OESTRADIOL-17β UPTAKE IN VITRO INTO THE NUCLEI OF ENDOMETRIUM FROM DIFFERENT REGIONS OF THE HUMAN UTERUS

C. B. Lunan; B. Greenz

doi:10.1530/acta.0.0780353

OESTRADIOL-17β UPTAKE IN VITRO INTO THE NUCLEI OF ENDOMETRIUM FROM DIFFERENT REGIONS OF THE HUMAN UTERUS

Acta Endocrinologica ◽

10.1530/acta.0.0780353 ◽

1975 ◽

Vol 78 (2) ◽

pp. 353-363 ◽

Cited By ~ 6

Author(s):

C. B. Lunan ◽

B. Greenz

Keyword(s):

Regional Differences ◽

The State ◽

Nuclear Accumulation ◽

Lower Body ◽

Human Uterus ◽

Secretory Phase ◽

Body Regions

ABSTRACT Specimens of endometrium from the vault, body and lower body regions of the same human uteri were incubated separately for 30 min in vitro in the presence of 1–6 × 10−9m 3H-oestradiol. Uptake into the nuclei was variable but in general the vault region endometrium was least active in nuclear accumulation of the hormone, especially in secretory phase endometrium. This suggests that intra-uterine variations found in oestradiol uptake in vivo are due to regional differences in the state of the tissue itself.

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Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

Scientific Reports ◽

10.1038/s41598-021-92871-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ryosuke Nakamura ◽

Nao Hiwatashi ◽

Renjie Bing ◽

Carina P. Doyle ◽

Ryan C. Branski

Keyword(s):

Vocal Fold ◽

Vocal Folds ◽

Nuclear Accumulation ◽

Smad Pathway ◽

Surgical Interventions ◽

Smad Signaling ◽

Iatrogenic Damage ◽

Tgf Β1

AbstractVocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

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Tocotrienols and Cancer: From the State of the Art to Promising Novel Patents

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892814666190116111827 ◽

2019 ◽

Vol 14 (1) ◽

pp. 5-18 ◽

Cited By ~ 8

Author(s):

Fabrizio Fontana ◽

Michela Raimondi ◽

Monica Marzagalli ◽

Roberta M. Moretti ◽

Marina Montagnani Marelli ◽

...

Keyword(s):

Cancer Prevention ◽

State Of The Art ◽

Synergistic Effects ◽

The State ◽

Therapeutic Interventions ◽

Multiple Tumor ◽

Anti Cancer ◽

Important Health

Background: Tocotrienols (TTs) are vitamin E derivatives naturally occurring in several plants and vegetable oils. Like Tocopherols (TPs), they comprise four isoforms, α, β, γ and δ, but unlike TPs, they present an unsaturated isoprenoid chain. Recent studies indicate that TTs provide important health benefits, including neuroprotective, anti-inflammatory, anti-oxidant, cholesterol lowering and immunomodulatory effects. Moreover, they have been found to possess unique anti-cancer properties.Objective:The purpose of this review is to present an overview of the state of the art of TTs role in cancer prevention and treatment, as well as to describe recent patents proposing new methods for TTs isolation, chemical modification and use in cancer prevention and/or therapy.Methods:Recent literature and patents focusing on TTs anti-cancer applications have been identified and reviewed, with special regard to their scientific impact and novelty.Results:TTs have demonstrated significant anti-cancer activity in multiple tumor types, both in vitro and in vivo. Furthermore, they have shown synergistic effects when given in combination with standard anti-cancer agents or other anti-tumor natural compounds. Finally, new purification processes and transgenic sources have been designed in order to improve TTs production, and novel TTs formulations and synthetic derivatives have been developed to enhance their solubility and bioavailability.Conclusion:The promising anti-cancer effects shown by TTs in several preclinical studies may open new opportunities for therapeutic interventions in different tumors. Thus, clinical trials aimed at confirming TTs chemopreventive and tumor-suppressing activity, particularly in combination with standard therapies, are urgently needed.

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THE ACTION OF THE SYNTHETIC POLYPEPTIDE VALYL-OXYTOCIN ON THE HUMAN UTERUS IN VITRO AND IN VIVO

Acta Endocrinologica ◽

10.1530/acta.0.xxxii0391 ◽

1959 ◽

Vol XXXII (III) ◽

pp. 391-398 ◽

Cited By ~ 10

Author(s):

B. Berde ◽

K. Saameli

Keyword(s):

Human Uterus ◽

Synthetic Polypeptide

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Analysis of elongating morphogenesis of quail anterior submaxillary gland: absence of localized cell proliferation

Development ◽

10.1242/dev.62.1.229 ◽

1981 ◽

Vol 62 (1) ◽

pp. 229-239

Author(s):

Hiroyuki Nogawa

Keyword(s):

Cell Proliferation ◽

Basement Membrane ◽

Regional Differences ◽

Submaxillary Gland ◽

Mesenchymal Cells ◽

Submaxillary Glands ◽

Parallel Direction ◽

Recombination Experiments

Quail anterior submaxillary glands elongated extensively without branching (more than sevenfold) from 8 to 10 incubation days. Investigation of mitotic activity of the rudiments in vivo showed no localized cell proliferation throughout the rudiments, and recombination experiments in vitro to examine regional differences in mitogenic activity of the surrounding mesenchyme also showed that no mesenchymal region specifically stimulates the epithelial cell proliferation. Histological observation of the rudiments showed that epithelial cells did not lengthen in a parallel direction to the long axis of the rudiment, and that mesenchymal cells encircled the epithelial cord perpendicularly to its axis. The basement membrane was obscure in the distal end of the rudiments, while it was easily detected in the other part of the rudiments. These results suggest that the elongating morphogenesis of the anterior submaxillary rudiments is not achieved by localized cell proliferation but by almost uniformly distributed cell proliferation, and mesenchymal cells surrounding the rudiment or the basement membrane may be involved in the controlling mechanisms of the elongating morphogenesis.

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Effects of epinephrine on regional free fatty acid and energy metabolism in men and women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.2.e259 ◽

1996 ◽

Vol 270 (2) ◽

pp. E259-E264 ◽

Cited By ~ 14

Author(s):

M. D. Jensen ◽

P. E. Cryer ◽

C. M. Johnson ◽

M. J. Murray

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Fat Distribution ◽

Normal Weight ◽

Upper Body ◽

Lower Body ◽

Men And Women

Upper-body and lower-body adipocytes respond differently to physiological catecholamines in vitro. It is not known whether this is true in vivo or whether gender differences exist in the regional adipose tissue responses to epinephrine. These studies were therefore conducted to examine free fatty acid (FFA) release ([3H]palmitate) from lower-body (leg), splanchnic, and upper-body adipose tissue in normal-weight adult men (n = 8) and women (n = 7). In response to intravenous epinephrine (10 ng.kg-1.min-1), palmitate release increased (P < 0.01) in both men (168 +/- 10 to 221 +/- 15 mumol/min) and women (177 +/- 12 to 234 +/- 18 mumol/min). Basal leg palmitate release was similar in women and men (16.8 +/- 2.9 and 12.4 +/- 1.3 mumol/min, P = not significant) but doubled (P < 0.01) in response to epinephrine in men and was virtually unchanged in women. Splanchnic palmitate release increased (P < 0.05) in men (n = 6) but not in women (n = 6), whereas nonsplanchnic upper-body palmitate release increased more in women than in men. Upper-body (splanchnic and nonsplanchnic) palmitate release increased (P < 0.05) in both men and women in response to epinephrine. In summary, lower-body adipose tissue FFA release increased in response to epinephrine in men but not women, whereas upper-body palmitate release increased in both groups. These findings are consistent with some in vitro findings and suggest that catecholamine action may play a role in determining gender-based differences in body fat distribution.

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THE SPECIFICITY OF ALLERGIC REACTIONS

Journal of Experimental Medicine ◽

10.1084/jem.117.3.401 ◽

1963 ◽

Vol 117 (3) ◽

pp. 401-423 ◽

Cited By ~ 22

Author(s):

John E. Coe ◽

S. B. Salvin

Keyword(s):

Immune Response ◽

Guinea Pig ◽

The State ◽

Delayed Hypersensitivity ◽

Protein Carrier ◽

Specific Contact ◽

Tolerant Animal ◽

Gastric Feeding

"Gastric feeding" of adult guinea pigs with dinitrochlorobenzene (DCB) resulted in a specific unresponsiveness to sensitization with the specific contact hapten. The more DCB gastric-fed to a guinea pig, the more complete the unresponsiveness to the hapten. When mycobacteria were incorporated into the sensitizing emulsion, the state of unresponsiveness to the dinitrophenyl (DNP) group was less apparent. When animals gastric-fed with DCB were later sensitized with an in vitro conjugate of the hapten combined with a heterologous protein such as dinitrophenyl-hen egg albumin (DNP·HEA), an immune response similar to that in the controls occurred both to the hapten and to the protein carrier. However, when the tolerant animals were sensitized with a conjugate containing a homologous protein carrier such as dinitrophenyl guinea pig serum (DNP·GPS), they showed diminished immune responses in comparison with those in the non-tolerant controls. The presence of circulating anti-DNP antibodies from sensitization with DNP-HEA did not affect the unresponsiveness to the specific contact hapten, regardless of whether these antibodies are present before or after induction of tolerance. Sensitization with picryl chloride (PiCl) (a cross-reacting hapten), either before or after gastric feeding of DCB, did not affect the state of unresponsiveness to DNP. Similarly when the DNP-tolerant animal was sensitized with PiCl, the subsequent immune response was similar to that in the controls; cross-reactions with the DNP group both in the contact and circulating antibody phase occurred at a rate similar to that in the controls. The foregoing relationships can be explained by presuming that, upon the gastric feeding of DCB, an in vivo conjugate is formed with a somatic protein, which determines the basic specificity of the tolerance. Acquired tolerance seems to manifest an immunologic specificity similar to that of delayed hypersensitivity, a relationship not unexpected if delayed hypersensitivity is an early phase of the immune response.

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Modulating PKCα Activity to Target Wnt/β-Catenin Signaling in Colon Cancer

Cancers ◽

10.3390/cancers11050693 ◽

2019 ◽

Vol 11 (5) ◽

pp. 693 ◽

Cited By ~ 5

Author(s):

Sébastien Dupasquier ◽

Philippe Blache ◽

Laurence Picque Lasorsa ◽

Han Zhao ◽

Jean-Daniel Abraham ◽

...

Keyword(s):

Transcriptional Activation ◽

Transcriptional Activity ◽

Target Genes ◽

Tumor Development ◽

Orphan Receptor ◽

Nuclear Accumulation ◽

Kinase C ◽

Extracellular Signal

Inactivating mutations of the tumor suppressor Adenomatosis Polyposis Coli (APC), which are found in familial adenomatosis polyposis and in 80% of sporadic colorectal cancers (CRC), result in constitutive activation of the Wnt/β-catenin pathway and tumor development in the intestine. These mutations disconnect the Wnt/β-catenin pathway from its Wnt extracellular signal by inactivating the APC/GSK3-β/axin destruction complex of β-catenin. This results in sustained nuclear accumulation of β-catenin, followed by β-catenin-dependent co-transcriptional activation of Wnt/β-catenin target genes. Thus, mechanisms acting downstream of APC, such as those controlling β-catenin stability and/or co-transcriptional activity, are attractive targets for CRC treatment. Protein Kinase C-α (PKCα) phosphorylates the orphan receptor RORα that then inhibits β-catenin co-transcriptional activity. PKCα also phosphorylates β-catenin, leading to its degradation by the proteasome. Here, using both in vitro (DLD-1 cells) and in vivo (C57BL/6J mice) PKCα knock-in models, we investigated whether enhancing PKCα function could be beneficial in CRC treatment. We found that PKCα is infrequently mutated in CRC samples, and that inducing PKCα function is not deleterious for the normal intestinal epithelium. Conversely, di-terpene ester-induced PKCα activity triggers CRC cell death. Together, these data indicate that PKCα is a relevant drug target for CRC treatment.

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VP-128, a novel oestradiol-platinum(II) hybrid with selective anti-tumour activity towards hormone-dependent breast cancer cells in vivo

Endocrine Related Cancer ◽

10.1677/erc-09-0113 ◽

2009 ◽

Vol 16 (4) ◽

pp. 1185-1195 ◽

Cited By ~ 29

Author(s):

Céline Van Themsche ◽

Sophie Parent ◽

Valérie Leblanc ◽

Caroline Descôteaux ◽

Anne-Marie Simard ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Nuclear Accumulation ◽

Dependent Manner ◽

Anti Tumour Activity ◽

Tumour Activity ◽

Mcf 7

We have previously reported the synthesis of VP-128, a new 17β-oestradiol (E2)-linked platinum(II) hybrid with high affinity for oestrogen receptor α (ERα). In the present study, we have investigated the anti-tumour activity of VP-128 towards breast cancer cells in vitro and in vivo. We used human ERα-positive (MCF-7) and -negative (MDA-MB-468) cells as a model for treatment with increasing doses of VP-128, cisplatin or E2 in vitro and for xenograft experiments in nude mice in vivo. Compared with cisplatin, VP-128 showed markedly improved in vitro and in vivo anti-tumour activity towards ERα-positive MCF-7 breast cancer cells, without increased systemic toxicity. In these caspase-3-deficient cells, treatment with VP-128 overcame weak cellular sensitivity to cisplatin in vitro and in vivo. In these cells, only the hybrid induced apoptosis in an ERα-dependent manner, inactivated both X-linked inhibitor of apoptosis protein and Akt, and induced selective nuclear accumulation of ERα and the expression of ER-regulated genes c-myc and tff1, which was blocked by ERα-specific antagonist ICI 282 780. In the case of ERα-negative MDA-MB-468 cells, VP-128, but not cisplatin, induced nuclear accumulation of apoptosis-inducing factor and inhibited c-myc expression. However, VP-128 did not show enhanced in vivo anti-tumour activity compared with cisplatin. These results reveal two different modes of action for VP-128 in ERα-positive and -negative breast cancer cells, and highlight the promising therapeutic value of this unique E2-platinum hybrid for selective targeting of hormone-dependent cancers.

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Regional differences in vasculotoxic effects of cyclosporin in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y95-728 ◽

1995 ◽

Vol 73 (11) ◽

pp. 1661-1668 ◽

Cited By ~ 6

Author(s):

Marleen Verbeke ◽

Leo de Ridder ◽

Johan Van de Voorde ◽

Norbert Lameire

Keyword(s):

Thoracic Aorta ◽

Abdominal Aorta ◽

Regional Differences ◽

Treatment Schedule ◽

Study Protocols ◽

Relaxation Responses ◽

Thoracic And Abdominal ◽

And Control

Studies on cyclosporin-induced vasculotoxicity often yielded discrepant results, possibly as a result of differences in study protocols. The aim of the present study was to analyse cyclosporin-induced vasculotoxicity in arteries of different size and origin. Therefore, rats were treated with cyclosporin, 20 mg∙kg−1∙day−1, by gastric gavage for 10 days. In our previous studies, this treatment schedule induced renal functional impairment in vivo and an impaired relaxation response of thoracic aortic rings in vitro. Relaxation of various arteries (thoracic and abdominal aorta and carotid, renal, and interlobar arteries) from cyclosporin-treated and control rats in response to endothelium-dependent and -independent vasodilators was analysed. The thoracic aorta showed diminished endothelium-dependent and -independent relaxations; in the abdominal aorta no impairment was observed. Moreover, the dysfunction of the thoracic aorta seemed to be homogeneous along its length and showed an abrupt termination at the level of the diaphragm. In all other segments studied, no impairment of the relaxation responses was found. A similar pattern of vascular damage was found in rats treated with a very toxic cyclosporin treatment (50 mg∙kg−1∙day−1 s.c. × 7 days). The results indicate regional differences in cyclosporin-induced vasculotoxicity. The thoracic aorta, and in view of the fall of the renal blood flow, most likely also the renal resistance vessels, could be more susceptible than other vessels to cyclosporin-induced vascular dysfunction.Key words: cyclosporin, rat, arteries, vasorelaxation.

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