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This study aims to evaluate diagnostic accuracy of flow cytometry (FCM) in detecting malignant epithelial cells in serous effusions. Flow cytometric assessment of 96 serous fluids (86 ascitic, 10 pleural) was performed by using epithelial cell adhesion molecule (EpCAM) (in all 96 fluids) and MUC-1 (in a subgroup of 40 fluids) as epithelial markers and CD45 and CD14 as leucocyte markers. The percentage of EpCAM positivity and MUC-1 positivity was calculated in the CD14 and CD45 dual negative population by selective gating. The findings were then correlated with the defined gold standard criteria. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy for EpCAM was found to be 92.06%, 96.96%, 98.31%, 86.48%, and 93.75%, respectively, while that for MUC-1 was 79.16%, 93.75%, 95%, 71.4%, and 85%, respectively. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy for dual positivity for EpCAM and MUC-1 was found to be 83.3%, 100%, 100%, 80%, and 90% respectively. On combining FCM with cytomorphology the sensitivity, specificity, PPV, NPV, and diagnostic accuracy all increased greatly to 95.3%, 100%, 100%, 91.4%, and 96.8%, respectively. This study highlights the importance of multicolored flow cytometric analysis in detecting epithelial malignancies in effusions specially in cases belonging to the atypia of undetermined significance and suspicious for malignancy categories and in cases with strong clinical suspicion of malignancy with negative fluid cytology. We recommend the combined use of FCM and cytology for this specific subgroup of patients in routine clinical practice for fast and accurate reporting. • The study highlights the importance of multicolored flow cytometric analysis using EpCAM and MUC-1 in detecting epithelial malignancies in effusions specially for atypical and suspicious cases. • We recommend combined use of flow cytometry and cytology for this specific subgroup of patients in routine clinical practice for fast and accurate reporting. [ABSTRACT FROM AUTHOR]

Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo , and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC. [ABSTRACT FROM AUTHOR]

The Egyptian tortoise (Testudo kleinmanni) is remarkably adapted to its harsh desert environment, a characteristic that is crucial for its survival under extreme conditions. This study was aimed at providing a deeper understanding of the lingual salivary gland structures in the Egyptian tortoise and examining how these structures help the tortoise manage hydration and nutrition in arid conditions. Utilizing a combination of light microscopy and immunofluorescence, this research introduced pioneering methods involving seven different antibodies, marking a first in the study of reptilian salivary glands. Our investigations categorized the tortoise's salivary glands into papillary and non-papillary types. The papillary glands were further classified into superficial, deep, interpapillary, and intraepithelial salivary glands, while non-papillary glands included superficial and deep lingual types. Structurally, these glands are organized into lobules, delineated by interlobular septa, and are equipped with a duct system comprising interlobular, intercalated, and main excretory ducts with gland openings on the tongue's surface and the papillae surfaces. Notably, the superficial glands displayed both tubuloalveolar and acinar configurations, whereas the deep lingual glands were exclusively acinar. Immunofluorescence results indicated that α-smooth muscle actin (α-SMA) was prevalent in myoepithelial cells, myofibroblasts, and blood vessels, suggesting their integral role in glandular function and support. E-cadherin was predominantly found in epithelial cells, enhancing cell adhesion and integrity, which are critical for efficient saliva secretion. Importantly, Mucin 1 (MUC1) and Mucin 5B (MUC5B) staining revealed that most glands were mucous in nature, with MUC5B specifically marking mucin within secretory cells, confirming their primary function in mucous secretion. PDGFRα and CD34 highlighted the presence of telocytes and stromal cells within the glandular and interlobular septa, indicating a role in structural organization and possibly in regenerative processes. Cytokeratin 14 expression was noted in the basal cells of the glands, underscoring its role in upholding the structural foundation of the epithelial barrier. In conclusion, this detailed morphological and immunological characterization of the Egyptian tortoise's salivary glands provides new insights into their complex structure and essential functions. These findings not only enhance our understanding of reptilian physiology but also underline the critical nature of salivary glands in supporting life in arid environments. This study's innovative use of a broad range of immunofluorescence markers opens new avenues for further research into the adaptive mechanisms of reptiles. • Novel immunofluorescence study unveils salivary gland structure in Egyptian tortoise. • Immunofluorescence reveals α-SMA prevalence in myoepithelial cells, crucial for gland function. • E-cadherin ensures adhesion in epithelial cells; CK14 maintains integrity in basal cells. • MUC1 and MUC5B staining confirm mucous nature and primary function in secretion. • CD34 and PDGFRα highlight presence of telocytes and stromal cells in salivary gland. [ABSTRACT FROM AUTHOR]

Mechanisms contributing to the onset and progression of Barrett's (BE)-associated esophageal adenocarcinoma (EAC) remain elusive. Here, we interrogated the major signaling pathways deregulated early in the development of Barrett's neoplasia. Whole-transcriptome RNA sequencing analysis was performed in primary BE, EAC, normal esophageal squamous, and gastric biopsy tissues (n = 89). Select pathway components were confirmed by quantitative polymerase chain reaction in an independent cohort of premalignant and malignant biopsy tissues (n = 885). Functional impact of selected pathway was interrogated using transcriptomic, proteomic, and pharmacogenetic analyses in mammalian esophageal organotypic and patient-derived BE/EAC cell line models, in vitro and/or in vivo. The vast majority of primary BE/EAC tissues and cell line models showed hyperactivation of EphB2 signaling. Transcriptomic/proteomic analyses identified EphB2 as an endogenous binding partner of MYC binding protein 2, and an upstream regulator of c-MYC. Knockdown of EphB2 significantly impeded the viability/proliferation of EAC and BE cells in vitro/in vivo. Activation of EphB2 in normal esophageal squamous 3-dimensional organotypes disrupted epithelial maturation and promoted columnar differentiation programs, notably including MYC. EphB2 and MYC showed selective induction in esophageal submucosal glands with acinar ductal metaplasia, and in a porcine model of BE-like esophageal submucosal gland spheroids. Clinically approved inhibitors of MEK, a protein kinase that regulates MYC, effectively suppressed EAC tumor growth in vivo. The EphB2 signaling is frequently hyperactivated across the BE-EAC continuum. EphB2 is an upstream regulator of MYC, and activation of EphB2-MYC axis likely precedes BE development. Targeting EphB2/MYC could be a promising therapeutic strategy for this often refractory and aggressive cancer. [Display omitted] Esophageal adenocarcinoma is an aggressive cancer that develops from precursor Barrett's esophagus. We identify the EphB2 pathway as a potential promoter of Barrett's esophagus and associated cancer, uncovering new chemopreventive/therapeutic avenues. [ABSTRACT FROM AUTHOR]

This study was designed to compare the antitumor effects of anti-human MUC1 monoclonal antibody with those of anti-human CA199 monoclonal antibody coupled with drug-loaded polybutylcyanoacrylate nanoparticles on human pancreatic cancer cell lines and pancreatic cancer-bearing model animals and to screen more efficient targeting molecules. Gemcitabine-loaded nanospheres were prepared by emulsion polymerization (GEM-PBCA-NP), and then, anti-MUC1 monoclonal antibody was coupled with GEM-PBCA-NP (MUC1-GEM-PBCA-NP), and anti-human CA199 monoclonal antibody was coupled with GEM-PBCA-NP (CA199-GEM-PBCA-NP), using the chemical crosslinking method. The cell-killing rates were detected using MTT assay. The changes in the tumor cell cycle and apoptosis after treatment were detected using flow cytometry. Then, the subcutaneous planting method was adopted to establish an animal model of pancreatic cancer: two nanometer microspheres were injected into the body of nude mice via the tail vein; the tumor suppression effect was detected after treatment; then, the groups were compared. In vitro , the cell-killing rate of each experimental group was significantly different from that of the control group (P < 05). The MUC1-GEM-PBCA-NP group had a significantly higher cell-killing rate than the other groups (P < 05). The apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 05). In vivo , the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was 72.69% ± 4.29%, which was significantly higher than those of other groups (P < 0.05). The tumor inhibition rate of the CA199-GEM-PBCA-NP treatment group was 56.58% ± 5.11%, which was significantly higher than those of other control groups (P < 0.05). At the end of treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was 433.55 ± 12.49 mg, which was significantly lower than those of other groups (P < 0.05). Compared with CA199-GEM-PBCA-NP, MUC1-GEM-PBCA-NP is more effective in vitro and in vivo. MUC1 could be a target molecule in treating pancreatic cancer. [ABSTRACT FROM AUTHOR]

Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single‐domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion, and metastasis. Expressed nanobody demonstrated specificity only toward MUC1‐overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti‐MUC1 nanobody against MUC1‐positive human cancer cell lines ranged from 1.2 to 14.3 nm. Similar concentrations could also effectively induce apoptosis in MUC1‐positive cancer cells but not in normal cells or MUC1‐negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross‐reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3 µg nanobody per gram of body weight in tumor‐bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL‐1a, IL‐2, IL‐10, IL‐12, and IL‐17A pro‐inflammatory cytokines. Also, a significant decline in expression of Ki‐67, MMP9, and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti‐MUC1 nanobody‐treated mice. In conclusion, the anti‐MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion, and metastasis. [ABSTRACT FROM AUTHOR]

This study aims at investigating the potential role of MUC1 in CCR7-CCL21 axis-induced metastasis of tongue squamous cell carcinoma (TSCC). TSCC patients were selected for epidemiologic trends. The expression of CCR7 and MUC1 was detected via immunohistochemistry. SCC15 and CAL27 cells were induced by CCL21 and specific antibody to CCR7. Gene and protein expression was detected using qRT-PCR and western blotting. Migration and invasion capacities of TSCC cells were determined using wound healing and Transwell invasion assays. The male:female ratio of 78 patients was 1.6:1. Metastasis rate of cervical lymph nodes (CLNs) was 42.3%. CLN metastasis significantly correlated with T staging (P = 0.026), clinical staging (P = 0.024), and depth of invasion (DOI, P = 0.001). DOI significantly influenced CLN metastasis (P = 0.033, OR = 10.919) of TSCC, as did CCR7 (P = 0.041) and MUC1 (P = 0.026). The consistency of CCR7 and MUC1 expression was fairly good (Kappa = 0.683, P < 0.001). Reduced survival was significantly associated with higher expression of CCR7 (P = 0.039) and MUC1 (P = 0.030). CCL21 up-regulated MUC1 in SCC15 cells, which was inhibited when CCR7 was blocked. MUC1 positively correlated with TSCC cell migration and invasion. CCR7-CCL21 axis might promote CLN metastasis of TSCC by up-regulating MUC1. CCR7 and MUC1 show promise as potential biomarkers for TSCC treatment. [ABSTRACT FROM AUTHOR]

We previously demonstrated that a deficiency of natural antibodies against CD25, Mucin 1 (MUC1), and vascular endothelial growth factor receptor 1 (VEGFR1) could contribute to high risk of non‐small cell lung cancer (NSCLC). This study was designed to investigate whether natural IgG antibodies against POU domain class 5 transcription factor 1 (POU5F1), tumor necrosis factor‐α (TNF‐α), and the combination of CD25, VEGFR1, and MUC1 could play an anti‐tumorigenic role against developing NSCLC. An ELISA was developed in‐house to examine plasma IgG against peptide antigens derived from POU5F1, TNF‐α, and a combination of peptide antigens derived from CD25, MUC1, and VEGFR1 in 211 patients with NSCLC and 200 healthy controls. Mann–Whitney U test demonstrated that plasma IgG levels for the combination of peptide antigens derived from CD25, MUC1, and VEGFR1 were significantly lower in NSCLC patients than control subjects (Z = −12.978, P < 0.001) although plasma levels of IgG antibodies for POU5F1 and TNFα were not significantly changed. The in‐house ELISA made with the CD25‐MUC1‐VEGFR1 combination had a sensitivity of 49.6% against a specificity of 95% to detect early‐stage NSCLC. In conclusion, natural antibodies against the combination of CD25, VEGFR1, and MUC1 may be an effective biomarker for early diagnosis of NSCLC. [ABSTRACT FROM AUTHOR]

Enhanced glucose metabolism is one of the hallmarks of pancreatic cancer. MUC1, a transmembrane protein, is a global regulator of glucose metabolism and essential for progression of pancreatic cancer. To clarify the role of MUC1 in glucose metabolism, we knocked out MUC1 in Capan-1 and CFPAC-1 cells. MUC1 knockout (KO) cells uptook less glucose and secreted less lactate with a much lower proliferating rate. The mRNA level of key enzymes in glycolysis also decreased significantly in MUC1 KO cells. We also observed increased expression of breast cancer type 1 susceptibility protein (BRCA1) in MUC1 KO cells. Since BRCA1 has a strong inhibitory effect on glycolysis, we want to know whether the decreased glucose metabolism in MUC1 KO cells is due to increased BRCA1 expression. We treated wild type (WT) and MUC1 KO cells with BRCA1 inhibitor. BRCA1 inhibition significantly enhanced glucose uptake and lactate secretion in both WT and MUC1 KO cells. Expression of key enzymes in glycolysis also elevated after BRCA1 inhibition. Elevated glucose metabolism is known to facilitate cancer cells to gain chemoresistance. We treated MUC1 KO cells with gemcitabine and FOLFIRINOX in vitro and in vivo. The results showed that MUC1 KO sensitized pancreatic cancer cells to chemotherapy both in vitro and in vivo. In conclusion, we demonstrated that MUC1 promotes glycolysis through inhibiting BRCA1 expression. MUC1 may be a therapeutic target in pancreatic cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Airway mucins are the major constituents of mucus and one of the first lines of host defense against inhaled pathogens. However, aberrant expression of mucins is associated with mucus hypersecretion resulting in chronic nasal drainage, a common complaint from patients with chronic rhinosinusitis (CRS). Our goal in this systematic review was to determine (1) expression profiles, (2) regulatory mechanisms, and (3) the pathologic roles of mucins associated with CRS. Methods: MEDLINE, Cochrane Library, Embase, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies focused on the role of mucins in CRS. Quality was assessed using the Cochrane Risk of Bias tool. The full text articles selected were then categorized into 3 study groups: (1) clinical, (2) animal, and (3) in vitro cultures. Data regarding study design, population/setting, methods, and bias were extracted and synthesized. Results: Our initial search generated 392 titles/abstracts. After the primary review, 111 articles underwent secondary review. The final review included 53 articles, including 34 articles (64%) in the clinical study group, 3 articles (6%) in the animal study group, and 16 articles (30%) in the in vitro study group. In total, aberrant expression of 8 mucins—6 secreted-mucins (MUC2, -5AC, -5B, -6, -7, and -8) and 2 membrane-bound mucins (MUC1 and -4)—were identified in CRS tissues compared to healthy controls. Mucin expression was associated with bacterial sinusitis, inflammatory markers, and the response to steroid therapy in patients with CRS with nasal polyposis. Conclusion: There is a strong correlation between alterations in mucin expression profiles and CRS. This systematic review highlights the most recent literature on the role of mucins in CRS. The analysis of these studies is limited by the heterogeneity in study designs, relatively few numbers of clinical samples, and lack of mechanistic studies in animal models and in vitro cultures. [ABSTRACT FROM AUTHOR]

We report here numerous novel genes and multiple new signatures which robustly predict prostate cancer (PC) recurrence. We extracted 696 differentially expressed genes relative to a reported PC signature from the TCGA dataset (n = 492) and built a 15‐gene signature (SigMuc1NW) using Elastic‐net with 10‐fold cross‐validation through analyzing their expressions at 1.5 standard deviation/SD below and 2 SD above a population mean. SigMuc1NW predicts biochemical recurrence (BCR) following surgery with 56.4% sensitivity, 72.6% specificity, and 63.24 median months disease free (MMDF) (P = 1.12e‐12). The prediction accuracy is improved with the use of SigMuc1NW's cutpoint (P = 3e‐15) and is further enhanced (sensitivity 67%, specificity 75.7%, MMDF 45.2, P = 0) when all 15 genes were analyzed through their cutpoints instead of their SDs. These genes individually associate with BCR using either SD or cutpoint as the cutoff points. Eight of 15 genes are individual risk factors after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. Eleven of 15 genes are novel to PC. SigMuc1NW discriminates BCR with time‐dependent AUC (tAUC) values of 76.6% at 11.5 months (76.6%–11.5  m), 73.8%‐22.3  m, 78.5%‐32.1  m, and 76.4%–48.4  m. SigMuc1NW is correlated with adverse features of PC, high Gleason scores (odds ratio/OR 1.48, P < 2e‐16), and advanced tumor stages (OR 1.33, P = 4.37e‐13). SigMuc1NW remains an independent risk factor of BCR (HR 2.44, 95% CI 1.53–3.87, P = 1.62e‐4) after adjusting for age at diagnosis, Gleason score, surgical margin, and tumor stage. In an independent PC (MSKCC) cohort (n = 140), these 15 genes were altered in PC vs normal tissue, metastatic PCs vs primary PCs, and recurrent PCs vs nonrecurrent PCs. Importantly, a 10‐gene subsignature SigMuc1NW1 predicts BCR in MSKCC (P = 3.11e‐15) and TCGA (P = 3.13e‐12); SigMuc1NW1 discriminates BCR at 18.4  m with tAUC as 82.5%. Collectively, our analyses support SigMuc1NW as a novel and robust signature in predicting BCR of PC. [ABSTRACT FROM AUTHOR]

Previous work showed that miR-145 is downregulated in human serous epithelia ovarian carcinoma (SEOC) tissue and SKOV3 cells. However, the molecular mechanisms of miR-145 used to regulate ovarian proliferation and chemotherapy sensitivity remain to be determined. The present research demonstrate that miR-145 inhibit SKOV3 cells proliferation and promote chemotherapy sensitivity to paclitaxel according to MTT assay. MiR-145 inhibits Mucin1 (MUC1) post-transcriptional expression by binding to its 3'-untranslated region (UTR). The epithelial mesenchymal transition (EMT) marker E-cadherin (E-cad), which is downstream molecule of MUC1, is promoted by miR-145 overexpression. Furthermore, the E-cad protein level is inversely correlated with the expression of MUC1 in SKOV3 cells. It showed that promotion of E-cad signaling induced by miR-145 was released by MUC1 inhibition. Taken together, miR-145 serves as a tumor suppressor which can upregulate E-cad expression by targeting MUC1, leading to the inhibition of tumor proliferation and chemotherapy sensitivity. The miR-145 could be a rationale for therapeutic applications in ovarian carcinoma in the future. [ABSTRACT FROM AUTHOR]

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The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis. [ABSTRACT FROM AUTHOR]

Background A number of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) are resistant to oral corticosteroids. Mucin 1 (MUC1) shows anti-inflammatory properties, and its cytoplasmic tail (CT) interacts with transcription factors, facilitating their nuclear translocation. Because glucocorticoid receptor (GR) nuclear translocation is key to the anti-inflammatory effect of corticosteroids, we hypothesized that MUC1 is involved in the effectiveness of corticosteroids. Objective To analyze the role of MUC1 in corticosteroid effectiveness in different cohorts of patients with CRSwNP and elucidate the possible mechanisms involved. Methods Seventy-three patients with CRSwNP took oral corticosteroids for 15 days. Corticosteroid resistance was evaluated by nasal endoscopy. The expression of MUC1 and MUC1 CT was evaluated by real-time PCR, Western blotting, and immunohistochemistry. Beas-2B knockdown with RNA interference for MUC1 (siRNA-MUC1) was used to analyze the role of MUC1 in the anti-inflammatory effects of dexamethasone. Results Nineteen patients had nasal polyps that were resistant to oral corticosteroids (NP-CR). MUC1 expression was downregulated in these patients. Primary epithelial cells from patients with NP-CR were insensitive to the anti-inflammatory effects of dexamethasone. In siRNA-MUC1 Beas-2B, dexamethasone showed weaker anti-inflammatory effects, a reduced inhibition of phospho-extracellular-signal-regulated kinases 1/2, a less severe mitogen-activated protein kinase phosphatase 1 increase, and a reduced GR nuclear translocation. Immunoprecipitation experiments revealed that MUC1-CT and GRα form protein complexes and translocate to the nucleus in response to dexamethasone. MUC1-CT–GRα complex was downregulated in NP-CR tissue. Conclusion MUC1-CT participates in the corticosteroid response that mediates GRα nuclear translocation. The low expression of MUC1 in patients with CRSwNP may participate in corticosteroid resistance. [ABSTRACT FROM AUTHOR]

Background Mucoepidermoid carcinoma (MEC) is a malignant neoplasm that originates most commonly in the major and minor salivary glands. The aim of this study is to determine the relationship between mucin-1 (MUC1) expression and patient outcome based on a large number of cases. Patients and methods Surgical specimens from 357 patients with primary salivary gland MEC and 10 patients with normal salivary gland tissue were examined by immunohistochemistry. The relationship between MUC1 expression and the clinicopathological data and patient survival was analyzed. Results Results showed that MUC1 expression level was higher in MEC tissues than in paired normal tissues ( P = 0.001), and the expression level of MUC1 was significantly associated with gender ( P = 0.02), location ( P = 0.001), grade ( P = 0.001), stage ( P = 0.0018) and lymph node metastasis ( P = 0.001). In addition, increased expression of MUC1 was confirmed as a strong predictor of poor survival in salivary gland MEC (HR 2.175 [95% CI 1.263, 3.745]; P = 0.0051). Conclusion The findings indicate that an increased expression of MUC1 may be of great value in assessing the development and prognosis of salivary gland MEC, and could be used as a new molecule target to improve outcomes for these patients in the future. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effects of buzhong yiqi pills on the mucin 1 (MUC1), cythochrome C oxidase (COX), and nitric oxide synthase (NOS) expression and interaction in gastric tissue of diabetic rats. It says that the diabetic rat gastric mucosa damage model was intraperitoneally injected with streptozotocin (STZ) and orally administered to ethanol. The results of study is discussed.

Mucinous micropapillary carcinoma of the breast, also described as "pure mucinous carcinoma with micropapillary pattern," has recently come to attention as an unusual form of invasive breast cancer exhibiting dual mucinous and micropapillary differentiation. Despite increasing awareness of this morphologic variant, its clinical significance has not yet been elucidated. Here, we present 15 additional examples of these rare tumors to highlight some important differences between mucinous micropapillary carcinoma of the breast and ordinary pure mucinous carcinomas. The key features of mucinous micropapillary carcinoma of the breast included (a) largely or entirely mucinous appearance (N90% mucinous morphology), (b) distinctive micropapillary arrangement of the neoplastic cells, (c) intermediate to high nuclear grade, (d) "hobnail" cells, and (e) frequent psammomatous calcifications. In contrast to ordinary pure mucinous carcinomas, 20% of mucinous micropapillary carcinomas of the breast were characterized by human epidermal growth factor receptor 2 positivity, and 23% were p53 positive. More than half of mucinous micropapillary carcinomas of the breast (60%) demonstrated lymphovascular invasion, sometimes extensive. Synchronous axillary lymph node metastases were detected in 33% of patients and, on 2 occasions, involved more than 10 nodes. With a median follow-up of 4.5 years, we identified 1 patient (7%) with chest wall recurrence of mucinous micropapillary carcinoma of the breast after mastectomy. We conclude that mucinous micropapillary carcinomas of the breast constitute a clinically aggressive subset of mucin-producing breast carcinomas characterized by an increased capacity for lymphatic invasion and regional lymph node metastasis, reflective of their dual phenotype. Recognition of the morphologic and biologic heterogeneity within breast cancer subtypes should allow for a more accurate classification of the individual tumors and better patient stratification for treatment. [ABSTRACT FROM AUTHOR]

Abstract: Measuring CA15.3 serum levels in the early breast cancer setting is not recommended by current ASCO guidelines. In this large single center study, we assess the prognostic value of preoperative (n = 3746), postoperative (n = 4049) and change in (n = 3252) CA15.3, also across different breast cancer phenotypes. Preoperative, postoperative and change in CA15.3 were all significant (p = 0.0348, p < 0.0001, p < 0.0001 respectively in multivariate analysis) predictors of distant metastasis free survival. For breast cancer specific survival, only postoperative and change in CA15.3 were significant predictors (p < 0.0001 both). Multivariate prognostic models did not improve by incorporating information on preoperative CA15.3, but did improve when introducing information on postoperative CA15.3 for distant metastasis (p = 0.0365) and on change in CA15.3 for breast cancer specific survival (p = 0.0291). Change in CA15.3 impacts on prognosis (distant metastasis) differently in different breast cancer phenotypes. A decrease in CA15.3 may be informative of improved prognosis in basal like and HER2 like breast cancer. [Copyright &y& Elsevier]

Summary: Micropapillary carcinoma is a histologic pattern, rather than an independent entity, that has an aggressive clinical behavior regardless of location. Histologically, it is characterized by papillary cell groups in clear spaces. The micropapillary pattern in the thyroid gland has not been studied until recently but under other names such as hobnail features or oncocytic and, therefore, is poorly understood, and reported cases are few. We report the clinicopathologic features of 7 cases obtained from a cohort of 496 papillary thyroid carcinomas, which corresponds to a prevalence of 1.4%. The proportion of the micropapillary component accounted for between 5% and 20% of the tumors, was slightly more prevalent in men, correlated with the presence of lymphovascular permeation, and, in the survival analysis, showed lower survival (even at a short follow-up, 8.5 years) than conventional carcinoma without this component (P = .001); this is consistent with poor overall survival in the short term (2-5 years) reported for carcinomas with micropapillary pattern of other locations. We believe that owing to this difference in survival (>95% of patients with conventional papillary carcinoma are alive at 8.5 years versus 42% of those having at least 5% of micropapillary pattern), the micropapillary pattern should be correctly identified and stated in the pathology report when comprising at least 5% of the tumor. [Copyright &y& Elsevier]

Abstract: Objectives: Tumor-specific cytotoxic T lymphocytes can be efficiently activated in vivo by dendritic cell (DC)-based vaccination. This trial assessed the clinical efficacy and toxicity of DC-based immunotherapy in patients with advanced breast carcinoma. Methods: DC-based immunotherapy (DC vaccine alone or DC vaccine plus lymphokine-activated natural killer (NK) cell therapy) was administered to 26 patients with unresectable breast carcinoma refractory to standard treatment. After leukapheresis, DCs were generated from CD14+ monocytes by 6 day cultivation with GM-CSF and IL-4. DCs were then matured by OK-432 treatment and pulsed with cancer-associated antigens, such as WT1, MUC1, and HER2. DCs were administered 5–8 times intradermally at 14-day intervals. Results: Twenty-six patients with performance status (PS) of 0 (n = 4), 1 (n = 14), 2 (n = 4) and 3 (n = 4), and a median age of 55.5 years were eligible for this study. Of the 26 patients, DC vaccine was administered in combination with chemotherapy in 50%. Best response by RECIST, 1 patient showed a complete response (CR), 14 had partial response (PR), and 17 had stable disease (SD). The response ratio was 15.4％. None of the patients experienced adverse events of grade 2 or higher during the treatment period. The median overall survival (OS) time was 552.9 days (95% CI; 402.6–703.3 days). Log-rank test analysis demonstrated that the better PS groups (i.e., 0, 1) had significantly better survival times compared to those in poorer PS groups (i.e., 2, 3) (MST, 709.6 days, 95% CI, 502.2–917.0; vs. 200.4 days, 95% CI, 0–410.7; P < 0.001). Conclusion: DC vaccine-based immunotherapy demonstrates promising OS times and tolerable toxicities in the setting of breast carcinoma. A full risk/benefit analysis of DC-based vaccines in patients with metastatic breast carcinoma will be determined in a future phase II trial. [Copyright &y& Elsevier]

Summary: In this report, we present the clinicopathologic features of 13 cases of the invasive micropapillary variant of urothelial carcinoma. This is a rare and aggressive variant of bladder cancer recognized by the current World Health Organization classification of urologic tumors. The micropapillary component varied from 50% to 100% of the tumor specimen; in 10 cases, the micropapillary component composed greater than 70% of the tumor, with 5 cases showing pure micropapillary carcinoma. The architectural pattern of the tumor varied from solid expansile nests with slender papillae within tissue retraction spaces to pseudoglandular growth with prominent ring-like structures (2 cases, 15%) and invasive micropapillary carcinoma with squamous differentiation (2 cases, 15%); a streaking solid architectural pattern of micropapillary carcinoma was additionally present in 2 cases (15%). At histology, the individual tumor cells had abundant eosinophilic cytoplasm and nuclei with prominent nucleoli and irregular distribution of chromatin, and frequent mitotic figures. Most neoplastic cells had nuclei of low to intermediate nuclear grade with occasional nuclear pleomorphism. Eight mixed cases had concurrent conventional high-grade urothelial carcinoma with squamous or glandular differentiation in 3 and 1 case(s), respectively. All patients had advanced-stage cancer (>pT2), and 8 (62%) had lymph node metastasis. Immunohistochemical staining demonstrated that both micropapillary and associated conventional urothelial carcinomas were positive for MUC1 and 2, cytokeratin 7, PTEN, p53, and Ki-67. Her2Neu, uroplakin, cytokeratin 20, 34βE12, CA125, and p16 were positive in 4, 10, 8, 7, 3, and 3 cases, respectively. MUC5A, MUC6, and CDX2 were negative in all micropapillary cases. Follow-up information was available in all cases (range, 2-21 months; mean, 10 months). Eleven of patients died of disease from 2 to 14 months, and 2 patients were alive with disease at 14 and 21 months. Univariate statistical analysis showed survival differences between invasive micropapillary and conventional urothelial carcinomas (P < .0001). In summary, invasive micropapillary variant of urothelial carcinoma is an aggressive variant associated with poor prognosis that presents at an advanced clinical stage. The immunophenotype of invasive micropapillary carcinoma supports urothelial origin; the immunoreactivity to Her2Neu and PTEN might be relevant in terms of future targeting therapy. The morphologic diversity of micropapillary carcinoma may represent a diagnostic pitfall in limited samples, where its distinction from conventional urothelial carcinoma is critical for its clinical management. [Copyright &y& Elsevier]

The article discusses the chemoenzymatic synthesis of a mucine-1 (MUC1) glycopeptide carrying non-natural sialyl Thomsen Friedenreich-β Ο-glycan. The synthetic glocopeptide was released from the resin and the resulting benzylated glycopeptide was deprotected under conditions of low-acidity trifluoromethanesulfonic acid. Results show that enzymatic glycosylation was successful with both natural and non-natural Ο-glycans of the synthetic glycopeptide.

• Coefficient of kinetic friction (μ) of normal (4/4 RM-4) and tumor (CARM-L1 TG3) cell lines cultured on fibrine gel was measured. • Expression of MUC1 was not significantly different in the two cell lines. • μ was significantly higher in tumor cells than in normal cells. • Neuraminidase removed hystochemical stain of sialic acid from mesothelial glycocalyx, and increased μ. • Dexamethasone did not increase μ and MUC1 expression. To elucidate the role of sialomucin in friction reduction, we investigated the sliding friction of pleural mesothelial cells monolayers cultured on fibrine gel. These measurements were performed on normal (4/4 RM-4) and on tumor (CARM-L1 TG3) cell lines. The effect of treatment with neuraminidase, which removes sialic acid from sialomucin, and of dexamethasone, which has shown to increase sialomucin expression, were also assessed. Furthermore, the expression of the main form of cell-surface-associated mucin (MUC1) present in the mesothelium, was assessed by western blot and immunofluorescence, under different experimental conditions. Expression of MUC1 was not significantly different in the two cell lines. Moreover, dexamethasone did not increase the expression of MUC1. Coefficient of kinetic friction (μ) was significantly higher in tumor cells than in normal cells. Neuraminidase increased μ in both cell lines. These results suggest that sialomucin may play a role in reducing the friction of pleural mesothelial cells. [ABSTRACT FROM AUTHOR]

Abstract: MUC1 is a scaffolding protein harboring binding site for β-catenin in cytoplasmic domain. It might promote β-catenin nuclear translocation through integrating environmental cytokine signals, and coactivate β-catenin target genes which are related to tumor invasion, facilitating epithelial–mesenchymal transition in colorectal carcinoma. [Copyright &y& Elsevier]