Biomedical subjects

H W Carter

Publications and source records attributed to H W Carter.

At least 19 recordsLinked to original sources

PubMed2001

Integrin-linked kinase expression increases with prostate tumor grade.

PURPOSE: Integrin-linked kinase (ILK) overexpression can suppress anoikis, promote anchorage-independent cell cycle progression, and induce tumorigenesis and invasion. Inhibition of ILK in prostatic adenocarcinoma (CaP) cells elicits cell cycle arrest and induces apoptosis. Furthermore, ILK expression increases with androgen-independent progression of human CaP cell lines, suggesting that increased ILK expression may be associated with CaP progression. EXPERIMENTAL DESIGN: To assess whether ILK expression may be related to CaP development and/or progression, we have evaluated ILK expression by immunohistochemistry in 100 human prostate tissues. RESULTS: We show that ILK expression increases significantly with CaP progression. ILK immunostaining is specifically increased in high-grade, primary human CaP relative to adjacent benign prostatic hyperplasia (P < 0.001), benign prostatic hyperplasia from patients without cancer (P < 0.002), and low-grade CaP (P = 0.003). ILK overexpression is specifically associated with the increased proliferative index (P = 0.001) that typifies CaP progression. Strikingly, intense uniform ILK immunostaining was inversely related to 5-year patient survival (P = 0.004). CONCLUSIONS: ILK expression increases dramatically with CaP progression. ILK expression is also specifically related to the disproportionately increased proliferative index that contributes to the net gain of CaP cells during progression. Finally, enhanced ILK expression is inversely related to 5-year patient survival. These data therefore implicate increased ILK expression in prostate tumor progression.

Adenocarcinoma↗

PubMed2001

Expression of group IIa secretory phospholipase A2 increases with prostate tumor grade.

PURPOSE: Arachidonate release contributes to prostate tumor progression as arachidonate is metabolized into prostaglandins and leukotrienes, potent mediators of immune suppression, cellular proliferation, tumor motility, and invasion. The group IIa sPLA2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids. We therefore sought to determine whether sPLA2-IIa expression might be related to the development or progression of prostatic adenocarcinoma (CaP). EXPERIMENTAL DESIGN: sPLA2-IIa expression was examined by Western blot analyses of CaP cells and xenografts and by immunohistochemistry of benign prostatic hyperplasias and primary human CaPs (n = 101) using a sPLA2-IIa-specific polyclonal antibody. RESULTS: sPLA2-IIa expression was increased dramatically in the androgen-independent CWR-22R and LNAI CaP cells versus the androgen-dependent CWR-22 and LNCaP cells. Immunohistochemical analyses revealed that sPLA2-IIa expression was also significantly increased with CaP development and advancing disease (trend analysis; Pearson correlation coefficient, P = 0.016). High-grade CaPs showed intense, uniform staining for sPLA2-IIa that was significantly different from that in adjacent benign prostatic hyperplasias (Fisher's exact test, P = 0.021) or low-grade CaP (P = 0.013), both of which showed only focal or weak sPLA2-IIa staining. Further, uniform sPLA2-IIa expression was directly related to the increased proliferative index that typifies advancing disease (P = 0.001). Most significantly, enhanced sPLA2-IIa expression was inversely related to 5-year patient survival (P = 0.015). CONCLUSIONS: These data show that sPLA2-IIa expression increases with progression to androgen-independence and is highest in the most poorly-differentiated, highest-grade primary human CaP samples.

Androgens↗

PubMed1997

Validation of the galactose oxidase-Schiff's reagent sequence for early detection and prognosis in human colorectal adenocarcinoma.

Based on the multistage and multifocal nature of colorectal carcinogenesis, it is likely that reduction of cancer mortality through early detection and identification of new prognostic markers is an attainable goal. Well-documented changes occur in mucin glycoconjugates during neoplastic progression in the colon, and the nonneoplastic colonic mucosa in colon cancer patients is morphologically and histochemically abnormal. In this retrospective study, 152 archival colorectal tissues from 49 patients were studied for changes in mucin secretions as detected by the galactose oxidase-Schiff's (GOS) sequence. Intensity of the stain was evaluated in histological sections by semiquantitative analysis, and the area percentage of epithelium stained was quantified by image cytometry. The correlation between gender or tumor size, location and reactivity with peanut agglutinin and quantitative expression of GOS-reactive mucins was determined as well as intratumor and inter individual variability. Reactivity with GOS: (a) decreased during neoplastic progression and malignant conversion in the neoplasm; (b) increased in the normal colonic mucosa of patients with progressively more advanced disease; and (c) was of prognostic significance for patient survival or recurrence both in the normal colon of cancer patients and in invasive neoplasms. These data are consistent with the conclusion that GOS reactivity in the normal colonic mucosa is a dosimeter of exposure to environmental/lifestyle colorectal carcinogens rather than a marker for an oncodevelopmental cancer-associated antigen.

Adenocarcinoma↗

PubMed1996

Hepatocyte expression of tumor associated aldehyde dehydrogenase (ALDH-3) and p21 Ras following diethylnitrosamine (DEN) initiation and chronic exposure to di(2-ethylhexyl)phthalate (DHEP).

Phthalate esters such as di(2-ethylhexyl)phthalate (DEHP) either promote or inhibit rat liver tumorigenesis depending on the carcinogenesis protocol. In this study, we examined the expression of two histochemical markers, the tumor associated isozyme of aldehyde dehydrogenase (ALDH-3) and the oncoprotein p21 Ras, in the livers of male F344 rats. The rats were initiated with DEN and further treated with either DEHP (a known inhibitor of hepatocarcinogenesis), phenobarbital (PB, a known promoter of hepatocarcinogenesis), or a combination of DEHP and PB. The studies were designed to examine the expression of these markers in both normal appearing liver and hepatic hyperplastic and neoplastic lesions and to correlate the early expression of the markers at 26 weeks in the normal appearing liver to later tumor incidence at 52 weeks. The expression of each marker was detected by immunohistochemical methods on formalin-fixed paraffin embedded sections of normal appearing liver or liver lesions. We found that ALDH-3 and p21 expression were significantly enhanced in rats receiving PB after DEN initiation at 26 weeks and that the incidence of hepatocellular carcinomas was likewise increased compared to control or DEN only treated animals. DEN initiation followed by a combination of PB and either 0.1 or 0.5% DEHP significantly reduced ALDH-3 but not p21 Ras expression at 26 weeks compared to DEN plus PB only. These treatment regimens also reduced the incidence of hepatocellular carcinomas at 52 weeks. DEN followed by any of the three doses of DEHP without PB resulted in ALDH-3 expression similar to DEN alone. However, p21 Ras expression was significantly increased after these treatments. For all treatment groups, both the early (26 weeks) expression of p21 Ras and ALDH-3 correlated with hepatocellular carcinoma incidence at 52 weeks. However, the correlation between hepatocellular carcinoma and ALDH-3 expression was better than p21 Ras or the other markers we have studied. We concluded that ALDH-3 expression is significantly downregulated after DEHP treatment, and that expression of the isozyme correlated with later hepatocarcinoma incidence and may indicate a significant relationship between ALDH-3 expression and hepatocarcinogenesis during DEHP treatment.

Aldehyde Dehydrogenase↗

PubMed1995

In vivo administration of dichloroacetic acid suppresses spontaneous apoptosis in murine hepatocytes.

Spontaneous apoptosis in hepatocytes of male B6C3F1 mice that received dichloroacetic acid (DCA) in their drinking water for 5-30 days (28-58 days of life) was examined as part of ongoing studies to determine the molecular basis of the hepatocarcinogenicity of this nongenotoxic water chlorination by-product. DCA at 0.5 and 5.0 g/liter, significantly reduced apoptosis relative to untreated controls in a dose-dependent fashion. Regression analysis indicated that apoptosis declined over the 30-day period in the livers of control, age-paired animals receiving no drug. Animals receiving low-dose DCA exhibited a similar, although quantitatively depressed, trend line, whereas animals receiving high-dose DCA showed maximal depression of apoptosis at 5 days, which was sustained throughout the course of the 30-day period. These studies suggest that DCA has the ability to down-regulate apoptosis in murine liver. When taken together with previous data demonstrating DCA-dependent decrease in labeling index in these same livers, these data further support the hypothesis that the carcinogenic mechanism of DCA may involve suppression of the ability of the liver to remove initiated cells by apoptosis rather than by induction of selective proliferation of initiated cells.

Animals↗

PubMed1995

Immunohistochemical analysis of dichloroacetic acid (DCA)-induced hepatocarcinogenesis in male Fischer (F344) rats.

We examined the incidence of proliferative lesions, hyperplastic nodules and altered hepatic foci, in male F344 rat liver, to determine their preneoplastic potential during dichloroacetic acid (DCA)-induced hepatocarcinogenesis. Immunohistochemical and image analysis methods were used to detect the expression of 6 histochemical markers of neoplastic cells; p21 ras, p39 c-jun, p55 c-fos, aldehyde dehydrogenase (ALDH), glutathione s-transferase (GST-p), and alpha fetoprotein (AFP) during DCA-induced hepatocarcinogenesis. Our results were consistent with our previous data and suggested that the hyperplastic nodules, rather than altered hepatic foci, is a putative preneoplastic lesion during DCA-induced hepatocarcinogenesis in the male F344 rat.

Aldehyde Dehydrogenase↗

PubMed1995

Biochemical, pathologic and morphometric alterations induced in male B6C3F1 mouse liver by short-term exposure to dichloroacetic acid.

Dichloroacetic acid (DCA) is a complete hepatocarcinogen and tumor promoter in the male B6C3F1 mouse. Published reports indicate that the compound is non-genotoxic. This study examines possible non-genotoxic (epigenetic) mechanisms by which DCA elicits its carcinogenic response. Correlative biochemical, pathologic and morphometric techniques are used to characterize and quantify the acute, short-term response of hepatocytes in the male B6C3F1 mouse to drinking water containing DCA. Cellularity, [3H]thymidine incorporation, DNA concentration, nuclear size, and binuclearity are evaluated in terms of level of exposure (0, 0.5 and 5 g/l) and length of exposure to DCA. The dose-related alterations in hepatocytes of animals exposed to DCA for 30 days or less indicate that short-term exposure to DCA results in inhibition of mitoses, alterations in cellular metabolism and a shift in ploidy class. Thus, DCA carcinogenesis may involve cellular adaptations, development of drug resistance and selection of phenotypically altered cells with a growth advantage.

Analysis of Variance↗

PubMed1993

Immunohistochemical detection of RAS, JUN, FOS, and p53 oncoprotein expression in human colorectal adenomas and carcinomas.

BACKGROUND: Recent evidence suggests that progressive stages of colorectal tumorigenesis can be defined by a sequence of genetic events characterized by deletion and expression of certain genes and appearance of several oncoproteins. Although the significance of these events is not entirely clear, oncoprotein expression may be directly involved in the tumorigenic mechanism. EXPERIMENTAL DESIGN: We examined the expression of two nuclear oncoproteins, JUN and FOS (Abbreviations used in this paper are lower case letters for oncogenes and upper case letters for oncoproteins), that have not been previously associated with development of colorectal cancer. This study involved detecting p39 c-JUN and p55 c-FOS, as well as two oncoproteins previously known to be expressed during colorectal tumorigenesis, p21 RAS and the tumor suppressor protein, p53. Expression was detected with immunohistochemical methods on formalin-fixed, paraffin-embedded sections of normal human colons, tubular adenomas, tubulovillous adenomas, and adenocarcinomas. Either single oncoprotein expression or coexpression of four selected pairs; RAS/JUN, RAS/FOS, RAS/p53, or JUN/FOS were evaluated. RESULTS: We found that the expression of all four single oncoproteins and oncoprotein pairs were detected in very few normal colon specimens or tubular adenomas. However, all four oncoproteins and the four oncoprotein pairs were expressed significantly more often in adenocarcinomas. Oncogene expression in tubulovillous adenomas varied with lesion size. The number of lesions expressing any of the four oncoproteins or pairs was not significantly different than normal colon in small (< 1 cm diameter) tubulovillous adenomas. Significantly more large lesions (> 1 cm. diameter) expressed the single oncoproteins RAS, JUN, and FOS than normal colon. Of the four oncoprotein pairs, only RAS/JUN was significantly coexpressed in large tubulovillous adenomas. CONCLUSIONS: We conclude that independent expression of RAS, JUN, and FOS occurred significantly more often in large tubulovillous adenomas and adenocarcinomas while p53 expression occurred primarily in adenocarcinomas. Also, although all four oncoprotein pairs were expressed significantly more often in adenocarcinomas, only RAS/JUN was significantly coexpressed in the large tubulovillous adenomas. These results are comparable with the observed sequential activation of Ki-ras and p53 described by others and suggests that the expression of the nuclear oncogenes, JUN and/or FOS, are also important events in colorectal tumorigenesis.

Adenocarcinoma↗

PubMed1992

Quantitative image cytometry of hepatocytes expressing gamma-glutamyl transpeptidase and glutathione S-transferase in diethylnitrosamine-initiated rats treated with phenobarbital and/or phthalate esters.

Image cytometry was used to quantify the volume of liver expressing two histochemical markers associated with neoplasia, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P). Rats were treated with diethylnitrosamine (DENA) followed by phenobarbital (PB), di(2-ethylhexyl)phthalate (DEHP), or di-n-octyl-phthalate (DOP) for 26 weeks. In one series, PB-treated rats were given 2.0%, 0.5%, or 0.1% DEHP in the feed. GGT expression was detected diffusely throughout the liver parenchyma in several treatment groups so that any enhanced expression in altered foci (AF) and nodules (N) was not apparent. GST-P was detected only in AF and N. GST-P may represent a second genetic alteration, as GST-P+ AF and N also expressed GGT but not the reverse. The peroxisome proliferator DEHP inhibited expression of GGT or GST-P in livers of either DENA-treated or DENA+PB-treated rats. With GST-P the reduction was correlated to a reduced number of AF and N. In contrast, DEHP's stereoisomer, DOP, was as effective as PB in promoting expression of both markers. We conclude that image cytometry of hepatocytes expressing GST-P can be used in the bioassay of the carcinogenic potential of chemicals that affect liver proliferation.

Animals↗

PubMed1990

Studies in red blood cell preservation. 3. A phosphate-ammonium-adenine additive solution.

The maintenance of adenosine triphosphate (ATP) in red blood cells (RBC) during storage is largely dependent on the integrity of glycolytic metabolism in the Embden-Meyerhof pathway. Meryman et al. [Transfusion 1986; 26:500-505] hypothesized that a solution that increased the surface tension of the corpuscles through hypotonic swelling might retard the development of echinocytosis and membrane loss by the shedding of exocytic vesicles. Unexpectedly, maintenance of good ATP levels and satisfactory RBC survivals were found for a long as 18 weeks. The purpose of our study was to test their observations and to explore the possible mechanisms. Equal parts of units of packed RBC were stored in the experimental preservative and, for comparison, in ADSOL. The most notable findings were ATP values at 4 weeks averaging 5.2 mumol/g Hb (130% of initial) and at 12 weeks 2.9 mumol/g Hb (73% of initial), whereas these values declined as expected in ADSOL. Mean RBC diameters and surface areas by morphometric analysis were not significantly different in the two preservatives indicating the absence of any hypotonic swelling. The morphology scores of the RBC were significantly better throughout (p less than 0.05) than in ADSOL. The shedding of exocytic hemoglobin-containing vesicles was essentially the same in both preservatives. Our data confirm the observation that ATP levels are well maintained for at least 12 weeks, but do not show any evidence that hypotonic swelling was a part of the mechanism.

Adenine↗

PubMed1988

Adrenal regulation of mammary tumorigenesis in female Sprague-Dawley rats: incidence, latency, and yield of mammary tumors.

Huggins and Morii (J. Exp. Med., 114: 741, 1961) reported that massive adrenal necrosis occurs in 79 and 100% of female Sprague-Dawley rats receiving 20 and 30 mg, respectively, of the mammary carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Here, adrenal necrosis and regeneration were studied in 158 rats for up to 21 days post-DMBA by radioautography of the adrenals of animals given 50 microCi [3H]thymidine 30 min before sacrifice. Adrenal cell proliferation was markedly inhibited 21 days post-DMBA. Regenerated adrenals were more susceptible to this adrenocorticolytic effect. To investigate if alterations in adrenal function modify tumorigenesis, animals underwent adrenalectomies (ADX), hypophysectomies, ovariectomies, and pituitary transplants alone or in combination 6 days after receiving DMBA (20 mg/100 g intragastrically) at 50 days of age. To prevent adrenal necrosis, 24 animals were pretreated with metyrapone. Methylprednisolone acetate, 1 mg i.m., was given to 40 animals every 5 days beginning 6 days post-DMBA. There were 50 non-DMBA-treated intact and surgical controls. DMBA was necessary but not sufficient to induce mammary tumors. No tumors developed in controls or in 46 animals hypophysectomized 6 days after DMBA. Metyrapone reduced tumor incidence and yield. ADX after DMBA treatment increased the tumorigenic response and eliminated resistance to tumorigenesis in older rats. Only three tumors developed in DMBA-treated rats receiving methylprednisolone acetate. Mammary tumorigenesis was increased by pituitary transplant 6 days after DMBA to intact and ADX animals. Ovariectomy 6 days after DMBA was as effective as methylprednisolone acetate in preventing tumorigenesis; ADX did not overcome either inhibition. We conclude that adrenal hormones inhibit proliferation of initiated mammary cells.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1988

Adrenal regulation of mammary tumorigenesis in female Sprague-Dawley rats: histopathology of mammary tumors.

Mammary tumors induced in female Sprague-Dawley rats by feeding 7,12-dimethylbenz(a)anthracene (DMBA; 20 mg/100 g body weight) were classified according to histological criteria of tissue differentiation, cellular atypia, and evidence of invasion. The 549 tumors could be placed in three categories, nodular hyperplasia, nodular hyperplasia with atypia, and carcinoma, and combinations of all three. Although tumors classified histologically as carcinomas did not metastasize, upon transplantation to the kidney capsule, a tumor classified as a carcinoma grew for eight generations and metastasized. Tumor heterogeneity was a common finding in DMBA-initiated tumors. Carcinomas were an early lesion. As the length of time between DMBA treatment and sacrifice increased, more tumors with areas of carcinoma were found. Therefore, DMBA-initiated tumors progressed to carcinomas either soon after initiation or later by development within nodular hyperplasias. In 4 separate groups of animals (74 adrenalectomized rats and 90 intact rats), postinitiation adrenalectomy increased the numbers of carcinomas compared to intact animals. This effect was consistently seen in the cervical and thoracic mammary glands. We propose that the mechanism for enhancement of progression to greater malignancy by adrenalectomy may be inhibition of differentiation of initiated cells in the absence of glucocorticoids.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1988

Quantitative and qualitative immunohistochemical detection of myc and src oncogene proteins in normal, nodule, and neoplastic rat liver.

This study examined the possibility of using an immunohistochemical technique to detect the expression of myc and src oncogene proteins (ops) in livers of male Sprague-Dawley rats after treatment with the carcinogen diethylnitrosamine (with or without phenobarbital promotion) or untreated. We found that the majority of nodules and tumors from these livers stained for myc and src ops, indicating that myc and src expression did occur in these structures. These results were expected, since myc and src expression has been previously observed by others using different techniques. However, in our study, myc and src op staining was also noted in normal liver areas from rats in any of the four treatment groups (DENA, DENA + PB, PB alone, or untreated). The staining pattern of normal liver was different for each oncogene probe but was consistent within the four groups. In most cases, oncogene expression of normal liver occurred at sites of abnormal (but non-neoplastic) hepatocytes. The method reported here used both a qualitative technique of op expression analysis and a quantitative method using a Zeiss computer-driven image analysis system.

Animals↗

PubMed1983

Studies of eosinophil medusa cells by electron imaging modes.

Medusa cells, amoeboid variants of the eosinophil with pseudopod-like processes, were examined by light microscopy (LM), transmission electron microscopy (TEM), the secondary electron imaging (SEI) and the backscattered electron imaging (BEI) modes of the scanning electron microscope. TEM was performed on rare medusa cells found in leukocyte concentrate preparations where the ion contents of the collection and fixation media were balanced so that divalent cations such as calcium and magnesium were not sequestered. LM, SEI and BEI studies were performed principally on cytochemically-stained films of leukocyte concentrate preparations on microscope slides or coverslips. These films of patients with eosinophilia contained many medusa cells and much higher ratios of medusa cells to eosinophils than critical point-dried specimens, if they were prepared as for routine hematologic examination, and precautions were taken to insure that calcium and magnesium ions in collection and fixation media were not sequestered. After brief glutaraldehyde fixation, the smears were stained with either osmium tetramethylethylenediamine (Os-TMEDA) for acid mucopolysaccharides, or 3,3'-diaminobenzidine (DAB)/hydrogen peroxide medium for peroxidases. The Os-TMEDA was sufficiently conductive for SEM. Chelation of the oxidatively-polymerized DAB dye with copper nitrate rendered it conductive. These conductive and electron-opaque stains permitted the correlation of SEI with BEI on individual cells, their unambiguous identification as eosinophils or medusa cells and their differentiation from other leukocytes by virtue of content and/or size of their granules and their degree of nuclear segmentation.

Cell Separation↗

PubMed1983

Morphologic alterations induced by short-term cigarette smoking.

Pulmonary fibrosis and emphysema were produced in beagle dogs by their direct inhalation of cigarette smoke over a relatively short period of time (2-7 cigarettes daily for 2-4 months). One dog was sacrificed after having smoked 172 cigarettes, one after 282 cigarettes, and the others after 480 and 534 cigarettes, respectively. Examination of the lungs by scanning and transmission electron microscopy showed a range of response from the presence of numerous smoker's macrophages to extensive alterations, including destruction and enlargement of alveolar ducts and varying degrees of enlargement of alveolar spaces. Interalveolar pores were enlarged, and marked fenestration leading to destruction of the alveolar walls became apparent. These features were accompanied by interstitial fibrosis of the interalveolar septa. Light- and electron-microscopic examination showed no evidence of bronchitis and/or bronchiolitis or of physical obstruction to the terminal airways in the early development of fibrosis and emphysema.

Animals↗

PubMed1982

A comparison of World Health Organization (WHO) classification of lung tumors by light and electron microscopy.

Forty-nine cases of lung tumor were initially classified according to the World Health Organization (WHO) system by light microscopy. Additional study by electron microscopy using only a minimum of ultrastructural features as criteria for each type made more precise classification of some of the poorly differentiated or undifferentiated tumors possible. Most significant was the finding of evidence of a second tumor type in nine of the 35 tumors previously classified as moderately to well differentiated thus reclassifying them as mixed tumors. Sixteen of the 49 tumors were reclassified and a more precise classification was made in five others. Only two cases of undifferentiated small cell tumors were available and no unequivocal neurosecretory granules could be found in either. Correlation of the more precise typing of lung tumors by electron microscopy with the clinical data and modes of therapy will provide necessary information for determining the usefulness of the WHO classification.

Adenocarcinoma↗

PubMed1981

Comparison of selective staining of fungi in paraffin sections by light microscopy, SEM and BEI.

Paraffin-embedded sections from human tissues with fungi or organisms classified with fungi were studied by light microscopy (LM), scanning electron microscopy (SEM), and the backscatter electron imaging (BEI) mode of the SEM. The fungal organisms selected for study were those familiar to the pathologist on the basis of their appearance in paraffin-embedded material stained with the Gomori-Grocott Chromic Acid Methenamine Silver Stain (GMS). The organisms were Actinomyces, Rhizopus, Cryptococcus, Histoplasma capsulatum, and Coccidia imitis. Sections were stained with the GMS Stain and/or the Becker modification of the GMS Stain (BGMS) and examined in the secondary electron imaging mode (SEI) and BEI mode with an annular backscatter electron detector. This silver staining technique accentuated the wall of fungal organisms, in the backscatter mode. Depending on the fungal organism and type of silver stain employed, the GMS seemed the preferable stain. The advantages of SEM over LM were greater depth of focus and potential range of magnifications. BEI may also be used in conjunction with LM stain for microorganisms to establish their presence.

Actinomyces↗

PubMed1980

Spindle cell sarcoma of scrotum.

Sarcomas of paratesticular origin are rare tumors. They usually manifest themselves as a scrotal mass that should be differentiated from testicular tumors. There are problems regarding their pathologic diagnosis and treatment. We report a case of spindle cell sarcoma of the gubernaculum testis in a young patient. Electron microscopy was used in the histogenetic typing of this tumor.

Adolescent↗