Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

Prenatal exposure to low-dose di-(2-ethylhexyl) phthalate (DEHP) induces potentially hepatic lipid accumulation and fibrotic changes in rat offspring.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used to enhance the flexibility and durability of various products. As an endocrine disruptor, DEHP can interfere with normal hormonal functions, posing substantial health risks to organisms. Given the critical role of the liver in DEHP metabolism, we investigated potential liver damage in offspring induced by prenatal exposure to low doses of DEHP in Sprague Dawley rats. Pregnant rats were divided into three groups and administered 20 or 200 µg/kg/day of DEHP or corn oil vehicle control via oral gavage from gestation days 0-20. Male rat offspring were euthanized on postnatal day 84, and blood and liver specimens were collected for analysis. We observed fibrotic changes in the livers of the exposed groups, accompanied by the proliferation and activation of hepatic stellate cells and upregulated expression of TGF-B and collagen 1A1. Additionally, an inflammatory response, characterized by increased macrophage infiltration and elevated levels of pro-inflammatory cytokines, was evident. Third, hepatic and serum triglyceride and serum cholesterol were notably increased, along with upregulated expression of lipid metabolism-related proteins, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and diacylglycerol O-acyltransferase 1, particularly in the low-dose group. These results suggest that prenatal exposure to DEHP can disrupt lipid metabolism, resulting in hepatic lipid accumulation in the offspring. This exposure may also induce an inflammatory response that contributes to the development of liver fibrosis. Thus, even at relatively low doses, such exposure can precipitate latent liver damage in offspring.

Loss of ficolin-3 expression is associated with poor prognosis in patients with hepatocellular carcinoma.

Background: Ficolin-3 (FCN3) is a well-known circulating pattern recognition molecule which plays a role in host immune responses to cancer via activation of the lectin complement pathway. Nevertheless, the clinical significance of FCN3 in patients with hepatocellular carcinoma (HCC) is unclear. Methods: Eighty-seven HCC patients who received hepatectomy at our hospital were included. Immunohistochemical staining was used to assess the FCN3 expression in both tumorous and non-tumorous tissues from the patients, who were classified into high and low expression groups. Differences in clinicopathological characteristics between the two groups were then analyzed. Results: Survival was significantly associated with FCN3 immunohistochemical score (p for trend = 0.048). Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high FCN3 expression than in those with a low FCN3 expression (p=0.031). A high FCN3 expression in tumor tissue was independently associated with better overall survival (p=0.042). However, multivariate analysis showed that FCN3 expression was not an independent risk factor for overall survival. Conclusion: Our findings suggest that FCN3 is significantly related to the prognosis of HCC. FCN3 may be a prognostic marker in patients with HCC.

Elevated plasma leptin levels are associated with vascular access dysfunction in patients on maintenance hemodialysis.

BACKGROUND: Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO). METHODS: A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin. RESULTS: The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin. CONCLUSIONS: In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.

Plasma levels and tissue expression of liver-type fatty acid-binding protein in patients with breast cancer.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) is widely expressed in hepatocytes and plays a role in lipid metabolism. It has been demonstrated to be overexpressed in different types of cancer; however, few studies have investigated the association between L-FABP and breast cancer. The aim of this study was to assess the association between plasma concentrations of L-FABP in breast cancer patients and the expression of L-FABP in breast cancer tissue. METHOD: A total of 196 patients with breast cancer and 57 age-matched control subjects were studied. Plasma L-FABP concentrations were measured using ELISA in both groups. The expression of L-FABP in breast cancer tissue was examined using immunohistochemistry. RESULT: The patients had higher plasma L-FABP levels than the controls (7.6 ng/mL (interquartile range 5.2-12.1) vs. 6.3 ng/mL (interquartile range 5.3-8.5), p = 0.008). Multiple logistic regression analysis showed an independent association between L-FABP and breast cancer, even after adjusting for known biomarkers. Moreover, the rates of pathologic stage T2+T3+T4, clinical stage III, positive HER-2 receptor status, and negative estrogen receptor status were significantly higher in the patients with an L-FABP level greater than the median. Furthermore, the L-FABP level gradually increased with the increasing stage. In addition, L-FABP was detected in the cytoplasm, nuclear, or both cytoplasm and nuclear of all breast cancer tissue examined, not in the normal tissue. CONCLUSIONS: Plasma L-FABP levels were significantly higher in the patients with breast cancer than in the controls. In addition, L-FABP was expressed in breast cancer tissue, which suggests that L-FABP may be involved in the pathogenesis of breast cancer.

Chemical Stability and Transformation of Molybdenum Disulfide Nanosheets in Environmental Media.

Layered transition metal dichalcogenides, including molybdenum disulfide (MoS2), have previously been considered stable in the ambient environment due to the absence of dangling bonds in the electron-filled shells of the end chalcogen atoms. Here, we evaluate the chemical stability of MoS2 nanosheets fabricated by chemical exfoliation (ceMoS2) and surfactant dispersion (sMoS2). The results demonstrate that sMoS2 exhibits greater long-term persistence. Contrarily, ceMoS2 underwent progressive deterioration, in which preferential oxidation of the 1T of a mixture of 1T and 2H phases was observed. The oxidative degradation of ceMoS2 was retarded in the presence of natural organic matter (NOM), including Suwannee River natural organic matter (SRNOM) and Aldrich humic acid (ALHA), in the dark ambient condition, while the aging process of MoS2 with co-occurring ALHA was accelerated under sunlight exposure. The observed inhibition effect on the deterioration of ceMoS2 by NOM was mainly attributed to slower dissolution kinetics with rapid initial oxidation (i.e., forming Mo-O bonding) or carbon grafting, rather than prevention of the formation of secondary small suspended Mo-containing particles. The compiled results highlight that the environmental fate of MoS2 nanosheets will be regulated by the combined effects of exfoliating agents and environmentally relevant factors including organic macromolecules and sunlight exposure.

Monocytic thrombomodulin promotes cell adhesion through interacting with its ligand, Lewisy.

The leukocyte adhesion cascade involves multiple events that efficiently localize circulating leukocytes into the injured sites to mediate inflammatory responses. From rolling to firm adhesion, the interactions between adhesion molecules have pivotal roles in increasing the avidity of leukocytes to endothelial cells. Thrombomodulin (TM), an essential anticoagulant protein in the vasculature, is also expressed on leukocytes. We previously demonstrated that Lewisy (Ley), a specific ligand of TM, is upregulated in inflamed endothelium and is involved in leukocyte adhesion. The current study aimed to investigate whether leukocyte-expressed TM promotes cell adhesion by interacting with Ley. Using human monocytic THP-1 cells as an in vitro cell model, we showed that TM increases THP-1 cell adhesion to inflamed endothelium as well as to Ley-immobilized surface. When THP-1 adhered to activated endothelium and Ley-immobilized surface, the TM distribution became polarized. Addition of soluble Ley to a suspension of THP-1 cells with TM expression triggered an increase in the level of phosphorylated p38 mitogen-activated protein kinase (MAPK), which enabled THP-1 to adhere firmly to intercellular adhesion molecule (ICAM)-1 by activating ß2 integrins. In vivo, macrophage infiltration and neointima formation following arterial ligation-induced vascular injury were higher in wild-type TM (TMflox/flox) than in myeloid-specific TM-deficient (LysMcre/TMflox/flox) mice. Taken together, these results suggest a novel function for TM as an adhesion molecule in monocytes, where it enhances cell adhesion by binding Ley, leading to ß2 integrin activation via p38 MAPK.

Acute Hepatotoxicity of Intravenous Amiodarone: Case Report and Review of the Literature.

Amiodarone is a class III antiarrhythmic drug widely used for the treatment of both supraventricular and ventricular arrhythmias in intensive care unit. Hepatotoxicity of amiodarone is usually mild and delayed onset. Acute hepatotoxicity is a rare side effect and usually correlated to intravenous form use. In this case, acute hepatocellular injury occurred within 24 hours after the administration of intravenous amiodarone. Liver enzyme significantly improved after holding intravenous amiodarone use. Because ventricular arrhythmia persisted and side effects occurred to alternative therapy, low dose of oral amiodarone was resumed and hepatotoxicity did not occur afterward. Acute hepatotoxicity of intravenous amiodarone is possibly related to polysorbate 80, the solubilizer of amiodarone infusion or higher dose. As a result, when intravenous amiodarone is prescribed, closely monitoring liver enzyme is highly suggested. If acute hepatitis takes place secondary to intravenous amiodarone, oral therapy should not be resumed afterward. If there is no alternative treatment, lower dose of oral amiodarone (≤200 mg/d) could be tried and should monitor liver function regularly.

The endothelin-integrin axis is involved in macrophage-induced breast cancer cell chemotactic interactions with endothelial cells.

Elevated macrophage infiltration in tumor tissues is associated with breast cancer metastasis. Cancer cell migration/invasion toward angiogenic microvasculature is a key step in metastatic spread. We therefore studied how macrophages stimulated breast cancer cell interactions with endothelial cells. Macrophages produced cytokines, such as interleukin-8 and tumor necrosis factor-α, to stimulate endothelin (ET) and ET receptor (ETR) expression in breast cancer cells and human umbilical vascular endothelial cells (HUVECs). ET-1 was induced to a greater extent from HUVECs than from breast cancer cells, resulting in a density difference that facilitated cancer cell chemotaxis toward HUVECs. Macrophages also stimulated breast cancer cell adhesion to HUVECs and transendothelial migration, which were repressed by ET-1 antibody or ETR inhibitors. The ET axis induced integrins, such as αV and ß1, and their counterligands, such as intercellular adhesion molecule-2 and P-selectin, in breast cancer cells and HUVECs, and antibodies against these integrins efficiently suppressed macrophage-stimulated breast cancer cell interactions with HUVECs. ET-1 induced Ets-like kinase-1 (Elk-1), signal transducer and activator of transcription-3 (STAT-3), and nuclear factor-κB (NF-κB) phosphorylation in breast cancer cells. The use of inhibitors to prevent their phosphorylation or ectopic overexpression of dominant-negative IκBα perturbed ET-1-induced integrin αV and integrin ß1 expression. The physical associations of these three transcriptional factors with the gene promoters of the two integrins were furthermore evidenced by a chromatin immunoprecipitation assay. Finally, our mouse orthotopic tumor model revealed an ET axis-mediated lung metastasis of macrophage-stimulated breast cancer cells, suggesting that the ET axis was involved in macrophage-enhanced breast cancer cell endothelial interactions.

Secreted heat shock protein 90α (HSP90α) induces nuclear factor-κB-mediated TCF12 protein expression to down-regulate E-cadherin and to enhance colorectal cancer cell migration and invasion.

Secreted levels of HSP90α and overexpression of TCF12 have been associated with the enhancement of colorectal cancer (CRC) cell migration and invasion. In this study, we observed that CRC patients with tumor TCF12 overexpression exhibited both a higher rate of metastatic occurrence and a higher average serum HSP90α level compared with patients without TCF12 overexpression. Therefore, we studied the relationship between the actions of secreted HSP90α and TCF12. Like overexpressed TCF12, secreted HSP90α or recombinant HSP90α (rHSP90α) induced fibronectin expression and repressed E-cadherin, connexin-26, connexin-43, and gap junction levels in CRC cells. Consistently, rHSP90α stimulated invasive outgrowths of CRC cells from spherical structures during three-dimensional culture. rHSP90α also induced TCF12 expression in CRC cells. Its effects on CRC cell epithelial-mesenchymal transition, migration, and invasion were drastically prevented when TCF12 was knocked down. This suggests that TCF12 expression is required for secreted HSP90α to enhance CRC cell spreading. Through the cellular receptor CD91, rHSP90α facilitated the complex formation of CD91 with IκB kinases (IKKs) α and ß and increased the levels of phosphorylated (active) IKKα/ß and NF-κB. Use of an IKKα/ß inhibitor or ectopic overexpression of dominant-negative IκBα efficiently repressed rHSP90α-induced TCF12 expression. Moreover, κB motifs were recognized in the gene sequence of the TCF12 promoter, and a physical association between NF-κB and the TCF12 promoter was detected in rHSP90α-treated CRC cells. Together, these results suggest that the CD91/IKK/NF-κB signaling cascade is involved in secreted HSP90α-induced TCF12 expression, leading to E-cadherin down-regulation and enhanced CRC cell migration/invasion.

The Effects of Pharmacist-Led Medication Therapy Management on Medication Adherence and Use of Non-Steroidal Anti-Inflammatory Drug in Patients with Pre-End Stage Renal Disease.

Purpose: Patients with chronic kidney disease (CKD) are particularly vulnerable to the risks of polypharmacy, largely owing to various comorbid conditions. This vulnerability is further compounded by an escalated risk of renal function deterioration when exposed to nephrotoxic medications. As part of the national health insurance program in Taiwan, the pre-end-stage kidney disease patient care and education plan has included pharmaceutical care since October 2021. This study aims to explore the effect of pharmacist involvement in a multidisciplinary care team for patients with kidney disease in outpatient settings. Patients and Methods: This retrospective observational study was conducted at a single center. It analyzed data from May 2022 to May 2023, focusing on patients who received medication therapy management in the kidney disease pharmacist-managed clinic. The study assessed changes in patient medication adherence, non-steroidal anti-inflammatory drugs (NSAIDs) usage, CKD stage, and urine protein-to-creatinine ratio (UPCR) after pharmacist intervention. It also documented pharmacists' medication recommendations and the rate of acceptance by physicians. Results: A total of 202 patients who had at least two clinic visits were included in the study. After pharmacist intervention, the proportion of poor medication adherence reduced significantly from 67.8% to 43.1% (p<0.001). The proportion of NSAID users also decreased significantly from 19.8% to 8.4% (p=0.001). CKD stage showed a significant reduction (p=0.007), and the average UPCR improved from 2828.4 to 2111.0 mg/g (p<0.001). The pharmacists provided a total of 56 medication recommendations, with an acceptance rate of 86%. Conclusion: The involvement of pharmacists in the multidisciplinary care team can effectively provide medication-related recommendations, ensuring the effectiveness and safety of patients' medication use, and lead to better kidney function and lower proteinuria.

Time to positivity of Klebsiella pneumoniae in blood cultures as prognostic marker in patients with intra-abdominal infection: A retrospective study.

Klebsiella pneumoniae is a common causative pathogen of intra-abdominal infection with concomitant bacteraemia, leading to a significant mortality risk. The time to positivity (TTP) of blood culture is postulated to be a prognostic factor in bacteraemia caused by other species. Therefore, this study aimed to investigate the prognostic value of TTP in these patients. The single-centred, retrospective, observational cohort study was conducted between 1 July 2016 and 30 June 2021. All adult emergency department patients with diagnosis of intra-abdominal infection and underwent blood culture collection which yield K. pneumoniae during this period were enrolled. A total of 196 patients were included in the study. The overall 30-day mortality rate was 12.2% (24/196), and the median TTP of the studied cohort was 12.3 h (10.5-15.8 h). TTP revealed a moderate 30-day mortality discriminative ability (area under the curve 0.73, p < 0.001). Compared with the late TTP group (>12 h, N = 109), patients in the early TTP (≤12 h, N = 87) group had a significantly higher risk of 30-day morality (21.8% vs. 4.6%, p < 0.01) and other adverse outcomes. Furthermore, TTP (odds ratio [OR] = 0.79, p = 0.02), Pitt bacteraemia score (OR = 1.30, p = 0.03), and implementation of source control (OR = 0.06, p < 0.01) were identified as independent factors related to 30-day mortality risk in patients with intra-abdominal infection and K. pneumoniae bacteraemia. Therefore, physicians can use TTP for prognosis stratification in these patients.

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker.

BACKGROUND/AIM: Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. MATERIALS AND METHODS: Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. RESULTS: Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the E-cadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. CONCLUSION: Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.

Tetraphenylanthraquinone and Dihydroxybenzene-Tethered Conjugated Microporous Polymer for Enhanced CO2 Uptake and Supercapacitive Energy Storage.

Conjugated microporous polymers (CMPs) feature extended excellent porosity properties and fully conjugated electronic systems, making them highly effective for several uses, including photocatalysis, dye adsorption, CO2 capture, supercapacitors, and so on. These polymers are known for their high specific surface area and adjustable porosity. To synthesize DHTP-CMPs (specifically TPE-DHTP CMP and Anthra-DHTP CMP) with abundant nitrogen (N) and oxygen (O) adsorption sites and spherical structures, we employed a straightforward Schiff-base [4 + 2] condensation reaction. This involved using 2,5-dihydroxyterephthalaldehyde (DHTP-2CHO) as the primary building block and phenolic OH group source, along with two distinct structures: 4,4',4″,4"'-(ethene-1,1,2,2-tetrayl)tetraaniline (TPE-4NH2) and 4,4',4″,4"'-(anthracene-9,10-diylidenebis(methanediylylidene))tetraaniline (Anthra-4Ph-4NH2). The synthesized Anthra-DHTP CMP had a remarkable BET surface area (BETSA) of 431 m2 g-1. Additionally, it exhibited outstanding thermal stability, as shown by a T d10 of 505 °C. Furthermore, for practical implementation, the Anthra-DHTP CMP demonstrates a significant capacity for capturing CO2, measuring 1.85 mmol g-1 at a temperature of 273 K and 1 bar. In a three-electrode test, the Anthra-DHTP CMP has a remarkable specific capacitance of 121 F g-1 at 0.5 A g-1. Furthermore, even after undergoing 5000 cycles, it maintains a capacitance retention rate of 79%. Due to their outstanding pore characteristics, abundant N and O, and conjugation properties, this Anthtra-DHTP CMP holds significant potential for CO2 capture and supercapacitor applications. This work will pave the way for the development of materials based on DHTP-CMPs and their postmodification with additional groups, facilitating their use in photocatalysis, photodegradation, lithium battery applications, and so on.

Tissue Expression of Growth Differentiation Factor 11 in Patients with Breast Cancer.

Protein growth differentiation factor 11 (GDF11) plays crucial roles in cellular processes, including differentiation and development; however, its clinical relevance in breast cancer patients is poorly understood. We enrolled 68 breast cancer patients who underwent surgery at our hospital and assessed the expression of GDF11 in tumorous, ductal carcinoma in situ (DCIS), and non-tumorous tissues using immunohistochemical staining, with interpretation based on histochemical scoring (H-score). Our results indicated higher GDF11 expressions in DCIS and normal tissues compared to tumorous tissues. In addition, the GDF11 H-score was lower in the patients with a tumor size ≥ 2 cm, pathologic T3 + T4 stages, AJCC III-IV stages, Ki67 ≥ 14% status, HER2-negative, and specific molecular tumor subtypes. Notably, the patients with triple-negative breast cancer exhibited a loss of GDF11 expression. Spearman correlation analysis revealed associations between GDF11 expression and various clinicopathological characteristics, including tumor size, stage, Ki67, and molecular subtypes. Furthermore, GDF11 expression was positively correlated with mean corpuscular hemoglobin concentration and negatively correlated with neutrophil count, as well as standard deviation and coefficient of variation of red cell distribution width. These findings suggest that a decreased GDF11 expression may play a role in breast cancer pathogenesis.

Pretreatment Circulating Albumin, Platelet, and RDW-SD Associated with Worse Disease-Free Survival in Patients with Breast Cancer.

Objective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.

Development of a Humanized Antibody Targeting Extracellular HSP90α to Suppress Endothelial-Mesenchymal Transition-Enhanced Tumor Growth of Pancreatic Adenocarcinoma Cells.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α's ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.

TCF12 protein functions as transcriptional repressor of E-cadherin, and its overexpression is correlated with metastasis of colorectal cancer.

A correlation of TCF12 mRNA overexpression with colorectal cancer (CRC) metastasis was suggested by microarray data and validated by the survey of 120 patients. Thirty-three (27.5%) of the 120 patients showed tumor TCF12 mRNA overexpression and had a higher rate of metastatic occurrence (p = 0.020) and a poorer survival outcome (p = 0.014). Abundant TCF12 levels were also observed in human CRC cell lines such as SW620 and LoVo, but a relatively low level was detected in SW480 cells. Knockdown of TCF12 expression in SW620 and LoVo cells drastically reduced their activities of migration, invasion, and metastasis. Tight cell-cell contact and an increase in E-cadherin but a concomitant decrease in fibronectin were observed in TCF12-knockdown cells. Connexin 26, connexin 43, and gap-junction activity were also increased upon TCF12-knockdown. In contrast, ectopic TCF12 overexpression in SW480 cells facilitated fibronectin expression and cell migration and invasion activities but diminished cellular levels of E-cadherin, connexin 26, connexin 43, and gap junction. A physical association of TCF12 with the E-cadherin promoter was evidenced by chromatin immunoprecipitation assay. TCF12 was tightly correlated with cellular expression of Bmi1 and EZH2 and was co-immunoprecipitable with Bmi1 and EZH2, suggesting that TCF12 transcriptionally suppressed E-cadherin expression via polycomb group-repressive complexes. Clinically, TCF12 mRNA overexpression was also correlated with E-cadherin mRNA down-regulation in the tumor tissues of our 120 patients (p = 0.013). These studies suggested that TCF12 functioned as a transcriptional repressor of E-cadherin and its overexpression was significantly correlated with the occurrence of CRC metastasis.

The Competition of Yin and Yang: Exploring the Role of Wild-Type and Mutant p53 in Tumor Progression.

The protein p53 is a well-known tumor suppressor that plays a crucial role in preventing cancer development [...].

Prediction of 30-Day Mortality Using the Quick Pitt Bacteremia Score in Hospitalized Patients with Klebsiella pneumoniae Infection.

Purpose: Klebsiella pneumoniae is an important causative pathogen of nosocomial infections, resulting in poor prognosis owing to its hypervirulence and antibiotic resistance. A simplified quicker version of the Pitt bacteremia score (PBS) (qPitt) for acute illness severity measurement was developed recently. The goal of this study was to explore the prognostic value of qPitt in patients with K. pneumoniae infection. Patients and Methods: Demographic information and management strategies were retrospectively collected from the records of all adult patients who visited the emergency department between January 1, 2021, and December 31, 2021, with culture-positive K. pneumoniae. The qPitt score was calculated based on: temperature <36°C, systolic blood pressure ≤90 mmHg or vasopressor administration, respiratory rate ≥25 times/min or need of mechanical ventilation, altered mental status, and cardiac arrest event. The 30-day mortality prediction abilities of the qPitt were compared with the PBS, the sequential organ failure assessment (SOFA), and the quick sequential organ failure assessment (qSOFA) using receiver operating characteristic curves. Results: Data from 867 patients (57.8% men) with a mean age of 66.9 were compiled. The 30-day mortality rate of the enrolled patients was 13.4%, and the area under the curve (AUC) of the scoring systems were as follows: SOFA, 0.91 (95% confidence interval [CI]=0.89-0.93), qPitt, 0.87 (95% CI=0.84-0.89), PBS, 0.87 (95% CI=0.85-0.89), and qSOFA, 0.73 (95% CI=0.70-0.76). The AUC of qPitt was significantly higher than that of qSOFA (p<0.01) and similar to that of PBS (p=0.65).The qPitt also demonstrated excellent mortality discrimination ability in non-bacteremic patients, AUC= 0.85 (95% CI=0.82-0.88). Conclusion: The qPitt revealed excellent 30-day mortality prediction ability and also predicted mortality in non-bacteremic patients with K. pneumoniae infection. Clinicians can use this simplified scoring system to stratify patients earlier and initiate prompt treatment in high-risk patients.