Protocol for long-term treatment of lowly aggressive cancer cell lines with low concentrations of anti-tumor drugs.

The understanding of anti-tumor drug effects requires specific experimental settings which model clinical scenarios. We describe a protocol for 10-day treatment of lowly aggressive tumor cell lines with antineoplastic agents at concentrations which do not affect cell growth. We describe steps for seeding cells and treating cells with anti-tumor drugs.

Specific cellular microenvironments for spatiotemporal regulation of StAR and steroid synthesis.

For many years, research in the field of steroid synthesis has aimed to understand the regulation of the rate-limiting step of steroid synthesis, i.e. the transport of cholesterol from the outer to the inner mitochondrial membrane, and identify the protein involved in the conversion of cholesterol into pregnenolone.

Exposure to anticancer drugs modulates the expression of ACSL4 and ABCG2 proteins in adrenocortical carcinoma cells.

Adrenocortical carcinoma (ACC) is a rare and malignant disease, with more than 50 % of patients developing hormone-secreting tumors. These tumors are genetically heterogeneous and potentially lethal, as metastasis is often underway at the time of diagnosis. While chemoresistance can be multifactorial, Acyl CoA synthetase 4 (ACSL4) is known to contribute to the generation of highly aggressive cellular phenotypes, while increased expression and activity of multidrug transporters such as ATP-binding cassette subfamily G member 2 (ABCG2) are known to play a key role.

Impact of dietary analyzed calcium to phosphorus ratios and standardized total tract digestible phosphorus to net energy ratios on growth performance, bone, and carcass characteristics of pigs.

A total of 2,184 pigs (337 × 1,050, PIC; initially 12.4 ± 0.17 kg) were used in a 143-d study to evaluate the effects of feeding varying analyzed calcium to phosphorus ratios (Ca:P) at two standardized total tract digestible (STTD) phosphorus to net energy ratios (STTD P:NE).

Effects of dietary carnitine supplementation on semen output and quality of boars.

Carnitine is an amino acid derivative that performs the functions of increasing energy production as well as acting as an antioxidant for sperm cells. This study was conducted to investigate the effects of the inclusion of carnitine in boar diets on semen output and quality. Sixty-four purebred and hybrid boars at a commercial boar stud were blocked by age and semen quality and randomly allotted to receive a daily 30 g top-dress of either soybean meal (CON) or soybean meal and 625 mg of L-Carnitine (CARN).

Optimal Standardized Ileal Digestible Total Sulfur Amino Acids to Lysine REQUIREMENTS Are Increased in Nursery Pigs Raised under Antibiotic-Free Feeding Regime.

This study aimed to investigate the effect of increasing the standardized ileal digestible (SID) total sulfur amino acid to lysine (TSAA:Lys) on the growth performance of nursery pigs raised with or without antibiotics (AGP) and to determine the optimal SID TSAA:Lys in nursery pigs raised without AGP. In Exp. 1, 924 nursery pigs (7.

New inhibitor targeting Acyl-CoA synthetase 4 reduces breast and prostate tumor growth, therapeutic resistance and steroidogenesis.

Acyl-CoA synthetase 4 (ACSL4) is an isoenzyme of the fatty acid ligase-coenzyme-A family taking part in arachidonic acid metabolism and steroidogenesis. ACSL4 is involved in the development of tumor aggressiveness in breast and prostate tumors through the regulation of various signal transduction pathways. Here, a bioinformatics analysis shows that the ACSL4 gene expression and proteomic signatures obtained using a cell model was also observed in tumor samples from breast and cancer patients.

Effects of different amounts and type of diet during weaning-to-estrus interval on reproductive performance of primiparous and multiparous sows.

During weaning-to-estrus interval (WEI), the sows are usually fed with high feed level to improve the reproductive performance. However, the WEI has been reduced over the years which may reduce the impact of feed level on performance in the modern genetic lines. The aim of this study was to evaluate the effect of two feeding levels (moderate feeding level (MFL): 2.

Impact of feed intake in early gestation on maternal growth and litter size according to body reserves at weaning of young parity sows.

The effect of increasing the feed level (1.8, 2.5, and 3.

Impact of increasing weaning age on pig performance and belly nosing prevalence in a commercial multisite production system.

The effects of increasing weaning age in a commercial production system on nursery and finishing performance were evaluated. A total of 1,176 pigs (PIC 337 × Camborough) were used in a 136-d growth trial with 14 and 10 replications/weaning age on the nursery and finishing phases, respectively. Treatments included weaning litters at 19, 22, 25, or 28 d of age.

Maternal nutrition during early and late gestation in gilts and sows under commercial conditions: impacts on maternal growth and litter traits1.

The effects of two different feeding levels, offered in two phases during gestation, on body measurements and litter traits were evaluated in 152 gilts and 551 sows. The treatments consisted of the combination of two gestation phases (phase 1-days 22 to 42; phase 2-days 90 to 110) and two feed amounts (1.8 or 3.

Impact of housing nursery pigs according to body weight on the onset of feed intake, aggressive behavior, and growth performance.

Housing nursery pigs according to body weight is an observed common practice in production systems and, supposedly, improves growth performance and reduces body weight (BW) variation. This 42-day study evaluated the effects of housing nursery pigs according to BW on performance, onset of feed intake, and aggressive behavior. A total of 504 pigs were ranked by BW at weaning and categorized into three groups of 168 pigs each: light, medium, and heavy.

Calcium to phosphorus ratio requirement of 26- to 127-kg pigs fed diets with or without phytase1,2.

Two experiments were conducted to determine the effects of calcium to phosphorus (Ca:P) ratio in diets adequate in standardized total tract digestible (STTD) P on performance of 26- to 127-kg pigs fed diets with or without phytase. Pens of pigs (n = 1,134 in Exp. 1 and n = 1,215 in Exp.

Standardized total tract digestible phosphorus requirement of 24- to 130-kg pigs1,2.

A study was conducted to determine the standardized total tract digestible phosphorus (STTD P) requirement for 24- to 130-kg finishing pigs housed under commercial conditions. A total of 1,130 barrows and gilts (PIC 359 × 1050, Hendersonville, TN; initially 24.2 kg) were used, with 26 to 27 pigs per pen with 7 replicates per treatment.

Effects of standardized total tract digestible phosphorus on growth performance of 11- to 23-kg pigs fed diets with or without phytase1,2.

Two experiments were conducted to determine the standardized total tract digestible phosphorus (STTD P) requirement for 11- to 23-kg nursery pigs fed diets with or without phytase. A total of 1,080 and 2,140 pigs (PIC 359 × Camborough, Hendersonville, TN; initially 11.4 ± 0.

Regulatory mechanisms leading to differential Acyl-CoA synthetase 4 expression in breast cancer cells.

Acyl-CoA synthetase 4 (ACSL4) overexpression plays a causal role in the aggressiveness of triple negative breast cancer. In turn, a negative correlation has been established between ACSL4 and estrogen receptor alpha (ERα) expression. However, the upstream regulatory mechanisms leading to differential ACSL4 expression between triple negative breast cancer and ERα-positive cells remained unknown.

Evaluation of the optimal standardized ileal digestible threonine:lysine ratio in lactating sow diets.

Camborough PIC sows (n = 291) were fed 1 of 5 dietary treatments to evaluate the standardized ileal digestible (SID) Thr:Lys requirement during lactation. Sows were blocked by parity (1, 2, and 3+) and randomly allotted to 1 of 5 SID Thr:Lys ratios (52, 60, 68, 76, and 84). SID Lys was formulated to 1.

Evaluation of the optimal standardized ileal digestible valine:lysine ratio in lactating sow diets1.

An experiment was conducted with 430 sows to evaluate the ideal standardized ileal digestible (SID) Val:Lys on sow and litter performance during an 18.6-d lactation period. The SID Val:Lys ratios measured were based on the previously published literature and then values above and below reported values.

Impact of feed intake during late gestation on piglet birth weight and reproductive performance: a dose-response study performed in gilts.

The effects of increasing feed intake (1.8, 2.3, 2.

Acyl-CoA synthetase-4 is implicated in drug resistance in breast cancer cell lines involving the regulation of energy-dependent transporter expression.

Acyl-CoA synthetase-4 (ACSL4) is an enzyme implicated in estrogen receptor α (ERα) negative regulation and hormone therapy resistance in breast cancer. In addition, ACSL4 has been associated to certain types of hormone resistance in prostate cancer. Chemotherapeutic treatment of disseminated breast cancer is usually faced with therapy resistance associated to ATP-binding cassette (ABC) transporter expression, which detect and eject anti-cancer drugs from cells.

Role of Protein Phosphorylation and Tyrosine Phosphatases in the Adrenal Regulation of Steroid Synthesis and Mitochondrial Function.

In adrenocortical cells, adrenocorticotropin (ACTH) promotes the activation of several protein kinases. The action of these kinases is linked to steroid production, mainly through steroidogenic acute regulatory protein (StAR), whose expression and activity are dependent on protein phosphorylation events at genomic and non-genomic levels. Hormone-dependent mitochondrial dynamics and cell proliferation are functions also associated with protein kinases.

Acyl-CoA synthetase-4, a new regulator of mTOR and a potential therapeutic target for enhanced estrogen receptor function in receptor-positive and -negative breast cancer.

Although the role of acyl-CoA synthetase 4 (ACSL4) in mediating an aggressive phenotype is well accepted, there is little evidence as to the early steps through which ACSL4 increases tumor growth and progression. In this study, and by means of the stable transfection of MCF-7 cells with ACSL4 using the tetracycline Tet-Off system (MCF-7 Tet-Off/ACSL4), we identify the mTOR pathway as one of the main specific signatures of ACSL4 expression and demonstrate the partial involvement of the lipoxygenase pathway in the activation of mTOR. The specificity of ACSL4 action on mTOR signaling is also determined by doxycycline inhibition of ACSL4 expression in MCF-7 Tet-Off/ACSL4 cells, by the expression of ACSL4 in the non-aggressive T47D breast cancer cell line and by knocking down this enzyme expression in the MDA-MB-231 breast cancer cells, which constitutively express ACSL4.

The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models.

Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer.

The role of mitochondrial fusion and StAR phosphorylation in the regulation of StAR activity and steroidogenesis.

The steroidogenic acute regulatory (StAR) protein regulates the rate-limiting step in steroidogenesis, i.e. the delivery of cholesterol from the outer (OMM) to the inner (IMM) mitochondrial membrane.

Characterization of the mouse promoter region of the acyl-CoA synthetase 4 gene: role of Sp1 and CREB.

Acyl-CoA synthetase 4 (Acsl4) is involved in several cellular functions including steroidogenesis, synaptic development and cancer metastasis. Although the expression of Acsl4 seems to be regulated by tissue- and cell-specific factors as well as pituitary hormones and growth factors, the transcriptional mechanisms involved remain unknown. We demonstrated hCG and cAMP regulation of Acsl4 mRNA in mouse steroidogenic MA-10 Leydig cells.