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Introduction: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods: We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results: The median OS in this cohort was 14.2 months (95% CI, 12–16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4–0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54–0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005–1.554). Comparison between low (n = 464 patients) and high (n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection (p = 0.0001), higher Child-Pugh score (CPS) (p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score (p = 0.0015). Conclusion: Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Abstract Lung cancer remains the leading cause of cancer mortality, despite declining smoking rates. Previous lung cancer GWAS have identified numerous loci, but separating the genetic risks of lung cancer and smoking behavioral susceptibility remains challenging. Here, we perform multi-ancestry GWAS meta-analyses of lung cancer using the Million Veteran Program cohort (approximately 95% male cases) and a previous study of European-ancestry individuals, jointly comprising 42,102 cases and 181,270 controls, followed by replication in an independent cohort of 19,404 cases and 17,378 controls. We then carry out conditional meta-analyses on cigarettes per day and identify two novel, replicated loci, including the 19p13.11 pleiotropic cancer locus in squamous cell lung carcinoma. Overall, we report twelve novel risk loci for overall lung cancer, lung adenocarcinoma, and squamous cell lung carcinoma, nine of which are externally replicated. Finally, we perform PheWAS on polygenic risk scores for lung cancer, with and without conditioning on smoking. The unconditioned lung cancer polygenic risk score is associated with smoking status in controls, illustrating a reduced predictive utility in non-smokers. Additionally, our polygenic risk score demonstrates smoking-independent pleiotropy of lung cancer risk across neoplasms and metabolic traits.

Abstract Sickle cell anemia (SCA) negatively impacts the ability to achieve educational and occupational goals increasing vulnerability to socioeconomic challenges. In a cross‐sectional analysis of 332 SCA adults, we investigated whether the distressed community index (DCI) was associated with SCA‐related complications and nutritional status. More patients with higher DCI had Medicaid insurance. A higher DCI was independently associated with tobacco use and lower body mass index, serum albumin, and vitamin D 25‐OH levels after adjusting for insurance status but was not associated with SCA‐related complications. Future studies investigating access to healthy foods may help improve health equity in patients with SCA.

Background Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas.Methods We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR molecules containing various hinge, transmembrane, and co-stimulatory domains. These were lentivirally transduced into primary T cells and tested for antitumor activity in in vitro and in vivo B-cell lymphoma models.Results We found that the novel anti-CD79b monoclonal antibody was highly specific and bound only to human CD79b and no other cell surface protein. In testing the various CD79b-targeting CAR molecules, superior antitumor efficacy in vitro and in vivo was found for a CAR consisting CD8α hinge and transmembrane domains, an OX40 co-stimulatory domain, and a CD3ζ signaling domain. This CD79b CAR specifically recognized human CD79b-expressing lymphoma cell lines but not CD79b knock-out cell lines. CD79b CAR T cells, generated from T cells from either healthy donors or patients with lymphoma, proliferated, produced cytokines, degranulated, and exhibited robust cytotoxic activity in vitro against CD19+ and CD19– lymphoma cell lines and patient-derived lymphoma tumors relapsing after prior CD19 CAR T-cell therapy. Furthermore, CD79b CAR T cells were highly efficient at eradicating pre-established lymphoma tumors in vivo in three aggressive lymphoma xenograft models, including two cell line-derived xenografts and one patient-derived xenograft. Notably, these CAR T cells did not demonstrate any significant tonic signaling activity or markers of exhaustion.Conclusion Our results indicated that this novel CD79b CAR T-cell therapy product has robust antitumor activity against B-cell lymphomas. These results supported initiation of a phase 1 clinical trial to evaluate this product in patients with relapsed or refractory B-cell lymphomas.

Complications occurring after lymphodepleting chemotherapy (LDC) may delay chimeric antigen receptor (CAR) T-cell infusion. The effect of these delays on clinical outcomes is unclear. We performed a retrospective analysis of 240 patients with relapsed/refractory large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel (axi-cel) and identified 40 patients (16.7%) who had delay in axi-cel infusion. Of these, 85% had delay due to infection. At time of LDC initiation, patients with delayed infusion had lower absolute neutrophil count (P=0.006), lower platelets (P=0.004), lower hemoglobin (P5 days (4.6 vs. 8.2 months; P=0.036), but not 1 day (5.7 vs. 8.2 months; P=0.238). Following propensity score matching, patients with delayed infusion continued to have shorter median PFS (3.5 vs. 6.0 months; P=0.015). Levels of pro-inflammatory cytokines on day of infusion were significantly higher in patients with delayed infusion. Together, these findings suggest that delays in CAR T-cell administration after initiation of LDC are associated with inferior outcomes. Further studies are needed to guide strategies to improve efficacy in such patients.

Abstract Background Survivors of childhood cancer are at risk for therapy-related dental diseases. The purpose of the study was to investigate the associations between clinical, socioeconomic, and demographic factors and oral diseases in the St. Jude Lifetime Cohort (SJLIFE) participants. Methods We performed a retrospective medical chart review and evaluated longitudinal self-reported dental outcomes in 4856 childhood cancer survivors and 591 community controls participating in the St. Jude Lifetime Cohort (SJLIFE) study. Univariate and multivariable logistic regression models were used to assess the impact of socioeconomic factors, treatment exposures and patient demographics on dental outcomes. Results Cancer survivors were more likely to report microdontia (odds ratio (OR) = 7.89, 95% confidence interval (CI) [4.64, 14.90]), abnormal root development (OR = 6.19, CI [3.38, 13.00]), hypodontia (OR = 2.75, CI [1.83, 4.33]), enamel hypoplasia (OR = 4.24, CI [2.9, 6.49]), xerostomia (OR = 7.72, CI [3.27, 25.10]), severe gingivitis (OR = 2.04, CI [1.43, 3.03]), and ≥ 6 missing teeth (OR = 3.73, CI [2.46, 6.00]) compared to controls without cancer history. Survivors who received classic alkylating agents (OR = 1.6, CI [1.36, 1.88]), anthracycline antibiotics (OR = 1.22, CI [1.04, 1.42] or radiation therapy potentially exposing the oral cavity (OR = 1.48, CI [1.26, 1.72]) were more likely to report at least one dental health problem after controlling for socioeconomic factors, age at last follow-up and diagnosis, other treatment exposures, and access to dental services. Survivors who had radiation therapy potentially exposing the oral cavity (OR = 1.52, CI [1.25, 1.84]) were also more likely to report at least one soft tissue abnormality after controlling for socioeconomic factors, age at last follow-up and diagnosis, other treatment exposures, and access and utilization of dental services. Conclusions Childhood cancer survivors have a higher prevalence of oral-dental abnormalities than the controls without a cancer history. Cancer treatment, socioeconomic factors, and access to oral health care contribute to the prevalence of dental abnormalities.

The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.

Abstract Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed in 2013 to 2015 (28.8 months), and 2016 to 2019 (32.4 months). Likewise, 5-year survival rate has increased from 15.7% for patients diagnosed from 2004 to 2006 to 26% for those diagnosed from 2013 to 2015. Notably, survival improved for patients with BRAF V600E mutant as well as microsatellite unstable (MSI-H) tumors. Multivariate regression analysis identified surgical resection of liver metastasis (HR = 0.26, 95% CI, 0.19–0.37), use of immunotherapy (HR = 0.44, 95% CI, 0.29–0.67) and use of third line chemotherapy (regorafenib or trifluridine/tipiracil, HR = 0.74, 95% CI, 0.58–0.95), but not year of diagnosis (HR = 0.99, 95% CI, 0.98–1), as associated with better survival, suggesting that increased use of these therapies are the drivers of the observed improvement in survival.

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of HPK1, we showed that HPK1 inhibited Ras activity and its downstream signaling and regulated acinar cell plasticity. M46 promoted the development of ADM and PanINs. Expression of M46 in KrasG12D Bac mice promoted the infiltration of myeloid-derived suppressor cells and macrophages, inhibited the infiltration of T cells, and accelerated the progression of PanINs to invasive and metastatic PDAC, while HPK1 attenuated mutant Kras–driven PanIN progression. Our results showed that HPK1 plays an important role in ADM and the progression of PanINs by regulating Ras signaling. Loss of HPK1 kinase activity promotes an immunosuppressive tumor microenvironment and accelerates the progression of PanINs to PDAC.

The molecular mechanisms of resistance to immune checkpoint therapy remain elusive. Here, the authors perform immunogenomic analysis of TCGA data and data from clinical trials for antiPD-1/PD-L1 therapy and highlight the association of 9p21 loss with a cold tumor microenvironment and resistance to therapy.

Introduction: For maximum utility of molecular characterization by next-generation sequencing (NGS) and better understanding of tumor microenvironment with immune correlates analysis, biopsy specimens must yield adequate tumor tissue, and sequential biopsy specimens should sample a consistent site. We developed a web-based lesion selection tool (LST) that enables management and tracking of the biopsy specimen collections. Methods: Of 145 patients, the LST was used for 88 patients; the other 57 served as controls. We evaluated consistency of the lesion biopsied in longitudinal collections, number of cores obtained, and cores with adequate tumor cellularity for NGS. The Fisher exact test and Wilcoxon rank sum test were used to identify differences between the groups. Results: The analysis included 30 of 88 (34%) patients in the LST group and 52 of 57 (91%) in the control group. The LST workflow ensured 100% consistency in the lesions biopsied compared with 75% in the control group in longitudinal collections and increased the proportion of patients in whom at least five cores were collected per biopsy. Conclusions: The novel LST platform facilitates coordination, performance, and management of longitudinal biopsy specimens. Use of the LST enables sampling of the designated lesion consistently, which is likely to accurately inform us the effect of the treatment on tumor microenvironment and evolution of resistant pathways. Such studies are important translational component of any clinical trials and research as they guide the development of next line of therapy, which has significant effect on clinical utility. However, validation of this approach in a larger study is warranted.

Abstract The development of brain metastases (BMs) in breast cancer (BC) patients remains a challenging complication. Current clinical practice guidelines recommend local treatment of BMs without changing systemic therapy (CST) in patients with stable extracranial disease. We retrospectively investigated the impact of CST (when applicable as per treating physician’s discretion) following the diagnosis and management of oligometastatic (1–3) BMs in patients without extracranial metastases on the progression-free survival time (PFS), and overall survival (OS). Hazard ratios (HRs) were calculated using the Cox proportional hazard model. Among the 2645 patients with BC and BMs treated between 2002 and 2015, 74 were included for analysis. 40.5% of patients had HER2 + disease. Median time from diagnosis of BC to BMs was 17.6 months. 54%, 8%, and 38% of BMs were managed by radiation, craniotomy, or combination, respectively. Following the primary management of BMs, we observed that CST occurred in 26 (35.5%) patients, consisting of initiation of therapy in 13.5% and switching of ongoing adjuvant therapy in 22%. Median PFS was 6.6 months among patients who had CST compared to 7.1 months in those who did not (HR = 0.88 [0.52–1.47], p = 0.62). Median OS was 20.1 months among patients who had CST compared to 15.1 months in those who did not (HR = 0.68 [0.40–1.16], p = 0.16). Upon the successful local management of oligometastatic BMs in patients without extracranial disease, we did not find a significant difference in survival between patients who experienced a change in systemic therapy as compared to those who did not.

Objective: To compare the clinical efficacy and urodynamic parameter changes between the MiniArc and the Solyx sling for the treatment of female urodynamic stress incontinence (USI).Materials and Methods: One-hundred and thirty (MiniArc n = 79, BS-Solyx n = 51) patients were included in this study. Cough stress test (ST), pad test (PT), Incontinence Impact short form Questionnaire (IIQ-7), Urogenital Distress Inventory six-item questionnaire (UDI-6), Sexual Questionnaire-Short Form (PIS-Q), and urodynamic parametric changes were assessed to determine objective and subjective outcomes following the procedure. Objective cure was defined as negative ST and PT

Abstract Arsenic (As) exposure adversely affects neurodevelopment in children. Accumulation of misfolded proteins in cells exposed to As leads to endoplasmic reticulum (ER) stress response, which, if not relieved, results in cell death. Despite the potential role of ER stress for As-induced neurotoxicity, the underlying mechanisms remain poorly understood. Here we aimed to investigate the roles of microRNA(miR)-124, a novel ER stress suppressor, in As-induced ER stress response and cytotoxicity in neural cells. We further aimed to link these in vitro findings to neurodevelopmental outcomes in children who were exposed to As. Using Quantitative RT-PCR and Cyquant assay, we showed that miR-124 protects against As-induced cytotoxicity in neural cells with concomitant suppression of As-induced ER stress. In addition, As-induced cytotoxicity was exacerbated in miR-124 knockout cells generated by CRISPR-based gene editing compared scramble control. Furthermore, we identified two miR-124 SNPs rs67543816 (p = 0.0003) and rs35418153 (p = 0.0004) that are significantly associated with a mental composite score calculated from the Bayley Scales of Infant Development III in Bangladesh children. Our study reveals As-induced ER stress as a crucial mechanism underlying the toxic effects of As on neural cell function and neurodevelopment and identifies miR-124 as a potential preventative and therapeutic target against detrimental effects of As exposure in children.

Objective: The alternations of mtDNA may play an important role in the molecular pathogenesis and process of Pelvic Organ Prolapse (POP) formation in both pre-menopausal and post-menopausal women. The aim of the present study is to analyze the association between the mitochondrial biogenesis gene and development of POP in the uterosacral ligaments (UL) of pre-menopausal women. Materials and methods: Seventy one pre-menopausal women, all below 52 years of age, were enrolled in this study. UL biopsies were obtained from uterine specimens taken from 33 women with POP (n = 33, study group) and 38 myoma patients without POP (n = 38, control group). Quantitative Real-Time PCR was performed to measure mitochondrial DNA (mtDNA) copy number and mtDNA4977. Western blotting and immunohistochemistry were used to assess the protein expression of PGC-1α, TFAM, NRF-1 and NRF-2. Statistical analysis was performed using SPSS statistical software and the Mann–Whitney U test, and the continuous variables were analyzed using the Student's t-test in demographic data. Results: There were no significant differences in the patient demographics between the two groups (p > 0.05). The mtDNA copy number in the UL of pre-menopausal patients with prolapse was significantly higher than that in the no prolapse group (p = 0.008). There were no significant differences between the mtDNA4977 of the POP and non-POP groups, but a significantly higher expression of PGC-1α in the POP group compared to the non-POP group (1.59 ± 1.30 v.s. 0.66 ± 0.53; p = 0.036). The expression of TFAM in the POP group was higher than in the non-POP group). There was no significant difference in the TFAM(p = 0.377), NRF-1 and NRF-2 expression between the POP and non-POP groups (p = 0.647; p = 0.682). Conclusions: Changes in the PGC-1α and mtDNA copy number may play a role in the development of Pelvic Organ Prolapse in pre-menopausal patients. Keywords: Pre-menopause, Pelvic organ prolapse(POP), Gene expression, Mitochondrial DNA (mtDNA), Molecular pathogenesis

Objective Small bowel adenocarcinoma (SBA) is a rare malignancy with limited evidence regarding outcomes after curative resection of localised disease. We aimed to evaluate presentation and prognostic factors affecting overall survival (OS), relapse-free survival (RFS) and recurrence of SBA.Methods Consecutive patients with completely resected localised SBA (1979–2019) were retrospectively reviewed for presentation, patient and tumour characteristics, perioperative treatment, recurrence, outcomes, and prognostic factors.Results Among 257 total patients, median age was 58 years. Primary location was in the duodenum, jejunum and ileum in 52%, 29%, and 19% of patients, respectively. Median OS was 57.5 months and median follow-up was 40 months. In multivariate analysis, lymph node involvement, lymphovascular invasion, histologic grade and race were independent predictors of RFS, while race, stage and histologic grade were independent predictors of OS. No significant difference in OS or RFS was seen when evaluating the role of perioperative treatment. Median time to diagnosis from first medical evaluation was 31 days and did not change over time. Overall recurrence rate was 56%. Recurrence rate was higher in ileal (77%), than duodenal (54%) and jejunal (65%) SBA (p=0.01). Recurrence presented most commonly as distant metastasis (71%). Proficient mismatch repair was associated with decreased risk of locoregional recurrence (LR) but increased risk of distant recurrence (DR) when compared with deficient mismatch repair (dMMR) in univariate analysis.Conclusions Despite advances in diagnostic modalities, this study did not show any improvement in earlier diagnosis of SBA over the course of the past three decades. The predominant pattern of disease recurrence was distant across all SBA locations, but dMMR status demonstrated a robust predilection for LR as opposed to DR. Perioperative treatment did not improve outcomes; however, a lower stage disease was seen in patients that received neoadjuvant therapy, suggesting further exploration of this approach.

Summary: CRISPR genome engineering has become a powerful tool to functionally investigate the complex mechanisms of immune system regulation. While decades of work have aimed to genetically reprogram innate immunity, the utility of current approaches is restricted by poor knockout efficiencies or limited specificity for mature cell lineages in vivo. Here, we describe an optimized strategy for non-viral CRISPR-Cas9 ribonucleoprotein (cRNP) genomic editing of mature primary mouse innate lymphocyte cells (ILCs) and myeloid lineage cells that results in an almost complete loss of single or double target gene expression from a single electroporation. Furthermore, we describe in vivo adoptive transfer mouse models that can be utilized to screen for gene function during viral infection using cRNP-edited naive natural killer (NK) cells and bone-marrow-derived conventional dendritic cell precursors (cDCPs). This resource will enhance target gene discovery and offer a specific and simplified approach to gene editing in the mouse innate immune system.

Abstract Background Neurodevelopment is a complex process involving both genetic and environmental factors. Prenatal exposure to lead (Pb) has been associated with lower performance on neurodevelopmental tests. Adverse neurodevelopmental outcomes are more frequent and/or more severe when toxic exposures interact with genetic susceptibility. Methods To explore possible loci associated with increased susceptibility to prenatal Pb exposure, we performed a genome-wide gene-environment interaction study (GWIS) in young children from Mexico (n = 390) and Bangladesh (n = 497). Prenatal Pb exposure was estimated by cord blood Pb concentration. Neurodevelopment was assessed using the Bayley Scales of Infant Development. Results We identified a locus on chromosome 8, containing UNC5D, and demonstrated evidence of its genome-wide significance with mental composite scores (rs9642758, p meta = 4.35 × 10−6). Within this locus, the joint effects of two independent single nucleotide polymorphisms (SNPs, rs9642758 and rs10503970) had a p-value of 4.38 × 10−9 for mental composite scores. Correlating GWIS results with in vitro transcriptomic profiles identified one common gene, SLC1A5, which is involved in synaptic function, neuronal development, and excitotoxicity. Further analysis revealed interconnected interactions that formed a large network of 52 genes enriched with oxidative stress genes and neurodevelopmental genes. Conclusions Our findings suggest that certain genetic polymorphisms within/near genes relevant to neurodevelopment might modify the toxic effects of Pb exposure via oxidative stress.

A common complementary strategy in Genome-Wide Association Studies (GWAS) is to perform Gene Set Analysis (GSA), which tests for the association between one phenotype of interest and an entire set of Single Nucleotide Polymorphisms (SNPs) residing in selected genes. While there exist many tools for performing GSA, popular methods often include a number of ad-hoc steps that are difficult to justify statistically, provide complicated interpretations based on permutation inference, and demonstrate poor operating characteristics. Additionally, the lack of gold standard gene set lists can produce misleading results and create difficulties in comparing analyses even across the same phenotype. We introduce the Generalized Berk-Jones (GBJ) statistic for GSA, a permutation-free parametric framework that offers asymptotic power guarantees in certain set-based testing settings. To adjust for confounding introduced by different gene set lists, we further develop a GBJ step-down inference technique that can discriminate between gene sets driven to significance by single genes and those demonstrating group-level effects. We compare GBJ to popular alternatives through simulation and re-analysis of summary statistics from a large breast cancer GWAS, and we show how GBJ can increase power by incorporating information from multiple signals in the same gene. In addition, we illustrate how breast cancer pathway analysis can be confounded by the frequency of FGFR2 in pathway lists. Our approach is further validated on two other datasets of summary statistics generated from GWAS of height and schizophrenia.

Objective: The study aimed to explore the changes in mitochondrial DNA (mtDNA) copy number, collagen, and matrix metalloproteinase (MMPs) expression with pelvic organ prolapse (POP) in the uterosacral ligaments of premenopausal women. Materials and methods: A group of 56 premenopausal women, all younger than 52 years of age, were enrolled in this study. Uterosacral ligament (UL) biopsies were obtained from uterine specimens taken from 22 women with POP (n = 22, study group) and 34 myoma patients without POP (n = 34, control group) during abdominal or vaginal hysterectomy. Quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemistry analysis were applied in the present study. Results: The rate of high body mass index (BMI) (> 24 kg/m2) women was significantly higher in the POP group (81.8% vs. 35.3%, p = 0.001 *), and the BMI of the POP women was higher than that of the nonPOP women (p = 0.029 *). The mtDNA copy number (p = 0.001 *), collagen III alpha 1 (COL3α1) expression (p = 0.025 *), and MMP2 expression (p = 0.047 *) were significantly higher in the POP group when compared with the nonPOP group. The high BMI women had a higher mtDNA copy number (p = 0.002 *), COL3α1 (p = 0.028 *) gene expressions compared with the standard BMI women. Conclusion: In the premenopausal state, higher BMI may be a stronger associate factor than vaginal birth for the development of POP. The higher mtDNA copy number, COL3α1, and MMP2 gene expressions are highly associated with POP in the UL of premenopausal women.

Objective: To ascertain whether low preoperational maximal urethral closure pressure (MUCP) affects the outcomes of single incision sling (SIS) procedures and changes MUCP values postsurgery. Material and methods: There were 112 (MUCP ≥ 40 cmH2O, n = 88; MUCP

Introduction: Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. Methods: We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. Results: The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low (n = 464 patients) and high (n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection (p = 0.0001), higher Child-Pugh score (CPS) (p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score (p = 0.0015). Conclusion: Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate. [ABSTRACT FROM AUTHOR]