Tumor clinicopathological characteristics and their prognostic value in mucinous colorectal carcinoma.

Aim: This study analyzed clinicopathological features of colorectal mucinous carcinoma and their prognostic values. Patients & method: This study enrolled 265 patients with mucinous colorectal cancer. Clinicopathological information and prognosis were reviewed retrospectively. Kaplan-Meier method, log- rank test and COX proportional hazard regression models were used. Results: In postoperative mucinous carcinoma patients (median age 56, 119 [44.9%] female), advanced tumor stage (odds ratio [OR]: 2.378; 95% CI: 1.512-3.741; p = 0.0002), poor differentiation (OR: 1.896; CI: 1.217-2.955; p = 0.0047) and right-sided tumors (OR: 2.421; CI: 1.145-5.102; p = 0.0206) were associated with shorter overall survival. Appendiceal/ileocecal cecal tumors were not different for prognosis. Conclusion: Mucinous colorectal carcinoma exhibits distinct tumor characteristics. Poor differentiation, advanced stage at presentation and the right side serve as negative prognostic factors.

Penalized variable selection in competing risks regression.

Penalized variable selection methods have been extensively studied for standard time-to-event data. Such methods cannot be directly applied when subjects are at risk of multiple mutually exclusive events, known as competing risks. The proportional subdistribution hazard (PSH) model proposed by Fine and Gray (J Am Stat Assoc 94:496-509, 1999) has become a popular semi-parametric model for time-to-event data with competing risks. It allows for direct assessment of covariate effects on the cumulative incidence function. In this paper, we propose a general penalized variable selection strategy that simultaneously handles variable selection and parameter estimation in the PSH model. We rigorously establish the asymptotic properties of the proposed penalized estimators and modify the coordinate descent algorithm for implementation. Simulation studies are conducted to demonstrate the good performance of the proposed method. Data from deceased donor kidney transplants from the United Network of Organ Sharing illustrate the utility of the proposed method.

MACC1 overexpression and survival in solid tumors: a meta-analysis.

Metastasis associated in colon cancer-1 (MACC1) is a newly identified oncogene, and increasing evidence has suggested that its overexpression is associated with the development and progression in many tumors. Here, we perform a meta-analysis to assess the relationship between MACC1 overexpression and survival in solid tumors. Eligible studies were searched in Embase, PubMed, and Web of Science databases up to May 2014. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the impact of MACC1 overexpression on survival using a random-effect model. A total of 20 eligible studies dealing with various tumors were included in the analysis: 17 were dealing with overall survival (OS), 7 were with relapse-free survival (RFS), and 3 were with disease-free survival (DFS). Combined results suggested a strong link between the high MACC1 expression and the poor overall survival (HR 2.11, 95% CI 1.59-2.80, P < 0.001). For relapse-free survival, overexpressed MACC1 was also a significant predictor, with a combined HR of 2.22 (95% CI 1.80-2.74, P < 0.001). Data from the three studies were combined to show that MACC1 overexpression had also an unfavorable impact on disease-free survival (HR 2.94, 95% CI 1.60-5.38, P < 0.001). Publication bias was not significant. The present meta-analysis showed that overexpression of MACC1 was significantly associated with poorer survival in solid tumors.

The crosstalk: Tumor-infiltrating lymphocytes rich in regulatory T cells suppressed cancer-associated fibroblasts.

BACKGROUND: The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. MATERIAL AND METHODS: The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. RESULTS: Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. CONCLUSION: CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner.

Strategies for dealing with missing data in clinical trials: from design to analysis.

Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.

[Clinical observation of lymphangiectasis in conjunctivochalasis cases].

OBJECTIVE: To investigate the relationship between the occurrence and development of conjunctivochalasis and bulbar conjunctival lymphangiectasia. METHODS: Case control study. One hundred cases with conjunctivochalasis treated from January to March 2012 were selected to study, and 100 cases with no conjunctivochalasis as the control group at the same time. To observe bulbar conjunctiva lymphatic duct dilatation using slit lamp microscope, analysis bulbar conjunctiva and fascia images by OCT scanning, and ablate lymphatic of conjunctival tissue for pathologic examine. RESULTS: Twenty-nine eyes of the bulbar conjunctiva lymphangiectasia associated with 100 cases (183 eyes) conjunctivochalasis patients, accounting for 15.84%; 8 eyes of the ball conjunctival lymphatic dilation in control group of 100 cases ( 200 eyes), accounting for 4.00%. The difference between the two groups was statistically significant (χ(2) = 15.36, P < 0.001). OCT scanning showed that lymphangiectasia of the conjunctiva is at the subcutaneous mainly, some in the conjunctival lamina propria. They are border-clear, full-filled fluid, single-lumen or multi lumens, not involving the fascia. The histopathological examination showed that the lamina propria of the bulbar conjunctiva mildly chronic inflammatory changes accompanied by a large number of lymphangiectasia. CONCLUSION: Bulbar conjunctival lymphangiectasia may be one of the reasons for the conjunctivochalasis.

Heregulin-ß1-induced GPR30 upregulation promotes the migration and invasion potential of SkBr3 breast cancer cells via ErbB2/ErbB3-MAPK/ERK pathway.

Estrogen receptor (ER)-negative breast cancer cells are probably more aggressive with larger metastatic potential than ER-positive cells. Loss of ER in recurrent breast cancer is associated with poor response to endocrine therapy. G protein-coupled receptor 30 (GPR30) is expressed in half of ER-negative breast cancers. Tumor cell-derived heregulin-ß1 (HRG-ß1) is also found mainly in ER-negative cancer. In SkBr3 breast cancer cells that lack ER but express GPR30, HRG-ß1 upregulates mRNA and protein levels of GPR30 by promoting ErbB2-ErbB3 heterodimerization and activating the downstream MAPK-ERK signaling pathway. Moreover, GPR30 boosts HRG-ß1-induced migration and invasion of SkBr3 cells after combinative treatment with E2, 4-hydroxy-tamoxifen or the specific GPR30 agonist G-1, which are blocked by the specific GPR30 antagonist G-15 or the transfection with the small interfering RNA for GPR30. The ErbB2 inhibitor AG825 and the MEK1/2 inhibitor U0126 also partly inhibit the enhanced migration and invasion. Therefore, HRG-ß1-induced migration and invasion partly depend on the upregulation of GPR30 expression through activation of the ErbB2-ERK pathway in SkBr3 cells. The results of this study indicate that the crosstalk between GPR30 and HRGs signaling is important for endocrine therapy resistance and may provide a new therapeutic way to treat breast cancer.

Plasma lipid-based machine learning models provides a potential diagnostic tool for colorectal cancer patients.

Colorectal cancer is the second leading cause of cancer-related death across the world. So far, screening method for colorectal cancer are limited to blood test, imaging test, and digital rectal examination, that are either invasive or ineffective. So, this study aims to explore novel, more convenient and effective diagnostic method for colorectal cancer. First, the experiment cohort was randomly split to train set and test set, and LC-MS-based plasma lipidomics was applied to identify lipid features in colorectal cancer. Second, univariate and multivariate analyses were performed to screen for significantly differentially expressed lipids. Third, single-lipid-based ROC analysis and multiple-lipid-based machine learning modeling were conducted to assess differential lipids' diagnostic performance. Lastly, survival analyses were used to evaluate lipids' prognostic values. In total, 41 differential lipids were screened out, 10 were upregulated and 31 were downregulated in CRC. Only CerP(d15:0_22:0 + O) showed fine predictive accuracy in single-lipid-based ROC analysis. Among the four machine learning models, SVM showed best predictive performance with accuracy (in predicting test set) of 1.0000 (95 %CI: 0.8806, 1.0000), that can be reached by modeling with only 14 lipids. Four lipids had significant prognostic values, that were TG(11:0_18:0_18:0) (HR: 0.34), TG(18:0_18:0_18:1) (HR: 0.34), PC(22:1_12:3) (HR: 2.22), LPC(17:0) (HR: 3.16). In conclusion, this study discovered novel lipid features that have potential diagnostic and prognostic values, and showed combination of plasma lipidomics and machine learning modeling could have outstanding diagnostic performance and may serve as a convenient and more accessible way to aid in clinical diagnosis of colorectal cancer.

CDH1 germline mutations in a Chinese cohort with hereditary diffuse gastric cancer.

PURPOSE: Germline mutations in CDH1 are associated with hereditary diffuse gastric cancer (HDGC) and have been identified in multiple ethnicities. However, CDH1 germline mutations have seldom been documented in Chinese patients with HDGC, and their frequency remains unclear. Here, we aimed to examine the frequency of CDH1 germline mutations in Chinese patients with HDGC. In total, 285 patients who met the International Gastric Cancer Linkage Consortium 2015 testing criteria of HDGC for CDH1 germline mutations were recruited. METHODS: All 16 CDH1 exons, including neighboring intronic sequences, were amplified using polymerase chain reaction and screened using Sanger sequencing. Variants were analyzed using Mutation Surveyor V4.0, SIFT, and PolyPhen-2 software. RESULTS: Three nonsense and nine missense CDH1 germline mutations were identified in 21 of 285 index cases (7.4%). Two CDH1 germline mutations, N405Y (Asn405Tyr) and W409X (Trp409Ter), were identified as new variants. In addition, up to 28.6% of CDH1 mutations in the 21 indicated patients were identified as c.1775G>C (E551Q). The frequency of CDH1 mutations was 6.5% (7/108) in HDGC and 7.9% (14/177) in early onset diffuse gastric cancer (EODGC). The mutation detection rates of CDH1 in males and females were 6.7% (4/60) and 8.5% (10/117) in EODGC and 4.6% (3/65) and 9.3% (4/43) in HDGC, respectively. CONCLUSION: These data reveal, for the first time, the type and frequency of CDH1 germline mutations in Chinese HDGC and demonstrate that germline CDH1 mutations are a noteworthy contributor to the high frequency of HDGC in Chinese.

[Removal Efficiency of Trichloroacetamide by UV/Sodium Sulfite].

Haloacetamides (HAcAms) are an emerging class of nitrogenous disinfection by-products (N-DBPs) with high cytotoxicity and genotoxicity, which are widely detected in drinking water. The toxicity of trichloroacetamide (TCAcAm) is significantly higher than traditional DBPs. In this study, ultraviolet (UV) treatment was combined with sodium sulphite (Na2SO3) to remove TCAcAm from water. The effects of different light intensities, different agent dosages (Na2SO3), and pH conditions on the removal of TCAcAm by UV/Na2SO3 advanced reduction process were investigated. The results showed that TCAcAm could be rapidly degraded by the UV/Na2SO3 system. The degradation effect was directly proportional to light intensity, dosage of Na2SO3, and pH. Moreover, the pH had a significant effect on the reaction rate and degradation rate. As the pH increased from 6 to 9, the degradation rate of TCAcAm increased from 12.8% to 99.6%, in 120 min. The removal rate of TCAcAm reached 99.4% when the UV light intensity, pH, Na2SO3 dosage, and reaction time were 450 µW·cm-2, 9, 1.00 mmol·L-1, and 30 min, respectively. The experimental results indicated that the UV/Na2SO3 system is an efficient advanced reduction process for the removal of TCAcAm, and it has the potential to reduce other halogenated DBPs. Therefore, it could be used for the degradation of halogenated DBPs in the treatment of drinking water.

Preparation, characterization, and in vivo study of rhein solid lipid nanoparticles for oral delivery.

In this study, rhein-SLNs were successfully produced by hot homogenization followed by ultrasonication. Precirol ATO5 in which rhein exhibited higher partition coefficient was selected for preparation of SLNs. In the dynamic light scattering, the rhein-SLNs showed a smaller size with a mean value of 120.8 ± 7.9 nm and with zeta potential of -16.9 ± 2.3 mV. SLNs exhibited a good stability during the period of 2 months. The SLNs indicated faster drug release with a burst release within 2 hr and followed by a sustained release with a biphasic drug-release pattern. Comparing with the same concentration (free drug), the cellular cytotoxicity of rhein-loaded SLNs increased significantly at the same incubation condition. In vivo, the AUC0-t of rhein in the form of SLNs was significantly increased and was 2.06-fold that of suspensions group. The results showed an increased oral absorption and improved the oral bioavailability of rhein by the formulation of SLNs.

Evaluation of Corneal Deformation Parameters Provided by the Corvis ST Tonometer After Trabeculectomy.

PURPOSE: The aims of this study were to evaluate how the corneal deformation parameters provided by the Corvis ST tonometer (CST) were influenced by pressure-lowering ocular surgery, and to determine the correlations of intraocular pressure (IOP) and axial length (AL) with CST corneal deformation parameters. METHODS: This prospective 1-month study enrolled 22 subjects (22 eyes) who underwent trabeculectomy combined with mitomycin C. The corneal deformation parameters were measured using the CST. IOP was measured before and after surgery by a Goldmann applanation tonometer and the CST. The central corneal thickness and AL were also recorded. The correlations of the corneal deformation parameters with central corneal thickness, AL, and IOP changes were determined by linear regression analysis. RESULTS: IOP decreased significantly after surgery. AL was significantly shorter at 1 week after surgery. There were significant changes in the CST parameters time 1, velocity 1, velocity 2, peak distance highest concavity, and deformation amplitude highest concavity at 1 week and 1 month after surgery and in time highest concavity at 1 week after surgery. The change in time 1 was significantly correlated with preoperative IOP and the IOP reductions, and was positively correlated with the decrease in AL at 1 week. The increase in velocity 1 was negatively correlated with preoperative IOP, and IOP reductions. The change in time highest concavity was negatively correlated with IOP before surgery and the decrease in IOP at 1 week. CONCLUSION: CST is a good choice for measuring IOP, especially when aiming for normalization of IOP after glaucoma surgery.

Smad3 mutant mice develop colon cancer with overexpression of COX-2.

Colon cancer is the second most common cause of cancer-associated mortality in human populations. The aim of the present study was to identify the role of cyclooxygenase-2 (COX-2) in Smad3 mutant mice, which are known to develop colon cancer. Homozygous Smad3 (-/-) mutant mice were generated from inbred and hybrid Smad3 mouse strains by intercrossing the appropriate heterozygotes. Immunohistochemistry with COX-2 antibody was performed throughout this experiment and the data was validated and cross-checked with reverse transcription-polymerase chain reaction (RT-PCR). Homozygous mutant Smad3 mice were generated and the overexpression pattern of COX-2 was identified by immunohistochemistry and validated with RT-PCR. The results of the present study demonstrated a link between the Smad3 mutant mice, colon cancer and COX-2. In addition, the overexpression pattern of COX-2 in Smad3 mutant mice that develop colon cancer was identified.

Factors Influencing Difficulty of Laparoscopic Abdominoperineal Resection for Ultra-Low Rectal Cancer.

PURPOSE: Our current study was conducted to identify patients' anatomic, pathologic, and clinical factors to predict difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. MATERIALS AND METHODS: Records of 117 consecutive patients with rectal cancer 2 to 5 cm from the anal verge were retrospectively reviewed. Using univariate and multivariate linear or logistic regression models, standardized operative time and blood loss, as well as postoperative morbidity were utilized as endpoints to screen patients' multiple variables to predict operative difficulty. RESULTS: Multivariate linear regression analysis showed body mass index (BMI) (estimate=0.07, P=0.0056), interspinous distance (estimate=-0.02, P=0.0011), tumor distance from anal verge (estimate=-0.17, P=0.0355), prior abdominal surgery (estimate=0.51, P=0.0180), preoperative chemoradiotherapy (estimate=0.67, P=0.0146), and concurrent diseases (hypertension and/or diabetes mellitus) (estimate=0.49, P=0.0122) are predictors for standardized operative time. Age (estimate=0.02, P=0.0208) and concurrent diseases (estimate=0.43, P=0.0476) were factors related to standardized blood loss. BMI (estimate=0.15, P=0.0472) was the only predictor for postoperative morbidity based on logistic regression analysis. CONCLUSIONS: Age, BMI, interspinous distance, tumor distance from anal verge, prior abdominal surgery, preoperative chemoradiotherapy, and concurrent diseases influence the difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. Standardized operative time allows researchers to amass samples by pooling data from all published studies, thus building reliable models to predict operative difficulty for clinical use.

Case report of a KIT-mutated melanoma patient with an excellent response to apatinib and temozolomide combination therapy.

Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2) and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ) is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation.

Comparison of perioperative outcomes between laparoscopic and open surgery for mid-low rectal cancer with total mesorectal excision following neoadjuvant chemoradiotherapy.

OBJECTIVE: The objective of our study was to determine the feasibility and safety of laparoscopic total mesorectal excision (TME) for mid-low rectal cancer following neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively reviewed the records of 172 patients with locally advanced rectal cancer who underwent laparoscopic (n = 75) or conventional open (n = 97) surgery with TME following nCRT from June 2009 to October 2015. Perioperative outcomes and related clinical variables were collected and statistically analyzed. RESULTS: Our results showed that patients who underwent laparoscopic surgery had significantly less blood loss and shorter time to pass first flatus and to start a liquid diet compared to those on open surgery. However, other perioperative outcomes, including operative times, postoperative morbidity rates, number of lymph nodes harvested, and sphincter preservation rates, were not significantly different between the two groups. After controlling for surgical approaches, we found that age, gender, tumor stages, and tumor distance to anal verge were significantly correlated with operative times in both groups. Likewise, age, body mass index, tumor T stages, and tumor distance to anal verge were predictors for postoperative morbidity in both groups. CONCLUSIONS: We concluded that laparoscopic TME following nCRT is feasible and safe for patients with mid-low rectal cancer. Furthermore, tumor distance to anal verge and age are two important determinants of both operative times and postoperative morbidity, regardless of surgical option.

Study of distinct serum proteomics for the biomarkers discovery in colorectal cancer.

To utilize surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to identify potential biomarkers for diagnosis, preoperative pathological classification, staging, and postoperative prognosis in patients with colorectal cancer (CRC), a total of 152 samples were analyzed in this study, including 53 untreated CRC, 12 colorectal adenoma, 15 healthy volunteers, 30 post-treatment CRC patients with stable disease, and 42 post-treatment CRC with progressive disease. The samples were all analyzed by SELDI-TOF-MS and CM10 ProteinChip technology. The proteomic profiles were validated using a bioinformatics tool based on support vector machine (SVM) and undecimated discrete wavelet transform (UDWT) methods. Seven protein peaks were selected as potential biomarkers for CRC, with a specificity of 85.19% and a sensitivity of 96.23%. Four protein peaks were selected as potential markers for colorectal mucinous adenocarcinoma and non-mucinous adenocarcinoma, with a specificity of 95.12% and sensitivity of 83.33%. In addition, SELDI-based serum profiling discriminated between patients with locally advanced (stage I-II) and regionally advanced (stage III) CRC, and between patients with locoregional (stage I-III) and systemic (stage IV) CRC, with high specificity and sensitivity. A protein peak at 5909 Da was identified as a potential marker for tumor progression and prognosis in CRC. In conclusion, we have demonstrated that ProteinChip technology with SELDI-TOF-MS could provide a novel, non-invasive tool for diagnosis, potential preoperative biomarkers for pathological classification, staging, and postoperative prognostic markers for patients with CRC.

Topo2A as a prognostic biomarker for patients with resectable esophageal squamous cell carcinomas.

Topoisomerase 2α (Topo2A) is a key enzyme in replication. It functions as a cell proliferation and cell cycle-specific marker and it is identified mainly in the interphase nuclei of proliferating cells. Many studies have shown that Topo2A protein expression is up-regulated in various cancers including esophageal cancer. However, to date, no studies have adequately addressed the prognostic value of Topo2A in patients with resectable esophageal squamous cell carcinoma (ESCC). Therefore, we conducted a large-scale retrospective study investigating the expression of Topo2A and the clinicopathological characteristics or prognosis of ESCC patients. Eight hundred and twenty-nine specimens of ESCC from patients who underwent complete esophageal cancer resection were evaluated using an immunohistochemical assay. Among them, 404 (48.7 %) cases with a score >2 were determined to be positive for Topo2A expression. Topo2A overexpression was significantly associated with poorer differentiation (P = 0.007) and perineural invasion (P = 0.046). The median progression-free survival (PFS) of 319 patients with Topo2A-positive expression and 336 patients with Topo2A-negative expression was 19.5 and 26.5 months, respectively (P = 0.000). The overall survival (OS) in patients with and without Topo2A expression was 34.0 and 44.5 months, respectively (P = 0.002). In the multivariate analysis, Topo2A overexpression was identified as an independent prognostic factor for PFS (P = 0.001) and OS (P = 0.009). We determined that Topo2A overexpression was not only associated with poorer differentiation and perineural invasion, but it could also act as an independent risk factor for ESCC.

Lower eyelid tension in young adults determined by a simple lid tensiometer.

PURPOSE: Eyelid tension seems to be related to corneal astigmatism and to affect the ocular surface. The aim of this study is to determine the lower eyelid tension in young adults with a simple lid tensiometer. METHODS: A commercially available precision digital pressure gauge that was connected to a pressure-guided tube full of water with a sensor at its end being placed between the lower eyelid and ocular surface was used as the lid tensiometer to measure the lower eyelid pressure at the central lid in 8 male and 12 female subjects aged between 20 and 39 years with normal healthy eyes. Measurements were respectively performed by 2 operators under the same conditions to test possible interoperator variation. RESULTS: The lower eyelid pressures of the 20 subjects measured by 2 operators at the central lid were 445.28 ± 121.17 and 458.65 ± 127.15 Pa, respectively. The test of interoperator variation demonstrated that there was good agreement between 2 operators (intraclass correlation coefficient = 0.965, F = 56.09, P < 0.001). CONCLUSIONS: Our simple lid tensiometer is a viable option for measuring eyelid pressure with good repeatability.

Cancer-associated fibroblasts from invasive breast cancer have an attenuated capacity to secrete collagens.

Normal fibroblasts produce extracellular matrix (ECM) components that form the structural framework of tissues. Cancer-associated fibroblasts (CAFs) with an activated phenotype mainly contribute to ECM deposition and construction of cancer masses. However, the stroma of breast cancer tissues has been shown to be more complicated, and the mechanisms through which CAFs influence ECM deposition remain elusive. In this study, we found that the activated fibroblast marker α-smooth muscle actin (α-SMA) was only present in the stroma of breast cancer tissue, and the CAFs isolated from invasive breast cancer sample remained to be activated and proliferative in passages. To further assess the difference between CAFs and normal breast fibroblasts (NFs), MALDI TOF/TOF­MS was used to analyze the secretory proteins of primary CAFs and NFs. In total, 2,903 and 3,023 proteins were identified. Mass spectrum quantitative assay and data analysis for extracellular proteins indicated that the CAFs produce less collagens and matrix-degrading enzymes compared with NFs. This finding was confirmed by western blot analysis. Furthermore, we discovered that reduced collagen deposition was present in the stroma of invasive breast cancer. These studies showed that although CAFs from invasive breast cancer possess an activated phenotype, they secreted less collagen and induced less ECM deposition in cancer stroma. In cancer tissue, the remodeling of stromal structure and tumor microenvironment might, therefore, be attributed to the biological changes in CAFs including their protein expression profile.