Patient-reported symptom burden and circulating cytokines undergoing chemotherapy: a pilot study in patients with ovarian cancer.

OBJECTIVE: To analyze the fluctuations of patient-reported outcomes (PROs) and their relationships with cytokines in the peripheral blood of patients undergoing chemotherapy for ovarian cancer (OC). METHODS: PROs burden was prospectively measured by the M.D. Anderson Symptom Inventory-Ovarian Cancer (MDASI-OC) at baseline before chemotherapy, on a daily basis during and post-chemotherapy days (PCD) 7, 14, and 20. Cytokines were collected at baseline, days prior to hospital discharge and PCD 20. Pearson correlation was used to explore the associations between PROs and cytokines levels in peripheral blood. RESULTS: The top 8 rated symptoms were compared between the neoadjuvant chemotherapy (NACT) group (n=20) and the postoperative adjuvant chemotherapy (PAC) group (n=7). Before chemotherapy, the mean scores of fatigue and lack of appetite in the NACT group were higher than those in the PAC group. After chemotherapy, pain, nausea, vomiting, disturbed sleep, lack of appetite, and constipation increased to peak during PCD 2-6; while, fatigue and numbness or tingling remained at high levels over PCD 2-13. By PCD 20, disturbed sleep and fatigue showed a significant increase in mean scores, particularly in the NACT group; while, other symptom scores decreased and returned to baseline levels. Additionally, the longitudinal fluctuations in pain, fatigue, and lack of appetite were positively associated with circulating levels of interleukin-6 and interferon gamma (p<0.05). CONCLUSION: MDASI-OC was feasible and adaptable for demonstrating the fluctuations of symptom burden throughout chemotherapy course. Moreover, symptoms changing along with cytokines levels could provide clues for exploring mechanism underlying biochemical etiology.

Magnetic resonance imaging-based Classifications for Symptom of Adenomyosis.

OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810～0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018～12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131～2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.

Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

Serum CA125 as a biomarker for dysmenorrhea in adenomyosis.

OBJECTIVE: To explore the association between CA125 and dysmenorrhea in adenomyosis, and the factors affecting CA125 in adenomyosis. METHODS: Patients were grouped a the presence of dysmenorrhea. The receiver operating characteristic (ROC) curve was applied to assess the utility of CA125 for dysmenorrhea. Binary logistic regression was employed to identify the factors associating dysmenorrhea and CA125 level. RESULTS: Patients in the dysmenorrhea group had higher CA125 levels than those in the non-dysmenorrhea group. For those with dysmenorrhea, CA125 levels of diffuse subtype group were higher than those of the focal subtype group. The CA125 level of 35 U/mL was validated as the optimal cut-point for dysmenorrhea in ROC curves. Compared with patients whose CA125 was 35 U/mL or less, those with CA125 levels greater than 35 U/mL were more likely to have dysmenorrhea. Thereafter, the multiple regression analysis showed that adenomyotic lesion volume was positively correlated with CA125 level in the total cohort and subtype groups, while age was negatively correlated with CA125 level in the total cohort and diffuse subtype. CONCLUSIONS: The pathogenesis of adenomyosis is not clear. CA125 was associated with dysmenorrhea in adenomyosis, and, furthermore, CA125 level is positively correlated with the severity of the disease.

Early return to work: Single-port vs. multiport laparoscopic surgery for benign ovarian tumor.

Objective: To compare the return to work (RTW) time between single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for benign ovarian tumors. Methods: A cross-sectional cohort study was conducted, which consisted of 335 women of reproductive age with benign ovarian tumors and who were keen on returning to work as early as possible. Surgical outcomes, postoperative pain score, postoperative satisfaction with the cosmesis score (CS), and the RTW time of the SPLS group were compared with those of the MPLS group. Besides, the RTW time and CS were calculated from the questionnaire survey by a single specialized gynecologist. Results: Women who met the inclusion criteria were included in the SPLS (n = 106) and MPLS groups (n = 229). The RTW time in the SPLS group (22.13 ± 27. 06 days) was significantly shorter than that in the MPLS group (46.08 ± 57.86 days) (P < 0.001). The multivariate Cox analysis results showed that age (HR = 0.984, 95% CI, 0.971-0.997, P = 0.020), SPLS (HR = 3.491, 95% CI, 2.422-5. 032, P < 0.001), and return to normal activity time (HR = 0.980, 95% CI, 0.961-0.998, P = 0.029) were independent factors of the RTW time. Conclusions: SPLS may be advantageous in terms of shortening the RTW time for women with benign ovarian tumors.

TANK-Binding Kinase 1 (TBK1) Serves as a Potential Target for Hepatocellular Carcinoma by Enhancing Tumor Immune Infiltration.

Background: Numerous cancer types present the aberrant TANK-binding kinase 1 (TBK1) expression, which plays an important role in driving inflammation and innate immunity. However, the prognostic role of TBK1 and its relationship with immune cell infiltration in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression and prognostic value of TBK1 was analyzed by Tumor Immune Estimation Resource (TIMER), Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and further confirmed in the present cohort of patients with HCC. The association between TBK1 and HCC immune infiltrates, and its potential mechanism were investigated via analyses of the Tumor Immune Estimation Resource, tumor-immune system interactions database (TISIDB), CIBERSORT, STRING, and Metascape. The effect of TBK1 on immune infiltrates and the therapeutic value of targeting TBK1 were further investigated in a HCC mouse model by treatment with a TBK1 antagonist. Results: The level of TBK1 expression in HCC was higher than that measured in normal tissues, and associated with poorer overall survival (GEPIA: hazard ratio [HR]=1.80, P=0.038; Kaplan-Meier plotter: HR=1.87, P<0.001; CPTAC: HR=2.23, P=0.007; Our cohort: HR=2.92, P=0.002). In addition, high TBK1 expression was found in HCC with advanced TNM stage and identified as an independent poor prognostic factor for overall survival among patients with HCC. In terms of immune infiltration, tumor tissues from HCC patients with high TBK1 expression had a low proportion of CD8+ T cells, and TBK1 expression did not show prognostic value in HCC patients with enriched CD8+ T cells. Furthermore, TBK1 expression was positively correlated with the markers of T cell exhaustion and immunosuppressive cells in the HCC microenvironment. Mechanistically, the promotion of HCC immunosuppression by TBK1 was involved in the regulation of inflammatory cytokines. In vivo experiments revealed that treatment with a TBK1 antagonist delayed HCC growth by increasing the number of tumor-infiltrating CD8+ T cells. Conclusions: The up-regulated expression of TBK1 may be useful in predicting poor prognosis of patients with HCC. In addition, TBK1, which promotes the HCC immunosuppressive microenvironment, may be a potential immunotherapeutic target for patients with HCC.

Hes1 is associated with long non-coding RNAs in colorectal cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) play important roles in the development and pathophysiology of colorectal cancer (CRC). Our previous study showed that Hes1 was involved in the self-renewal and tumorigenicity of stem-like cancer cells in CRC. METHODS: ArrayStar Human LncRNA/mRNA Expression Microarray Version 3.0 was used to detect lncRNA expression in CRC tissues compared with their matched non-tumoral tissues. RNA-binding protein immunoprecipitation and sequencing (RIP-seq) assay was used to detect lncRNAs binding to Hes1. Real-time qPCR was used to detect expression of specific lncRNAs in CRC tissues. RESULTS: We found significantly up-regulated as well as down-regulated lncRNAs in CRC tissues compared with their matched non-tumoral tissues. We also screened a number of lncRNAs interacting with Hes1 in CRC cells. Interestingly, we found several lncRNAs binding to Hes1 (such as, GNAS-AS1, RP11-89K10.1, and RP11-465L10.10) were up-regulated in CRC tissues showed by the tissue microarray. Next, we confirmed that Hes1 directly interacted with these lncRNAs using RIP-qPCR and RNA pulldown assay. Finally, we verified the expression of these lncRNAs in 32 CRC samples as well as the adjacent non-tumoral tissues using real-time qPCR. CONCLUSIONS: Based on these, we speculate that Hes1 interacts with one or more lncRNAs which contribute to the development and progression of CRC.

Apigenin potentiates the growth inhibitory effects by IKK-ß-mediated NF-κB activation in pancreatic cancer cells.

Apigenin is a potential chemopreventive agent for cancer prevention. Because of the central role of transcription factor nuclear factor-κB (NF-κB) in pancreatic cancer, we investigated the roles of NF-κB in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. Apigenin treatment down-regulated not only basal but also TNF-α-induced NF-κB DNA binding activity, NF-κB transcription activity, inhibitor of κB (IκB)-α phosphorylation together with translocation of p65 and p50, and it accompanied with the blockade of IκB kinase (IKK)-ß activity. Moreover, IKK blockage potentiated the anticancer efficacy of apigenin and IKK-ß overexpression attenuated the apigenin-induced cell growth inhibition. Additionally, apigenin (30 mg/kg) administration suppressed pancreatic cancer growth and IKK-ß activation in nude mice xenograft. These results indicated that apigenin had a potential to inhibit IKK-ß-mediated NF-κB activation, and was a valuable agent for the pancreatic cancer treatment.