Pregnancy outcomes of patients with positive anticentromere antibodies receiving in vitro fertilization-embryo transfer. / æŠ—ç€ä¸ç‚¹æŠ—ä½“é˜³æ€§æ‚£è€ ä½“å¤–å—ç²¾ç»“å±€åˆ†æž.

OBJECTIVES: To analyze the pregnancy outcomes in patients with positive anti-centromere antibodies (ACA) receiving in vitro fertilization (IVF)-embryo transfer (ET) and natural conception. METHODS: A case-control study was used to retrospectively analyze the clinical data of 3955 patients who received IVF-ET therapy and had the results of antinuclear antibody (ANA) spectrum at Zhejiang Provincial People's Hospital from June 2016 to June 2023. Patients with positive ACA and negative ACA were matched at a ratio of 1∶3 using propensity score matching. Embryo outcomes of IVF were compared between the two groups, and the impact of different fertilization methods and the use of immunosuppressants on pregnancy outcomes were analyzed using self-matching. The natural conception and disease progress were followed up for ACA-positive patients after IVF failure. RESULTS: The ACA-positive patients accounted for 0.86% of all IVF patients (34/3955) and 2.51% of total ANA-positive IVF patients. Regardless of whether patients received conventional IVF (c-IVF) or intracytoplasmic sperm injection (ICSI), the ACA-positive group exhibited significant differences in oocyte maturity and fertilization compared to the ACA-negative group (both P<0.01). Moreover, the ACA-positive group had a decreased number of D3 suboptimal embryos and D3 optimal embryos (both P<0.05). In 5 cases of ACA-positive patients who underwent ICSI cycles, the two pronucleus (2PN) rate did not increase compared to c-IVF cycles (P>0.05), and there was a decrease in the number of D3 high-quality embryos and D3 suboptimal embryos (both P<0.05). After 1-2 months of immuno-suppressant treatment, 12 ACA-positive patients underwent c-IVF/ICSI again, and there were no changes in egg retrieval and fertilization before and after medication (both P>0.05), but there was an improvement in the 2PN embryo cleavage rate (P<0.05). The number of embryos transferred was similar between the ACA-positive and negative groups, but the ACA-positive group had significantly lower embryo implantation rate and clinical pregnancy rate compared to the ACA-negative group (both P<0.05), with no significant differences in the miscarriage rate between the two groups (P>0.05). Twenty-seven ACA-positive patients attempted natural conception or artificial insemination after IVF failure, resulting in a total of 7 cases of clinical pregnancy. CONCLUSIONS: Serum ACA positivity may disrupt oocyte maturation and normal fertilization processes, with no improvement observed with ICSI and immunosuppressant use. However, ACA-positive patients may still achieve natural pregnancy.

[Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review].

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Characterization of pyruvate metabolism and citric acid cycle patterns predicts response to immunotherapeutic and ferroptosis in gastric cancer.

BACKGROUND: Gastric cancer is one of the most common malignancies of the digestive system with a high lethal rate. Studies have shown that inherited and acquired mutations in pyruvate metabolism and citric acid cycle (P-CA) enzymes are involved in tumorigenesis and tumor development. However, it is unclear how different P-CA patterns affect the tumor microenvironment (TME), which is critical for cancer progression. METHODS: This study mainly concentrated on investigating the role of the P-CA patterns in multicellular immune cell infiltration of GC TME. First, the expression levels of P-CA regulators were profiled in GC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts to construct a consensus clustering analysis and identify three distinct P-CA clusters. GSVA was conducted to reveal the different biological processes in three P-CA clusters. Subsequently, 1127 cluster-related differentially expressed genes were identified, and prognostic-related genes were screened using univariate Cox regression analysis. A scoring system was then set up to quantify the P-CA gene signature and further evaluate the response of the patients to the immunotherapy. RESULTS: We found that GC patients in the high P-CA score group had a higher tumor mutational burden, higher microsatellite instability, and better prognosis. The opposite was observed in the low P-CA score group. Interestingly, we demonstrated P-CA gene cluster could predict the sensitivity to immunotherapy and ferroptosis-induced therapy. CONCLUSION: Collectively, the P-CA gene signature in this study exhibits potential roles in the tumor microenvironment and predicts the response to immunotherapeutic. The identification of these P-CA patterns may significantly accelerate the strategic development of immunotherapy for GC.

Impact of Patient Education via WeChat on Bowel Preparation for Colonoscopy: A Meta-analysis of Randomized Controlled Trials.

The aim of this study was to evaluate the impact of education via WeChat on the quality of bowel preparation in patients undergoing colonoscopy through a meta-analysis of randomized controlled trials. Randomized controlled trials of bowel preparation education provided via WeChat for patients undergoing colonoscopy were screened from databases such as PubMed, Web of Science, Cochrane Library, and Embase. Papers published from the date of database construction to May 1, 2021, were extracted, and a meta-analysis was performed using Review Manager software. A total of four randomized controlled trials were included in the meta-analysis. The results showed that for patients undergoing colonoscopy, education via WeChat significantly improves the quality of bowel preparation for colonoscopy, reduces the insertion time, and increases the adenoma detection rate and the patient's compliance and willingness to repeat bowel preparation. In conclusion, education via WeChat before colonoscopy can significantly improve the quality of bowel preparation.

Responses of CD27+ CD38+ plasmablasts, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells during primary dengue virus 2 infection.

BACKGROUND: Humoral immunity is thought to play a central role in mediating the immunopathogenesis of dengue virus (DENV) infection; however, the B-cell responses elicited by primary DENV2 infection are incompletely understood. Follicular helper T cells (Tfh) are important to promote B-cell activation and differentiation. METHODS: The present study analyzed the detailed dynamic changes of circulating B-cell subsets and Tfh (cTfh) using flow cytometry to explore their responses to DENV2 infection. RESULTS: Thirty-six patients with DENV2 and 21 healthy individuals were included. The results showed that CD27+ CD38+ plasmablasts emerged after DENV2 infection, and correlated with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh, which increased after DENV2 infection, and correlated with DENV2 RNA viral loads. Significantly low levels of CD27- naïve B cells, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells (Breg) were observed after DENV2 infection, which correlated negatively with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh cells. CONCLUSION: Overall, these results provide insights into the DENV2-elicited B-cell response and revealed previously unidentified CD24hi CD27hi and CD24hi CD38hi Breg responses to DENV2 infection.

Association of the Triglyceride to High-Density Lipoprotein Ratio and the Visceral Adiposity Index with Metabolic Syndrome in Diabetic Susceptible Population.

The aim of this study was to explore the association of the triglyceride to high-density lipoprotein ratio (TG/HDL) and the visceral adiposity index (VAI) with metabolic syndrome (Mets) in high-risk populations of diabetic patients. Patients were recruited from the Endocrinology Clinic of Hebei General Hospital from April 2018 to April 2019,according to the "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 Edition)". A total of 824 patients participated in the study. The association between TG/HDL or VAI and Mets in these patients was assessed using a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of TG/HDL and VAI to predict Mets in the diabetic susceptible population. The prevalence of Mets gradually increased in males and females with advancing tertiles of TG/HDL or VAI. After adjusting for the relevant risk factors, TG/HDL and VAI were positively correlated with Mets in men and women. Both of them showed a better the area under the ROC curve (AUC) for Mets in females than body mass index, waist circumference, TG and homeostatic model assessment of insulin resistance. In females, the cut-off point of 1.67 for VAI showed a higher accuracy for Mets (sensitivity 0.756, specificity 0.705, Youden index 0.461), the same relationship not significant in men. TG/HDL and VAI provide a high predictive value for Mets in a diabetic susceptible population, especially in females.

Does delayed esophagectomy after endoscopic resection affect outcomes in patients with stage T1 esophageal cancer? A propensity score-based analysis.

BACKGROUND: Although endoscopic resection (ER) may be sufficient treatment for early-stage esophageal cancer, additional treatment is recommended when there is a high risk of cancer recurrence. It is unclear whether delaying esophagectomy by performing and assessing the success of ER affects outcomes as compared with immediate esophagectomy without ER. Additionally, long-term survival after sequential ER and esophagectomy required further investigation. METHODS: Between 2011 and 2015, 48 patients with stage T1 esophageal cancer underwent esophagectomy after ER with curative intent at our institution. Two-to-one propensity score methods were used to identify 96 matched-control patients who were treated with esophagectomy only using baseline patient, tumor characteristics and surgical approach. Time from initial evaluation to esophagectomy, relapse-free survival, overall survival, and postoperative complications were compared between the propensity-matched groups. RESULTS: In the ER + esophagectomy group, the time from initial evaluation to esophagectomy was significantly longer than in the esophagectomy only group (114 vs. 8 days, p < 0.001). The incidence of dense adhesion (p = 0.347), operative time (p = 0.867), postoperative surgical complications (p = 0.966), and postoperative length of hospital stay (p = 0.125) were not significantly different between the groups. Moreover, recurrence-free survival and overall survival were also similar between the two groups (p = 0.411 and p = 0.817, respectively). CONCLUSIONS: Treatment of stage T1 esophageal cancer with ER prior to esophagectomy did not increase the difficulty of performing esophagectomy or the incidence of postoperative complications and did not affect survival after esophagectomy. These results suggest that ER can be recommended for patients with stage T1 cancer even if esophagectomy is warranted eventually.

Quality specifications of routine clinical chemistry methods based on sigma metrics in performance evaluation.

INTRODUCTION: Sigma metrics were applied to evaluate the performance of 20 routine chemistry assays, and individual quality control criteria were established based on the sigma values of different assays. METHODS: Precisions were expressed as the average coefficient variations (CVs) of long-term two-level chemistry controls. The biases of the 20 assays were obtained from the results of trueness programs organized by National Center for Clinical Laboratories (NCCL, China) in 2016. Four different allowable total error (TEa) targets were chosen from biological variation (minimum, desirable, optimal), Clinical Laboratory Improvements Amendments (CLIA, US), Analytical Quality Specification for Routine Analytes in Clinical Chemistry (WS/T 403-2012, China) and the National Cholesterol Education Program (NECP). RESULTS: The sigma values from different TEa targets varied. The TEa targets for ALT, AMY, Ca, CHOL, CK, Crea, GGT, K, LDH, Mg, Na, TG, TP, UA and Urea were chosen from WS/T 403-2012; the targets for ALP, AST and GLU were chosen from CLIA; the target for K was chosen from desirable biological variation; and the targets for HDL and LDL were chosen from the NECP. Individual quality criteria were established based on different sigma values. CONCLUSIONS: Sigma metrics are an optimal tool to evaluate the performance of different assays. An assay with a high value could use a simple internal quality control rule, while an assay with a low value should be monitored strictly.

Reciprocal relationship of Tn/NF-κB and sTn as an indicator of the prognosis of oral squamous cell carcinoma.

AIMS: In order to determine whether the expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-κB (NF-κB), is associated with the invasiveness of oral squamous cell carcinoma (OSCC), this study has attempted to investigate the correlation of the aforementioned markers with the well-established invasive pattern grading score (IPGS) and clinicopathological parameters. METHODS AND RESULTS: Specimens from 143 OSCC patients with classified clinicopathological parameters and IPGS were stained immunohistochemically using anti-Tn, sTn and NF-κB antibodies. Our results showed that the expression of both Tn and NF-κB was correlated positively with staging (P = 0.036; P = 0.015), recurrence (P < 0.001; P < 0.001) and distant metastasis (P = 0.005; P = 0.009), as well as with IPGS, while the expression of sTn was correlated inversely. In addition, poor survival was associated with overexpression of Tn and NF-κB but not with expression of sTn. CONCLUSIONS: Our results indicate that a reciprocal relationship between Tn and sTn expression may serve as a reliable indicator for OSCC prognostic evaluation. In addition, expression of Tn rather than sTn may play an important role in deeply invasive OSCC via regulation of NF-κB signalling.

The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the leading causes of cancer-related death worldwide. The prognosis of HNSCC is usually poor because of its propensity for extensive invasion, local recurrence and frequent regional lymph node metastasis, even at initial diagnosis. Carcinoma-associated fibroblasts (CAFs), a major type of tumour-surrounding stromal cell, generate mediators through which they interact with tumours and contribute to cancer progression. The orchestration between CAFs and cancer cells is complex. Despite recent studies demonstrating the paracrine effect of stromal cells in the tumour microenvironment on initiation and progression of cancer cells, the major mediator related to CAFs and its underlying mechanism remain unknown. In the present study, we used organotypic culture to investigate CAFs that promote aggressive behaviour of HNSCC cells. Using microarray analysis, we detected abundant expression of interleukin-33 (IL-33) in CAFs and identified IL-33 as a critical mediator in CAF-induced invasiveness. Counteracting IL-33 activity diminished the aggressive phenotype of cancer cells induced by CAFs. Administration of IL-33 promoted cancer cell migration and invasion through induction of epithelial-to-mesenchymal transdifferentiation and increased IL-33 gene expression in cancer cells. In 40 patients with HNSCC, IL-33 expression in CAFs correlated with IL-33 expression in cancer cells. Most cases with a low invasion pattern grading score (IPGS) showed low or no expression of IL-33, whereas most HNSCC cases with high IPGS displayed over-expression of IL-33 in CAFs and cancer cells. High IL-33 expression associated with poor prognosis in terms of nodal metastasis-free survival. These results indicate that CAFs promote cancer invasiveness via paracrine and autocrine effects on microenvironmental IL-33 signalling, and suggest that IL-33 is a potential prognostic biomarker that could be considered in therapeutic strategies for the treatment of patients with HNSCC.

Interleukin-8/CXCR1 Signaling Contributes to the Progression of Pulmonary Adenocarcinoma Resulting in Malignant Pleural Effusion.

Pulmonary adenocarcinoma (PADC) treatment limited efficacy in preventing tumor progression, often resulting in malignant pleural effusion (MPE). MPE is filled with various mediators, especially interleukin-8 (IL-8). However, the role of IL-8 and its signaling mechanism within the fluid microenvironment (FME) implicated in tumor progression warrants further investigation. Primary cultured cells from samples of patients with MPE from PADC, along with a commonly utilized lung cancer cell line, were employed to examine the role of IL-8 and its receptor, CXCR1, through comparative analysis. Our study primarily assessed migration and invasion capabilities, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties. Additionally, IL-8 levels in MPE fluid versus serum, along with immunohistochemical expression of IL-8/CXCR1 signaling in tumor tissue and cell blocks were analyzed. IL-8/CXCR1 overexpression enhanced EMT and CSC properties. Furthermore, the immunocytochemical examination of 17 cell blocks from patients with PADC and MPE corroborated the significant correlation between upregulated IL-8 and CXCR1 expression and the co-expression of IL-8 and CXCR1 in MPE with distant metastasis. In summary, the IL-8/ CXCR1 axis in FME is pivotal to tumor promotion via paracrine and autocrine signaling. Our study provides a therapeutic avenue for improving the prognosis of PADC patients with MPE.

Cancer-Associated-Fibroblast-Mediated Paracrine and Autocrine SDF-1/CXCR4 Signaling Promotes Stemness and Aggressiveness of Colorectal Cancers.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas. / èƒ°è ºç™Œç»†èƒžå’Œè¡€æ¸ å®Œæ•´è›‹ç™½è´¨N-糖基化特征的质谱分析.

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

OBJECTIVE: To evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma. METHODS: Patients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed. Cox regression model was used to elucidate risk factors for recurrence. RESULTS: Two hundred fifty-eight patients receiving WR and 1245 patients receiving segmentectomy were included. The mean follow-up time was 36.87 ± 16.21 months. Five-year recurrence-free survival following WR was 96.89% for patients with ground-glass nodule (GGN) ≤2 cm and 0.25< consolidation-to-tumor ratio (CTR) ≤0.5, not statistically different from 100% for those with GGN≤2 cm and CTR ≤0.25 (P = .231). The 5-year recurrence-free survival was 90.12% for patients with GGN between 2 and 3 cm and CTR ≤0.5, significantly lower than that of patients with GGN ≤2 cm and CTR ≤0.25 (P = .046). For patients with GGN≤2 cm and 0.25

Pulmonary benign metastasizing leiomyoma from uterine leiomyoma.

BACKGROUND: Benign metastasizing leiomyoma (BML) occurs in a low proportion of uterine leiomyomas and treatment methods for BML are diverse and controversial. The study introduces preliminary experiences in the diagnosis and treatment of BML with the purpose of finding a suitable management strategy for these patients. METHODS: Three patients with BML were treated in our department from April 2008 to July 2012. Each of these patients presented with multiple nodules in both lungs, where we performed video-assisted thoracoscopic wedge resection to harvest enough tissue for histopathologic and immunohistochemical examination. The patients were treated with medical castration or surgical castration after the diagnosis of BML. RESULTS: The ultimate pathologic results ruled out the possibility of leiomyosarcoma and other metastatic diseases, and confirmed that the pulmonary lesions were BML. The lung lesions remained stable in two patients who were treated by surgical castration, and the lung nodules regressed in one patient treated with gonadotropin-releasing hormone analogues. CONCLUSIONS: The diagnosis of BML is based on the medical history of uterine myomas and histopathologic and immunohistochemical examination of lung nodules. Video-assisted thoracoscopic wedge resection is the best way to harvest tissue for diagnosis. The better outcomes in BML seem to call for medical intervention, either chemical or surgical, after diagnosis is made.

Effect of Various Airborne Particle Abrasion Conditions on Bonding between Polyether-Ether-Ketone (PEEK) and Dental Resin Cement.

The effects of alumina particle size and jet pressure on the bond strength of polyetheretherketone (PEEK) were examined to determine the airborne particle abrasion parameters with minimal effects on PEEK and to achieve optimal bond strength, as a reference for future clinical use. An alumina particle with four particle sizes and three jet pressures was used to air-abrade PEEK. Surface roughness (Ra), morphology, chemical structure, and wettability were analyzed using a stylus profilometer, scanning electron microscope, X-ray diffractometer, and contact angle analyzer, respectively. The shear bond strength (SBS) of PEEK and dental resin cement was analyzed using a universal testing machine (n = 10). The failure modes and debonded fracture surfaces were observed using optical microscopy. Airborne particle abrasion increased the Ra and hydrophobicity of PEEK and deposited alumina residues. The SBS generally decreased after thermal cycling. A large particle size damaged the PEEK surface. The effects of different particle sizes and jet pressures on the SBS were only significant in certain groups. Adhesive failure was the main mode for all groups. Within the limitations of this study, 110 µm grain-sized alumina particles combined with a jet pressure of 2 bar prevented damage to PEEK, providing sufficient SBS and bonding durability between PEEK and dental resin cement.

Quantitative analysis of fucosylated glycoproteins by immobilized lectin-affinity fluorescent labeling.

Human biofluids are often used to discover disease-specific glycosylation, since abnormal changes in protein glycosylation can discern physiopathological states. Highly glycosylated proteins in biofluids make it possible to identify disease signatures. Glycoproteomic studies on saliva glycoproteins showed that fucosylation was significantly increased during tumorigenesis and that glycoproteins became hyperfucosylated in lung metastases, and tumor stage is associated with fucosylation. Quantification of salivary fucosylation can be achieved by mass spectrometric analysis of fucosylated glycoproteins or fucosylated glycans; however, the use of mass spectrometry is non-trivial for clinical practice. Here, we developed a high-throughput quantitative method, lectin-affinity fluorescent labeling quantification (LAFLQ), to quantify fucosylated glycoproteins without relying on mass spectrometry. Lectins with a specific affinity for fucoses are immobilized on the resin and effectively capture fluorescently labeled fucosylated glycoproteins, which are further quantitatively characterized by fluorescence detection in a 96-well plate. Our results demonstrated that serum IgG can be accurately quantified by lectin and fluorescence detection. Quantification in saliva showed significantly higher fucosylation in lung cancer patients compared to healthy controls or other non-cancer diseases, suggesting that this method has the potential to quantify stage-related fucosylation in lung cancer saliva.

Cytoplasmic CD133 expression is a reliable prognostic indicator of tumor regression after neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer.

BACKGROUND: Despite development in therapeutic strategies, such as neoadjuvant concurrent chemoradiotherapy (CCRT), the prognosis of colorectal cancer remains relatively poor. Cancer stem cells (CSC) with several characteristics can lead to therapeutic resistance. CD133 has been identified as a putative CSC marker in colorectal cancer; however, its functional role still needs elucidation. We verified the role of CD133 with emphasis on expression location and correlated the results of CD133 with clinical outcome in colorectal cancer. METHODS: We used immunohistochemistry to investigate the expression of CD133 in samples from 157 patients with colonic adenocarcinoma and from 76 patients with rectal adenocarcinoma who received neoadjuvant CCRT. We also correlated the expression location of CD133 with the clinicopathological parameters and prognosis. RESULTS: CD133 protein was variably overexpressed in colorectal cancer tissues and was present in three locations: apical and/or endoluminal surfaces, cytoplasm, and lumen. Cytoplasmic CD133 expression level correlated significantly with tumor local recurrence (P = 0.025) and survival of patients with colorectal cancer (P = 0.002), and correlated inversely with tumor regression grading (P = 0.021) after CCRT in patients with rectal cancer. CONCLUSIONS: The expression of CD133 in the cytoplasm is closely associated with local recurrence and patient survival, and may provide a reliable prognostic indicator of tumor regression grading in patients with rectal cancer after CCRT. Cytoplasmic CD133 expression may also help identify the surviving cancer cells in areas with nearly total regression after CCRT.

The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells.

BACKGROUND: To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential. METHODS: We used GSP to investigate SCC-25 cells with wild-type p53 gene and OEC-M1 cells with mutant p53 gene for the assessment of antiproliferative effects including cell viability, cell cycle, apoptosis, migration and invasion potential, and alterations of associated oncoproteins involved in cellular and molecular events. RESULTS: The findings suggest that GSP on OEC-M1 cells leads to cell cycle arrest by increasing the expression of p21(Cip1) /p27(Kip1) protein without functioning mitochondria-mediated apoptosis, whereas GSP on SCC-25 cells inhibits cell proliferation via both G1-phase arrest and mitochondria-mediated apoptosis in a dose-dependent manner as a result of alterations of Bcl-2. GSP also inhibits the migration and invasion of both cells, which are associated with the suppression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9. CONCLUSION: Antiproliferative effectiveness of GSP is closely associated with the p53 status of OSCC cells. GSP displays chemoadjuvant potential via cell cycle blockage and apoptotic induction. Our findings clearly suggest that GSP may play a role as a novel chemopreventive or therapeutic agent for OSCC.

Role of human papillomavirus infection in carcinogenesis of oral squamous cell carcinoma with evidences of prognostic association.

BACKGROUND: Betel nut chewing, cigarette smoking and alcohol drinking are thought to be major environmental risk factors responsible for the development of oral squamous cell carcinomas. Oncogenic human papillomavirus infections have a well-established association with uterine cervical carcinoma. However, little is known about the exact role of human papillomavirus infections in oral squamous cell carcinomas. This study is designed to elucidate the role of human papillomavirus infections in cancer development and prognosis of oral squamous cell carcinomas. METHODS: Molecular techniques including in situ hybridization and immunohistochemistry of p16(INK4A) and p53 for evidences of human papillomavirus in tissue micro-arrays were investigated. RESULTS: Twenty-four of 65 cases of oral squamous cell carcinomas were found positive for in situ hybridization and 14 were found positive for p16(INK4A). The majority of cases without the evidence of human papillomavirus were related to p53 over-expression. There were statistically significant correlations between the results of human papillomavirus test and size or extent of the tumor (P = 0.003) or the stage of oral squamous cell carcinomas (P = 0.015). Kaplan-Meier plot analysis demonstrated a tendency of longer survival in cases of oral squamous cell carcinomas with the evidence of human papillomavirus or positive p16 (INK4A). CONCLUSIONS: Human papillomavirus infections may play a unique role in oral carcinogenesis. Our data strongly suggest that human papillomavirus-positive oral squamous cell carcinomas comprise a distinct clinical and pathological disease entity that appears related to a better outcome with longer survival and bears a causally associated relationship different from other carcinogenic mechanisms.