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N J Agnantis

Publications and source records attributed to N J Agnantis.

At least 37 records · Page 2Linked to original sources

p63 expression in benign and malignant breast lesions.

The p63 gene encodes six protein isoforms. The transactivating isoforms have similar actions with p53, while the N-isoforms inhibit transcription activation by p53 and transactivating isoforms. p63 is expressed in stratified epithelia and in basal cells of the prostate and salivary glands. In mammary epithelium p63 has been shown to be expressed only in the myoepithelial layer. In the present study we investigated the immunohistochemical expression of p63, in benign and malignant breast lesions, and compared it with known myoepithelial cell markers. Our material consisted of 140 benign and 126 malignant breast lesions. We used the antibodies anti-p63, anti-alpha-smooth muscle actin, anti-S-100 protein and anti-cytokeratin 14. In all benign lesions, p63 immunoreactivity was noted in the myoepithelial cell layer surrounding the luminal epithelial cells. A less continuous peripheral rim of myoepithelial cells was also highlighted with p63-staining in all situ carcinomas. All invasive breast carcinomas were devoided of peripheral p63 staining. Interestingly, strong nuclear p63 immunoreactivity was noted in a small fraction (5-15%) of epithelial cells in all cases of papillomatosis, in 62.5% of in situ ductal papillary-type carcinomas and in 33.3% of invasive papillary carcinomas. Comparable staining was observed with S-100. The stromal cells were unreactive to p63. Our findings suggest that p63 is a sensitive and specific myoepithelial marker, and may be included in immunohistochemical panels aiming to identify myoepithelial cells in problematic breast lesions. Regarding papillary neoplasms, it is possible that tumor cells acquire and exhibit at least in part a myoepithelial differentiation program.

Actins↗

Immunohistochemical expression of superoxide dismutase (MnSOD) anti-oxidant enzyme in invasive breast carcinoma.

The most important cellular protective mechanisms against oxidative stress are antioxidant enzymes. Their action is based on decomposal of reactive oxygen species (ROS) and their transformation to H2O2. Within the mitochondria manganese superoxide dismutase (MnSOD) affords the major defense against ROS. In this study we investigated tissue sections from 101 breast carcinomas for the immunohistochemical expression of MnSOD protein and these results were assessed in relation to various clinicopathological parameters, in order to clarify the prognostic value of this enzyme. The possible relationship to hormone receptor content, anti-apoptotic protein bcl-2, p53 and cell proliferation was also estimated. High expression levels were observed, as 79/101 (78,2%) cases expressed strong immunoreactivity. In this study MnSOD increased in a direct relationship with tumor grade and is therefore inversely correlated with differentiation (p=0.0004). Furthermore, there was a strong positive correlation between MnSOD expression and p53 protein immunoreactivity (p=0.0029). The prognostic impact of MnSOD expression in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis was statistically not significant. These results indicate that neoplastic cells in breast carcinomas retain their capability to produce MnSOD and thus protected from the possible cellular damage provoked by reactive oxygen species. In addition, MnSOD content varies according to the degree of differentiation of breast carcinoma.

Age Distribution↗

Estrogen receptor beta (ERbeta) expression in breast carcinomas is not correlated with estrogen receptor alpha (ERalpha) and prognosis: the Greek experience.

Estrogen receptors (ER) are members of the nuclear receptor superfamily of ligand-activated transcription factors and mediate the effects of estrogen on target tissues. ERalpha was the first estrogen receptor to be characterized, and ERbeta was identified ten years later. The role of ERbeta in breast cancer pathobiology is largely unknown because specific antibodies have not been available until recently. The purpose of this study was to explore the expression of ERbeta in breast neoplasms and to correlate it with ERalpha and prognosis. ERa and ERbeta expression was monitored immunohistochemically in 59 breast carcinomas. We found no correlation between ERalpha and ERbeta expression, between ERbeta expression and the known prognostic indicators such as tumor size, grade or lymph node status, or between ERbeta expression and survival. Our findings contribute to the better understanding of the role of ERbeta in breast cancer.

Adult↗

Aggressive angiomyxoma of the vagina: a case report and review of the literature.

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor of the lower pelvis and genital region, characterized by local infiltration and frequent, even multiple recurrences. In the present paper a case of a small-sized AA of the vagina, in a 55-year-old woman is reported. We describe the histological appearance and the immunohistochemical phenotype of this tumor and discuss its differential diagnosis from other mesenchymal lesions occurring in the pelvic and genital region. Furthermore, we attempt to enlighten the possible mechanisms that govern the pathogenesis and the biological behavior of this "mysterious" neoplasm.

Biopsy, Needle↗

Expression patterns of cyclins D1, E in laryngeal epithelial lesions: correlation with other cell cycle regulators (p53, pRb, Ki-67 and PCNA) and clinicopathological features.

The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.

Adult↗

Angiotropic large cell lymphoma.

A 67 year old man developed "status epilepticus" and died with acute respiratory failure. An autopsy and concomitant histological examination, revealed intravascular infiltrate of lymphoid cells throughout the body. Immunohistochemical studies showed intense positive staining for leukocyte common antigen (LCA), L26 and CD20 and negative staining for Factor VIII- related antigen, and CD5, demonstrated that the neoplastic cells were of B-cell lineage.

Aged↗

The role of tumor markers in non-palpable breast cancers.

Screening mammography and clinical breast examination are the best tools available for the diagnosis of breast carcinomas in asymptomatic women. Many studies have attempted to determine the pathological and biological characteristic findings in screening-detected cancers. Tumor size, histologic type, cytological grading and lymph node status have an important role in estimating the biological profile of non-palpable breast cancers. Tissue tumor markers, such as proliferation markers, hormone receptors, c-erbB-2 and p53 oncoproteins, bcl-2 gene and angiogenesis-related markers do not seem to distinguish mammographically detected tumors from clinically presented cancers. Further studies are needed to assess the prognostic role of certain biological factors in well-designed clinical studies along with long follow-up of screened patients.

Biomarkers, Tumor↗

Electron immunocytochemical demonstration of serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon in mirror biopsies from primary colorectal adenocarcinoma.

The aim of this study was to investigate the ultrastructural appearance of mirror biopsies from primary colorectal adenocarcinomas combined with serotonin, vasoactive intestinal polypeptide, bombesin, somatostatin and glucagon expression in order to clarify the histology and immunology of these tissues compared with colorectal adenocarcinomas. The investigation was carried out in 90 cases of mirror biopsies by electron microscope immunocytochemistry. The ultrastructural study revealed that some cases (30%) of mirror biopsies were characterized by the presence of intracellular changes compared to normal tissues. The most significant of them were the presence of swollen abnormal mitochondria and the increased number of the secretory cells. The above enzymic and secretory changes were confirmed by electron immunogold results. Bombesin and VIP appeared to be located in enterochromaffin-like (ECL) endocrine cells primarily responsible for the production of serotonin. Somatostatin was located in D cells while we found numerous glucagon (EG) immunoreactive cells. In conclusion, low somatostatin expression, high glucagon and serotonin expression and the ectopic secretion of VIP and bombesin neuropeptides in mirror biopsies indicate the preneoplastic nature of these tissues and may be useful for the optimal treatment of patients with colorectal adenocarcinoma.

Adenocarcinoma↗

Expression of the cell-cycle regulatory proteins (cyclins D1 and E) in endometrial carcinomas: correlations with hormone receptor status, proliferating indices, tumor suppressor gene products (p53, pRb), and clinicopathological parameters.

PURPOSE OF INVESTIGATION: This study aimed to investigate the immunohistochemical expression of cyclins D1 and E in normal, hyperplastic and neoplastic endometrium, and their correlation with proliferative activity and clinicopathological features. METHODS: We carried out immunohistochemical techniques on archived material of formalin-fixed paraffin-embedded tissues using the antibodies against the cyclins D1 and E, PR-ER, p53, Ki67 (MIB1) and pRb with the streptavidin-biotin-peroxidase method in a total of 20 cases of normal endometrium, 32 cases of hyperplastic endometrium and 66 cases of endometrial carcinomas. RESULTS: Cyclin D1 and E immunoreactivity was observed in the nuclei of tumour cells in 18.2% and 39.1%, respectively, of the cases of endometrial carcinomas. Cyclin D1 labelling index was not significantly correlated with any of the clinicopathologic parameters examined. However, there was a significant correlation between the cyclin E labelling index and histological grade of carcinoma (p = 0.00096), which increased significantly with histological grades of malignancy. We also detected a significant correlation between cyclin E and PCNA (p < 0.0001) as well as with the tumor suppressor genes p53 and pRb (p = 0.052 and 0.0002, respectively) in endometrioid endometrial carcinoma. CONCLUSION: Our results indicate that cyclin E overexpression may be involved in the development and/or proliferation and differentiation of human endometrioid endometrial carcinoma. Immunoexpression of cyclin D1 does not appear to be associated with cell-cycle progression in the benign or malignant endometrium.

Case-Control Studies↗

Clinicopathological study of the expression of syndecan-1 in invasive breast carcinomas. correlation with extracellular matrix components.

Syndecan-1, a cell surface proteoglycan found predominantly on epithelia of mature tissues, binds both extracellular matrix (ECM) components and basic fibroblast growth factor (bFGF) and is implicated in the restriction of growth and invasiveness of neoplastic cells, as it induces the adhesion capacity of neoplastic cells with the stroma. In this study we investigated breast carcinomas for the immunohistochemical expression of syndecan-1 protein and these results were assessed in relation to clinicopathological parameters, in order to clarify its prognostic value. The possible relationship with hormone receptors content, p53, cell proliferation markers, and extracellular matrix components was also estimated. Tissue sections from 102 breast carcinomas were used and immunostainings were performed on formalin-fixed, paraffin-embedded tissue sections by the labelled streptavidin avidin biotin (LSAB) method. High expression levels were observed, as 75/102 (73.5%) cases expressed immunoreactivity in more than 80% of neoplastic cells, while 67/102 (65.7%) exhibited high staining intensity. The survival analysis showed an increased mortality risk associated with high syndecan-1 staining intensity with borderline significance (p=0.041). In addition, there was a strong negative correlation between syndecan-1 protein expression and ECM, specifically collagen IV (p=0.026) and tenascin (p=0.0067). The results of the present study show the implication of this protein in the remodeling of breast cancer tissue, through the interaction with other extracellular matrix components, probably influences the tumour progression.

Avidin↗

Novel mutations of the APC gene in familial adenomatous polyposis in Greek patients.

Familial adenomatous polyposis (FAP), a premalignant clinical entity inherited as an autosomal dominant trait, is characterized by the development thousands of adenomatous polyps of the colorectum during the 2nd and 3rd decade of life. Approximately 80% of patients with FAP harbor truncating germline mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. We tested 24 members of six Greek families. All patients had the FAP phenotype, and one patient had an extracolonic tumor (medulloblastoma). Our method for testing was the polymerase chain reaction (PCR) amplification from genomic DNA extracted from whole blood, followed by automated DNA sequencing. Two novel truncating mutations (2601delGA and R923X) and three already-known mutations (R876X, Q1045X, and D1822V) were found. Other polymorphisms were also found. We identified the inactivating APC mutation in 12 of 13 of our FAP patients. Our results suggest that PCR sequencing is a reliable method for screening the APC gene for germline mutations.

Adenomatous Polyposis Coli↗

Clinicopathological study of the expression of hsp27, pS2, cathepsin D and metallothionein in primary invasive breast cancer.

Expression of the hormone-related proteins hsp27, pS2, and also of cathepsin D (CD) and metallothionein (MT) was studied by immunohistochemistry and analyzed against clinical data in breast cancer. Archived material of paraffin-embedded breast carcinoma tissues from a cohort of 134 patients with primary invasive breast cancer was used. Hsp27 and pS2 (>10% of tumor cells stained) were found to be expressed in 63.6% and 37.6% of cases, respectively, and were correlated negatively with grading (P=0.006 and 0.01) and positively with estrogen receptors (ER) (P=0.04 and 0.04). pS2 expression was correlated with lymph node status (P=0.02), tumor size (P=0.01), progesterone receptor (PR) content (P=0.02), hsp27 (P=0.015) and bcl-2 protein (P=0.001). An inverse relationship between pS2 expression and the expression of p53 protein (P=0.005) and proliferation-associated index MIB1 (P<0.0001) was noted. Stromal cathepsin D was positively correlated with tumor grade (P=0.01), PCNA (P=0.007), MIB1 (P=0.001) and p53 (P=0.01), and negatively with ER (P=0.04) and bcl-2 (P<0.0001). MT was correlated positively with stromal CD (P=0.007) and inversely with PgR (P=0.04). Univariate analysis showed CD expression to be a positive prognostic factor for survival (P=0.035), with borderline significance, while MT was more strongly positive (P=0.01). However, none of the proteins studied was found to be related to disease outcome in univariate analysis. Our data show that hsp27, pS2 and stromal CD expression may reflect tumor differentiation and the functional status of ER in breast cancer, but stromal CD and tumor MT expression were the only factors found that may be of limited prognostic value.

Adult↗

Increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas.

There is increasing evidence that bcl6 and CD10 expression may be related to apoptosis and cell cycle progression. Therefore, 79 cases of de novo diffuse large B-cell lymphomas were studied for the expression of bcl6 and CD10 proteins in relation to 1) the apoptotic index; 2) the proliferation-associated proteins Ki67, cyclin A, and cyclin B1; and 3) the expression of the bcl2, p53, Rb, p16, and p27 proteins. Expression of bcl6, CD10, and bcl2 proteins was found in 54/79 (68%), 28/79 (35%), and 47/74 (63%) cases, respectively. The bcl6/CD10 patterns were as follows: bcl6+/CD10+ (26 cases, 32%), bcl6+/CD10- (28 cases, 33%), bcl6-/CD10- (23 cases, 31%), and bcl6-/CD10+ (2 cases, 4%). Significant positive correlations were found between bcl6/Ki67 (r =.328, P =.003), bcl6/cyclin A (r =.265, P =.018), bcl6/apoptotic index (r =.327, P =.010), CD10/Ki67 (r =.296, P =.008), and CD10/apoptotic index (r =.397, P =.001). In addition, high expression of bcl6 showed significant correlation with negative (null/low) bcl2 expression (chi(2) test, P =.002). The above findings indicate that increased expression of the bcl6 and CD10 proteins is associated with increased apoptosis and proliferation in diffuse large B-cell lymphomas. The association between increased bcl6 expression and enhanced apoptosis might be due, at least in part, to the null/low bcl2 expression because previous in vitro data showed that bcl6 overexpression induces apoptosis accompanied by bcl2 and bcl-xl downregulation. Moreover, significant correlation was found between increased apoptotic index and the bcl6+/CD10+ pattern (t test: P =.014, Mann-Whitney test: P =.046). This finding and the positive correlation of the apoptotic index with bcl6 and CD10 expression may be related to previous results showing that the expression of these proteins has favorable effects on the clinical outcome of diffuse large B-cell lymphomas.

Apoptosis↗

Expression of cyclin D3 and cyclin E and identification of distinct clusters of proliferation and apoptosis in diffuse large B-cell lymphomas.

In the present study 79 cases of de novo Diffuse Large B-cell Lymphomas (DLBCL) were studied in order: a) to analyse the expression of cyclin D3, cyclin E and cyclin D1 in relation to other proliferative features (expression of Ki67, cyclin A and cyclin B1), the apoptosis status and the expression of p53, Rb, p16 and p27; and b) to determine whether distinct clusters of proliferation and apoptosis could be identified in DLBCL. Overexpression of cyclin D3 and cyclin E was found in 35/79 (43%) and 18/79 (22%) cases, respectively, whereas overexpression of cyclin D1 was not detected in any case. In most cases (39/46) overexpression of cyclin D3 and cyclin E was mutually exclusive possibly reflecting different underlying pathways inducing deregulated expression of these cyclins. In most cases (29/35) overexpression of cyclin D3 was mutually exclusive with Rb/p16 aberrant expression status supporting an oncogenic role for cyclin D3 and suggesting that the pathogenetic effect of cyclin D3 overexpression occurs through perturbation of the Rb1 pathway. Combined alterations of the P53 and the Rb/p16/cyclin D3 expression status were significantly associated with higher mean values of cyclin A (p=0.023) and cyclin B1 (p=0.033) indicating that concurrent impairment of the p53 and Rb1 pathways induces increased tumour cell proliferation in DLBCL. Cluster analysis of the apoptosis and the proliferation status permitted separation of DLBCL into distinct groups with low (44 cases) and high (18 cases) apoptotic activity and into distinct groups with low (32 cases), intermediate (36 cases) and high (11 cases) proliferative activity. The identification of distinct clusters with respect to the proliferation and the apoptosis status indicates that groups with distinct cellular kinetic properties can be defined in the histological group of DLBCL.

Apoptosis↗

Immunohistochemical expression of heat shock protein 27, in normal hyperplastic and neoplastic endometrium: correlation with estrogen and progesterone receptor status, p53, pRb and proliferation associated indices (PCNA, MIB1).

Heat shock protein 27 (HSP27) is a relatively small protein produced in response to pathophysiological stress. In the current prospective study the presence and localization of HSP27 was associated with other potential prognostic factors such as: estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA). One hundred and twenty-two samples of endometrial tissues (65 endometrial carcinomas, 28 adenomatous hyperplasias, 31 normal endometrium) were studied. Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology and lympho-vascular space invasion. HSPp27 expression was lower in the group of carcinomas when compared with the cases of adenomatous hyperplasias (p < 0.0001), normal proliferative (p < 0.0001) and secretory endometrium (p = 0.02). HSP27 expression was higher in carcinomas from premenopausal women in comparison with women in menopausal status and postmenopausal status. Multivariate tests showed no statistical significance of HSP27 expression according to tumor grade and stage. A positive relationship between the expression of HSP27 expression and estrogen receptors (p = 0.0018) as well as with progesterone receptor (p = 0.0012) was found with linear regression analysis of variance. Our data showed that the lower HSP27 expression in endometrial carcinomas in comparison with hyperplastic and normal endometrium may indicate a decreased endogenous protection mechanism against the various stressful stimuli. This expression could be under hormonal control and does not seem to be correlated with other conventional or possible prognostic parameters.

Adult↗

The current status of HPV DNA testing.

Infection with high-risk types of HPV underlies most cases of high-grade cervical intraepithelial neoplasia (CIN) and practically all cases of invasive cervical cancer. Currently, cervical HPV DNA is detected by means of PCR and sandwich capture molecular hybridization methods. Research has focused on the potential role of HPV testing in three conditions: screening for cervical neoplasia, triage of women with low-grade lesions and follow-up after conservative surgical treatment for CIN. Concerning the first condition, HPV testing does not seem to offer an obvious advantage over traditional cytology screening, mainly due to false positive results in younger women with transient HPV infection. A possible exemption to this is the case of middle-aged women and low-resource settings, where the excellent sensitivity of a HPV test is desirable. Although data are controversial regarding low grade lesions, results from randomized studies indicate that HPV testing could be useful in a triage of women with an initial cytological diagnosis of ASCUS, where detection of DNA of a high-risk type should lead to colposcopy. Although there is a lack of randomized controlled trials in this field, data from observational studies indicate that HPV DNA testing after conservative surgical treatment for CIN may be very sensitive and detect early residual and recurrent disease.

DNA, Viral↗

Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium. An immunohistochemical study including correlations with p53, steroid receptor status and proliferative indices (PCNA, MIB1).

PURPOSE OF INVESTIGATION: We have studied by immunohistochemistry the presence and localization of CD44, estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in order to determine their diagnostic and prognostic value as well as the possible correlations between them. METHODS: We examined 186 samples of endometrial tissue (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46 of normal endometrium). Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology, and lympho-vascular space invasion. RESULTS: Strong membranous immunostaining (> 10% of neoplastic cells) was observed in 45% of the carcinomas. A statistically significant correlation was found in the expression of protein in stromal cells, when compared with epithelial cells (p < 0.0001). Immunohistochemical expression of CD44 was significantly lower in cancer cases than in normal endometrium, mainly in the secretory phase (p < 0.0001). CD44 positive cases by immunohistochemistry failed to show any statistical correlation with tumor grade or with vessel invasion. The expression of the protein was lower in FIGO Stage II compared with Stage I (p = 0.03). A positive relation of CD44 expression with progesterone receptor status (p = 0.02) was detected. CD44 expression was also positively associated with the proliferation associated with the proliferative index MIB1 (p = 0.001). CONCLUSION: CD44 is closely related to the secretory phase of the normal menstrual cycle and its expression is decreased in hyperplasia (simple or complex with or without atypia) and in cancer cases. These observations suggest that decreased CD44 expression might be functionally involved in the multiple mechanisms of the development and progression of endometrial lesions.

Biomarkers, Tumor↗

Factors affecting outcome after incomplete excision of cervical intraepithelial neoplasia.

PURPOSE: Conservative treatment for cervical intraepithelial neoplasia (CIN) by ablative or excisional techniques is widely used. However, women with incomplete excision have a variable risk of CIN recurrence. The aim of this study was to identify possible risk factors for recurrence of CIN after large loop excision of the transformation zone (LLETZ) with involved margins of excision. METHODS: All cases of women treated with LLETZ for CIN between 1989-2000, in whom histological evaluation of the excised specimen revealed extension of CIN to the excision margins, were retrospectively studied. A woman was considered to have recurrence when she had histologically confirmed CIN following a second LLETZ or hysterectomy during the follow-up period. The characteristics that were examined as possible risk factors were age, parity, smoking habit, grade of initial lesion and extension to the endo- or ectocervical margin. RESULTS: Treatment failure was diagnosed in 18 out of 65 (27.7%) women with involved margins. The only characteristic that reached statistical significance was age. The mean age of women with recurrence was 35.8 years, whereas the mean age of women without recurrence was 32.8 years (p = 0.044). Also, a trend was evident in women with high-grade initial lesions (CIN II-III) (p = 0.168) and involvement of the endocervical margins (p = 0.149). No differences were observed between the two groups regarding parity and smoking habit. CONCLUSIONS: Increased age is a risk factor for recurrence in women with incomplete excision of CIN after LLETZ. Larger studies are required for definite conclusions.

Adult↗