMP9 and increased protein expressions of EGFR, SOS1, and Ras. PW06 also increased the p-JNK, p-ERK, and p-p38. PW06 increased the expression of PI3K, PTEN, Akt, GSK3α/ß, and E-cadherin. Nevertheless, results also show PW06 decreased p-Akt, mTOR, NF-κB, p-GSK3ß, ß-catenin, Snail, N-cadherin, and vimentin in MIA PaCa-2 cells. The confocal laser microscopy examination shows PW06 increased E-cadherin but decreased vimentin in MIA PaCa-2 cells. Together, our findings strongly suggest that PW06 inhibited the p-Akt/mTOR/NF-κB/MMPs pathways, increased E-cadherin, and decreased N-cadherin/vimentin, suppressing the migration and invasion in MIA PaCa-2 cells in vitro.

Radiomics nomogram for predicting disease-free survival after partial resection or radical cystectomy in patients with bladder cancer.

OBJECTIVES: To create a MRI-derived radiomics nomogram that combined clinicopathological factors and radiomics signature (Rad-score) for predicting disease-free survival (DFS) in patients with bladder cancer (BCa) following partial resection (PR) or radical cystectomy (RC), including lymphadenectomy (LAE). METHODS: Finally, 80 patients with BCa after PR or RC with LAE were enrolled. Patients were randomly split into training (n = 56) and internal validation (n = 24) cohorts. Radiomic features were extracted from T2-weighted, dynamic contrast-enhanced, diffusion-weighted imaging, and apparent diffusion coefficient sequence. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was applied to choose the valuable features and construct the Rad-score. The DFS prediction model was built using the Cox proportional hazards model. The relationship between the Rad-score and DFS was assessed using Kaplan-Meier analysis. A radiomics nomogram that combined the Rad-score and clinicopathological factors was created for individualized DFS estimation. RESULTS: In both the training and validation cohorts, the Rad-score was positively correlated with DFS (P < .001). In the validation cohort, the radiomics nomogram combining the Rad-score, tumour pathologic stage (pT stage), and lymphovascular invasion (LVI) achieved better performance in DFS prediction (C-index, 0.807; 95% CI, 0.713-0.901) than either the clinicopathological (C-index, 0.654; 95% CI, 0.467-0.841) or Rad-score-only model (C-index, 0.770; 95% CI, 0.702-0.837). CONCLUSION: The Rad-score was an independent predictor of DFS for patients with BCa after PR or RC with LAE, and the radiomics nomogram that combined the Rad-score, pT stage, and LVI achieved better performance in individual DFS prediction. ADVANCES IN KNOWLEDGE: This study provided a non-invasive and simple method for personalized and accurate prediction of DFS in BCa patients after PR or RC.