Tissue Dysplasia Research Articles

Low expression of hsa_circ_0006633 in human gastric cancer and its clinical significances.

Circular RNAs are new type of endogenous RNAs, which play an important role in the regulation of gene expression and indicate a great capacity in clinical diagnosis and treatments of diseases. However, the role of circular RNAs in gastric cancer remains unknown. In this study, we chose hsa_circ_0006633 as the target circular RNA and measured its levels in human gastric cancer tissues, plasma, and gastric cell lines by real-time quantitative reverse transcription polymerase chain reaction. Hsa_circ_0006633 levels at multiple stages of gastric tumorigenesis were then explored, and its relationships with clinicopathological features were analyzed as well. We found that the expression levels of hsa_circ_0006633 in four gastric cancer cell lines, HGC-27, SGC-7901, MGC-803, and AGS, were downregulated than those in normal gastric mucosal epithelial cell line GES-1. Then, we further detected that it was downregulated in 79.2% (76/96) gastric cancer tissues compared with the adjacent non-tumorous tissues. The lower expression of hsa_circ_0006633 was associated with cancer distal metastasis ( p = 0.037) and tissue carcinoembryonic antigen level ( p = 0.041). In addition, hsa_circ_0006633 expression was significantly decreased in gastritis and dysplasia tissues comparing with the healthy control. Moreover, plasma hsa_circ_0006633 levels were significantly increased in gastric cancer compared with healthy control. Our data imply that hsa_circ_0006633 may play an important role in gastric carcinogenesis and is also a potential biomarker for screening gastric cancer.

Risk factors, predictors and contemporary diagnostics of bronchopulmonary dysplasia

Improving of resuscitation and intensive care of premature babies allowed their survival. Bronchopulmonary dysplasia (BPD) is the significant complication of low-birth newborns. Identification of early predictors of disease can optimize of treatment and decrease of quantity of appearance and severity of BPD. Quantity of BPD is 5-97%. The significant predictors from hereditary and genetic factors are family bronchopulmonary pathology, dysplasia of connective tissue, gene polymorphism of VEGF, EPNX-113 Hiss, Nos3-786C, GCLC, 58 Т/С sod2, minore allele - 460 of T-gene (VEGF); from clinical and immunological factors - lung immaturity, alveolarization and vascularization disorders, hemodynamically significant ductus arteriosus; from biochemical factors - hyperoxy, lipid peroxidation and decreasing of antiperoxidation, disorder of angiotensin-1/endostatin; from therapeutic factors - overexertion of lungs during ventilation, avoiding of antiperoxid protection, insufficiency of nutrition. Contemporary methods of BPD diagnostic are clinical data (oxygen dependence at 28 days after birth), X-ray sings, identified by X-ray examination and tomography and bronchophonography. More of identified factors and predictors of BPD are difficult for examinations, haven’t 100% result or low predictive power, that is why further study is needed.

Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma.

Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor-associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r2 = 0.109; p < 0.0001, r2 = 0.64; and p < 0.001, r2 = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest that tumor necrosis factor receptor-associated factor 1 has potential direct/indirect regulations with the cancer stem cell markers in oral squamous cell carcinoma, which may help in further analysis of the cancer stem cell characteristics.

Hypermethylation of IFN-γ in oral cancer tissues.

The study aimed to evaluate the methylation pattern of the interferon-gamma (IFN-γ) gene in oral cancer tissues compared with normal and benign oral disease tissues. The oral tissues were gained from the patients of 85 cases of oral squamous cell carcinoma (OSCC), 47 cases of oral dysplastic lesions, and 53 normal biopsies. IFN -γ methylation in oral tissues was verified through methylation-specific polymerase chain reaction (PCR) and DNA sequencing analyses, and the expression levels of IFN-γ messenger RNA (mRNA) and protein were detected using real-time reverse transcription (RT)-PCR and enzyme-linked immunosorbent assays, respectively. IFN-γ was localized in macrophages from oral tissues and detected via immunostaining. IFN-γ mRNA and protein expression levels were evidently decreased in oral cancer tissues, whereas the IFN-γ methylation rate was significantly higher in malignant tumors than in benign and normal tissues (normal, 22.6%; benign, 38.3%; and cancer, 55.3%; P<0.05). Furthermore, the expression of IFN-γ mRNA was significantly downregulated in oral tumors with methylation compared with tumors without methylation, as determined by real-time RT-PCR (4.76-fold difference; P<0.05). Likewise, mRNA expression was downregulated by 6.79-fold in oral epithelial dysplasia tissues with methylation compared with those without methylation (P<0.01). Co-immunostaining to detect MAC2 and IFN-γ demonstrated that macrophages comprised the main source of IFN-γ in oral tissues. IFN-γ methylation demonstrated a significant association with the clinical stage, histopathology grade, and primary tumor. Aberrant IFN-γ promoter methylation may be involved in the process of tumorigenesis of oral cancer. IFN-γ hypermethylation during the process of oral carcinogenesis could be useful for the clinical diagnosis and treatment for OSCC.

Генетические основы патобиохимических особенностей соединительной ткани больных с пролапсом гениталий

Purpose: to study the molecular biological basis of genital prolapse, its determination by the carrier of polymorphisms of laminin, collagen, estrogen receptor and vascular endothelial growth factor. Materials and methods: 178 women aged 35-65 years were examined, 134 of them with relapses of prolapse genital (PG) after hysterectomy with vaginal access due to complete and incomplete prolapse of the uterus and vaginal walls were randomized into groups: 1 - with manifestations of undifferentiated connective dysplasia tissue (DST), 11.7 points on average (n=86); 2 - without signs of DST (n=48). The control group 3 consisted of healthy women without signs of PG (n=44). The morphological method of investigation along with the immunohistochemical method was used to evaluate the biopsy specimens of the uterosacral ligaments (USL) and round ligaments of the uterus (RLU), the genotyping by polymerase chain reaction of polymorphisms LAMC1 3054 C>T, COL3A1 2092 (2209) G>A, ESR1 351 G>A [XbaI], VEGFA 634 G>C with isolation of DNA samples from whole blood. Results: morphological features of the structural components of the USL and RLU were realized in the predominance of excessive fibrosis of the connective tissue on the background of disunity and loosening of collagen fibers and myocyte dystrophy. Expressed dysplastic changes with loss of elasticity of fibers due to increased fragmentation of elastin, excessive synthesis of the least strong type III collagen in comparison with type I, perivascular edema were traced in the group with signs of DST (in 65% of women). The decrease in tissue strength in the imbalance of synthesis and degradation of collagens in patients with PG was correlated with the excess production of type III protein - high in USL and moderate - in RLU. Healthy women were distinguished by the prevalence of type I collagen (5.5 and 4.2 points respectively) - one and a half times more than in pelvic descent (3.2 and 2.7 points respectively). The increased degradation of elastic fibers in PG determined the fragmentarity of their distribution in the ligamentous apparatus of the uterus in comparison with the uniform one - along the collagen fibers, in the extracellular matrix and fibroblasts, the walls of the arterioles of the USL and RLU in healthy women. The genetic determinateness of molecular-biological features of connective tissue structures with PG is determined, which allows to predict the risk of the disease development at the preclinical stage. The carriage of risky alleles of the genes COL3A1 2092 (2209) G>A (rs1800255) (45.8% vs 29.5%) in the presence of DST manifestations indicated associativity with PG. The frequency of the allele GC of the VEGFA gene with PG was equally increased: in the absence of signs of DST - by one and a half times (59.3% vs 36.4%, p=0.002, OR=9.9, 95% CI 1.6-7.6), in the presence of collagenopathies - in two (35.4% versus 15.9%, p=0.01, OR=2.9, 95% CI, 1.1-6.9) with a comparable occurrence of heterozygotes (36.9% on average). The absence of associative links was established for laminin LAMC1 (connective tissue) (50% versus 31.8%) and estrogen receptor ESR1 -351 G> A [XbaI] (43.4%). Representatives with collagenopathies distinguished the high carrier burden of the mutant polymorphism rs3918242 - twice as much compared to the control group (35.4% vs 15.9%, p=0.01, OR=2.9, 95% CI 1.1-6.9) with a comparable occurrence of heterozygotes (36.9% on average). The conclusion. The determinism of pathobiochemical features of connective tissue is revealed - the imbalance of synthesis and degradation of its components, the formation of an abnormal structure of fibers and the expressed polymorphism of polymorphisms of genes that control the safety of tissue architectonics of the pelvic ligaments. Expansion of PG prediction capabilities is most likely in the presence of signs of DST predetermining the systemic nature of its lesion and variety of symptoms, with a particular manifestation in the form of pelvic floor insufficiency in the presence of risky polymorphisms of the genes LAMC, COL3A1 and VEGFA. Determination of genes predisposing to PG allows us to formulate the concept of its pathogenesis, with the identification of risk groups not only of development, but also the relapse of the disease after surgery, by choosing the most optimal method of surgical correction.

Факторы риска сосудистой патологии головного мозга при наследственной дисплазии соединительной ткани

Факторы риска сосудистой патологии головного мозга при наследственной дисплазии соединительной ткани

Mast cells and angiogenesis in malignant and premalignant oral lesions: An immunohistochemical study.

Introduction and Objectives:Angiogenesis is a complex event facilitated by angiogenic factors released from neoplastic and host immune cells. Among host immune cells, mast cells (MCs) may have greater significance in tumor progression through angiogenesis. The objectives of the study were to evaluate and correlate mast cell density (MCD) and microvessel density (MVD) in normal gingival tissue, leukoplakia with and without dysplasia and oral squamous cell carcinoma (OSCC) cases.Materials and Methods:Among eighty selected cases, twenty were of normal gingiva, twenty each of leukoplakia without and with dysplasia and twenty of OSCC. The slides were stained with CD34 and counterstained with 0.1% toluidine blue, followed by quantification of MCD and MVD per high-power field (×40) using Image-Pro Express software.Statistical Analysis:Chi-square test and correlation coefficient were used for statistical analysis.Observation and Results:A statistically significant difference in the values of MVD and MCD between normal gingival tissue, leukoplakia with and without dysplasia and OSCC (P = 0.000) was observed. MVD and MCD showed a positive correlation between the study groups.Conclusion:MVD and MCD increased significantly in cases of OSCC as compared to leukoplakia with and without dysplasia and normal gingival tissue. It was concluded that MCs may play a significant role in angiogenesis by releasing pro-angiogenic and angiogenic factors which may in turn favor the progression of premalignant lesion to a malignant one.

Значення гетерохроматину і поліморфних варіантів генів фолатного циклу у жінок з репродуктивними втратами

The article presents data from surveys of women of losses of pregnancy (LP) in history, conducted within the medical genetic counseling, given the urgency of specifying genetic factors that actually are in causal connection with the LP specification clinical effects of epigenetic variability. The objective: to clarify the meaning of the changes in women heterochromatin (chromosomal polymorphism) and polymorphic variants of genes folat cycle enzymes as potential risk factors and pathogenic primordial LP. Patients and methods. The study involved two groups of women: I - 154 observations with complicated obstetric history in LP and II - 32 healthy women with uncomplicated reproductive history, held preconception planning to prevent pregnancy. Studied genealogical history, especially of internal organs, genitalia. Special studies included cytogenetic analysis, identification of gene polymorphisms system folat cycle methylentetrahydrofolate reductase [MTHFR] (C677T, A1298C, G1793A); methionine synthase reductase [MTRR] (A66G). Results. Women with a history of LP in 36.4% identified chromosome polymorphisms (SNPs extreme variants of chromosome polymorphism) on the background of various risk alleles of polymorphic variants of genes folat cycle; 7.1% of them is a polymorphism of the 21st chromosome. These genetic features are interpreted as a significant risk factor for LP as grounds for targeted in-depth medical and genetic examination. Prevalence among women with a history of PL undifferentiated forms cjnnective tissue and mesoderm dysplasia, benign tumors and «precancerous» states, as well as the prevalence of cardiovascular and psycho-neurological disease in pedigree suggests pathogenetic link these phenomena, the role of chromosomal polymorphism and polymorphic variants of genes of pathogenic folat cycle as primordial. Conclusion. The data on the place and role of heterochromatin and gene polymorphisms folat cycle in the origin LP should be mandatory option when examining women within the medical genetic counseling. Key words: pregnancy, reproductive losses, chromosomal instability, folat cycle genes, ancestry.

A novel morphological approach to gonads in disorders of sex development

AbstractDisorders of sex development are defined as congenital conditions with discordance between the phenotype, the genotype, the karyotype, and the hormonal profile. The disorders of sex development consensus classification established in 2005 are mainly based on chromosomal and biological data. However, histological anomalies are not considered. The aims of this study were to define the specific pathological features of gonads in various groups of disorders of sex development in order to clarify the nosology of histological findings and to evaluate the tumor risk in case of a conservative approach. One hundred and seventy-five samples from 86 patients with disorders of sex development were analyzed following a strict histological reading protocol. The term ‘gonadal dysgenesis' for the histological analysis was found confusing and therefore excluded. The concept of ‘dysplasia' was subsequently introduced in order to describe the architectural disorganization of the gonad (various degrees of irregular seminiferous tubules, thin albuginea, fibrous interstitium). Five histological types were identified: normal gonad, hypoplastic testis, dysplastic testis, streak gonad, and ovotestis. The analysis showed an association between undifferentiated gonadal tissue, a potential precursor of gonadoblastoma, and dysplasia. Dysplasia and undifferentiated gonadal tissue were only encountered in cases of genetic or chromosomal abnormality (‘dysgenesis' groups in the disorders of sex development consensus classification). ‘Dysgenetic testes', related to an embryonic malformation of the gonad, have variable histological presentations, from normal to streak. Conversely, gonads associated with hormonal deficiencies always display a normal architecture. A loss of expression of AMH and α-inhibin was identified in dysplastic areas. Foci of abnormal expression of the CD117 and OCT4 immature germ cells markers in dysplasia and undifferentiated gonadal tissue were associated with an increased risk of neoplasia. This morphological analysis aims at clarifying the histological classification and gives an indication of tumor risk of gonads in disorders of sex development.

The characteristics of magnesium homeostasis and remodeling of heart in patients with ischemia of myocardium against the background of non-differentiated dysplasia of connective tissue

The study was carried out to evaluate dynamics of level of magnesium of blood serum and structural functional parameters of heart in patients with acute myocardium infarction developed against the background of non-differentiated dysplasia of connective tissue. The study included 90 patients with myocardium infarction with Q wave and with and without nondifferentiated dysplasia of connective tissue. The control group consisted of healthy persons and comparison group included patients with non-differentiated dysplasia of connective tissue without cardiovascular pathology. The clinical and phenotype examination including echocardiography testing of heart, detection of level of magnesium in blood serum in dynamics of myocardium infarction course were implemented. In patients with myocardium infarction, independently of occurrence of non-differentiated dysplasia of connective tissue during the first day of study decreasing of level of magnesium in blood serum was observed. In the group of patients with myocardium infarction, and non-differentiated dysplasia of connective tissue, up to twenty-eighth day, reliable decreasing of magnesium occurred as compared with control group and comparison group. In group of patients with myocardium infarction and non-differentiated dysplasia of connective tissue expressed increase of size of cavity of left ventricle was established including decreasing of its pumping function in combination with tendency to less expressed increasing of index of myocardium mass of left ventricle as compared with patients with myocardium infarction and without non-differentiated dysplasia of connective tissue. In patients with myocardium infarction occurring against the background of non-differentiated dysplasia of connective tissue hypomagnesemia is associated with development of desadaptive alternative of post-infarction remodeling of heart characterized by prevalence of processes of dilatation of cavity of left ventricle with decreasing of contractive capacity over processes of hypertrophy of myocardium.

Optical redox ratio differentiates early tissue transformations in DMBA-induced hamster oral carcinogenesis based on autofluorescence spectroscopy coupled with multivariate analysis

Fluorescence intensity measurements have the potential to facilitate the diagnoses of many pathological conditions. The changes in fluorescence intensity may be influenced by factors such as tissue architectures, endogenous fluorophores, cellular metabolism and light penetration depth in tissue. Two of the most diagnostically important endogenous fluorophores are reduced nicotinamide dinucleotide (NADH) and flavin adenine dinucleotide (FAD), which can be used to monitor dramatic metabolic changes in cells and tissues. The goal of this study is to investigate changes in the endogenous fluorophore emission and to quantify metabolic changes in the redox state of various tissue transformation conditions with respect to control tissues in dimethyl benz[a] anthracene (DMBA)-induced hamster oral carcinogenesis for measuring emission spectrum at 320 nm excitation. In the present study, collagen, NADH and FAD emission of well-differentiated squamous cell carcinoma (WDSCC) showed decreased intensity at ~385 nm, ~450 nm and ~520 nm compared to hyperplasia, dysplasia and control tissues. Furthermore, a significant decrease in the optical redox ratio is observed in WDSCC tissues, which indicates an increased metabolic activity compared to the control tissues. Moreover, the principal component linear discriminant analysis (PC-LDA) algorithm together with the leave-one-out cross-validation (LOOCV) method yield an overall diagnostic sensitivity of 77.7% and a specificity of 88.8% in the classification of control, hyperplasia, dysplasia and WDSCC tissues, respectively. The results from this study demonstrated that fluorescence-based tissue analysis combined with PC-LDA has tremendous potential for the effective discrimination of control from neoplastic tissues; furthermore it also detects early neoplastic changes prior to definite morphologic alteration.

Морфоклінічні та променеві аспекти діагностики бронхолегеневих захворювань та їх ускладнень у дітей з дисплазією сполучної тканини (огляд літератури)

Морфоклінічні та променеві аспекти діагностики бронхолегеневих захворювань та їх ускладнень у дітей з дисплазією сполучної тканини (огляд літератури)

The Downregulation of MicroRNA-10b and its Role in Cervical Cancer.

It has been demonstrated that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety of cancers. Our previous work suggested that miR-10a/b functioned as a tumor suppressor in gastric cancer, and miR-10b was also reported to be significantly downregulated in advanced stage cervical cancer tissues. However, the aberrant expression of miR-10b in cervical cancer and its possible role in cervical carcinogenesis was largely unknown. In this study, we investigated the expression of miR-10b in cervical cancer tissues, carcinoma in situ tissues, mild dysplasia, moderate dysplasia, severe dysplasia tissues, and normal controls. We found that miR-10b was significantly downregulated during cervical cancer progression, and the lower level of miR-10b in cervical cancer was significantly associated with a more aggressive tumor phenotype. Moreover, overexpression of miR-10b in cervical cancer cells could inhibit the cell proliferation and invasion, and the further mechanism study suggested that its role was possibly through directly targeting HOXA1. These results suggested that the downregulation of miR-10b and the resulting elevated HOXA1 level in cervical cancer tissues might play critical roles in cervical cancer progression.

Cyclooxygenase-2 expression and its association with vascular endothelial growth factor, microvessel density and clinicopathologic characteristics of colorectal carcinoma

The aim of this study was to investigate the expression of cyclooxygenase type-2 (COX-2) and its association with angiogenesis and clinicopathologic characteristics of colorectal carcinoma (CRC). COX-2 expression was detected by means of immunohistochemistry in a series of human tissue samples with CRC (n = 120), dysplasia tissue closely adjacent to carcinomas (n = 40) and normal colorectal mucosa (n = 40), and their expressions association with vascular endothelial growth factor (VEGF), CD31-labeled micorvessel density(MVD) in CRC and other clinicopathologic characteristics were investigated. The expression of COX-2 in CRC tissues (78.3%) was obviously higher than that in adjacent tissue and normal mucosal tissue (p&lt;0.01). COX-2 expression was correlated significantly with the grading, advanced cancer, Dukes stage and lymph node metastasis, distant metastasis and VEGF (p&lt;0.05). Our result demonstrates that COX-2 expression was significantly higher in earlier stages of CRC. It can be suggested that COX-2 expression may be important in the initial development of CRC. The findings of the present study suggest that COX-2 overexpression in CRC may be considered as a negative prognostic marker.

Язвенный дефект, как одно из проявлений приобретённой дисплазии соединительной ткани

Язвенный дефект, как одно из проявлений приобретённой дисплазии соединительной ткани

CLINICAL AND GENETIC ASPECTS OF ABNORMAL TORTUOSITY OF PRECEREBRAL ARTERIES IN ISCHEMIC STROKE

Background: Inherited connective tissue pathology is the most frequent genetic abnormality. Weakness of connective tissue in this group of disorders is manifested not only by excessive joint mobility, but also by abnormalities in other organs and systems, including vessels. In inherited connective tissue disorders brain artery aneurysms and abnormal vascular tortuosity is found that can be a risk factor for stroke. Aim: To study frequency of abnormal tortuosities of brachiocephalic vessels in post-ischemic stroke patients, as well as efficacy of secondary stroke prevention in such patients. Materials and methods: One hundred and seventy two adult patients with ischemic stroke were examined. Neurological deficiency was assessed with the National Institute of Health Stroke Scale (NIHSS) and with the modified Rankin scale. Abnormalities of precerebral arteries were found by ultrasound dopplerography and duplex scanning. To diagnose any abnormalities of connective tissue, clinical and genetic analysis, dermatoglyphic assessment and scoring of excessive joint mobility (Beyton scale) were used. Results: Abnormal tortuosity of precerebral arteries is found in 47% of patients with ischemic stroke. The screening performed in 25 of such patients showed connective tissue disorders in one third of them (in 2 patients, Ehlers-Danlos syndrome, in 2 patients, connective tissue dysplasia, in 4 patients, mild symptoms of abnormal connective tissue, such as excessive joint mobility scoring to 1–2). In patients without inherited syndromes, some dermatoglyphic traits were found, i.e., distal shift of the axial palmar triradius, higher frequency of patterns on the skin of the thenar, lower pattern frequency on the skin of the hypothenar, higher frequency of simple digital patterns (A and T), lower frequency of complex patterns, such as whorls (W), lower palmar and digital ridgecounts. The results of secondary stroke prevention with antiplatelet agents, antihypertensives and cholesterol-lowering agents depended on patient compliance to medical recommendations. The odds ratio for a repeated stroke in the groups who were regularly taking these agents, compared to the groups who were not, was 0.116 for treatment with antiplatelet agents (p < 0.05) and 0.043 for antihypertensive therapy (p < 0.005). Conclusion: Dysplasia of connective tissue can lead to formation of tortuous precerebral arteries and become an additional risk factor for strokes. Conventional antiplatelet, antihypertensive and cholesterol-lowering prophylaxis is effective in patients with tortuous precerebral arteries, but its results depend on patient compliance.

Expression of SRSF3 is Correlated with Carcinogenesis and Progression of Oral Squamous Cell Carcinoma.

Objective: Oral squamous cell carcinoma (OSCC) is the most common malignancy of head and neck with high mortality rates. The mechanisms of initiation and development of OSCC remain largely unknown. Dysregulated alternative splicing of pre-mRNA has been associated with OSCC. Splicing factor SRSF3 is a proto-oncogene and overexpressed in multiple cancers. The aim of this study was to uncover the relationship between SRSF3 and carcinogenesis and progression of oral squamous cell carcinoma.Design and Methods: The expression of SRSF3 in oral normal, dysplasia, or carcinoma tissues was analyzed by immunohistochemistry. The expression levels of EMT-related genes were quantified by real-time quantitative RT-PCR. The expression of SRSF3 in DMBA treated primary cultured oral epithelial cells were analyzed by western blot.Result: SRSF3 is overexpressed in oral cancer and moderate or severe dysplasia tissues. Patients with high grade cancer or lymphatic metastasis showed up-regulated expression of SRSF3. Knockdown of SRSF3 repressed the expression of Snail and N-cadherin in vitro. Carcinogen DMBA treated primary cultured oral epithelial cells showed significantly increased SRSF3 level than in control cells.Conclusion: Our results suggested that SRSF3 is associated with the initiation and development of OSCC and may be a biomarker and therapeutic target of OSCC.

Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients.

The nuclear localization of Drosha is critical for its function as a microRNA maturation regulator. Dephosphorylation of Drosha at serine 300 and serine 302 disrupts its nuclear localization, and aberrant distribution of Drosha has been detected in some tumors. The purpose of the present study was to assess cytoplasmic/nuclear Drosha expression in gastric cancer carcinogenesis and progression. Drosha expression and its subcellular location was investigated by immunohistochemical staining of a set of tissue microarrays composed of normal adjacent tissues (374), chronic gastritis (137), precancerous lesions (94), and gastric adenocarcinoma (829) samples, and in gastric cancer cell lines with varying differentiation by immunofluorescence and western blot assay. Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P < 0.001), tumor stage (P = 0.018), and distant metastasis (P = 0.026). Aberrant high levels of cytoplasmic Drosha were apparent in intestinal metaplasia and dysplasia tissues. The levels of nuclear Drosha were sharply decreased in chronic gastritis and maintained through precancerous lesions to gastric cancer. High levels of cytoplasmic Drosha predicted longer survival (LR = 7.088, P = 0.008) in gastric cancer patients. Our data provide novel insights into gastric cancer that cytoplasmic Drosha potentially plays a role in preventing carcinogenesis and tumor progression, and may be an independent predictor of patient outcome.

Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery

Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics.

Features of the blood circulation in the uterus and ovaries of women with dysplasia of connective muscular tissue of the pelvic floor

Features of the blood circulation in the uterus and ovaries of women with dysplasia of connective muscular tissue of the pelvic floor