Relationship between the Number of Homoeologues, Chiasma Frequency and the Frequency of Telosome Pairing in Wheat

Pairing frequencies of a single telosome in groups of two, three, four, five and six equally related homoeologues were calculated for a range of values of c (the ratio of actual chiasma frequency to the total possible number of chiasmata, as described by Driscoll, Bielig and Darvey 1979). At low c values, the frequency of telosome pairing is little affected by the number of homoeologues. At high c values, the frequency is little affected by the number of homoeolgues if the number is even; if the number is odd, the frequency is dependent on the number of homoeologues and increases with increasing numbers of homoeologues. At intermediate c values, the pairing frequency is dependent on the number of homoeologues for both even and odd numbers of homoeologues.     

Therapy for Cancer of the Breast: Current Status of Steroid Hormone Receptors

Estrogen receptor (ER) assays in human breast cancer tissue have proved useful in selecting patients for endocrine therapies. The absence of ER indicates hormone independent tumors and precludes the use of endocrine therapy. Patients with positive tumor ER respond to endocrine therapy at nearly twice the rate of those patients chosen by clinical criteria, although about a third of ER positive tumors in patients still do not respond. Recently, research has been directed toward increasing the accuracy of the ER assay in the ER positive group. The absolute tumor ER value and the presence of progesterone receptor appear promising in this regard. The significance of nuclear estrogen receptor is being studied. Finally, the ER status of a primary breast tumor appears to be a marker for the length of time until recurrence after mastectomy, and for survival. The ER assay may prove valuable in planning new adjuvants in the treatment of breast cancer.     

Iodohexestrols. II. Characterization of the binding and estrogenic activity of iodinated hexestrol derivatives, in vitro and in vivo.

The affinity of ortho-iodinated hexestrols for the estrogen binding protein from rat uterus, determined by competitive binding assay, decreases with progressive iodine substitution; 3-iodohexestrol (I-Hex) has a binding affinity 42% that of estradiol. Analysis of [3-H]-I-Hex binding in rat uterine cytosol by sucrose density gradient centrifugation shows both an estrogen-specific binding component (8 S) and a more abundant component (4 S) that is not estrogen specific. Scatchard analysis indicates that this latter binding is of high affinity (Kd equals to 3.7-8.3 times 10- minus-9 M) but is not uterine specific. Polyacrylamide gel electrophoresis shows that most of the [3-H]-I-Hex binding activity in serum and uterine cytosol is distinct from and anodic to the principal protein component (albumin), and that is comigrates with [14-C]thyroxine binding activity. In in vitro incubation of rat uteri, I-Hex can block the specific uptake of [3-H]estradiol into the nuclear fraction; it itself causes a translocation of estrogen-specific binding capacity (as measured by exchange) from cytoplasm to nuclei, and can induce the synthesis of an estrogen-specific uterine protein, all under conditions where it is not metabolically deiodinated to hexestrol. The uterotrophic activities of the iodohexestrols are in most cases comparable to that expected on the basis of their competitive binding affinities. However, selective, estrogen-specific uptake of [3-H]-I-Hex into rat uterus, either in vitro or in vivo, cannot be demonstrated.     

Steroids and human breast cancer.

Normal mammary gland cells are sensitive to a number of hormones, of which estrogen and prolactin exert the most obvious effects. Some breast cancer cells are also sensitive. Cytoplasmic receptor sites for each hormone are responsible for the interaction between the hormone and the cell. The presence of estrogen receptor has been especially studied in humans. Data collected from several sources are reviewed. The prese nce of estrogen receptors has been assayed in 154 primary breast tumors and 72 metastatic breast tumors for correlation with response to endocri ne therapy. Positive values were found in 70% of primary and 58% of metastatic specimens. Of 211 treatment trials, ablative therapy produced objective tumor regressions in 33%. Of the 94 trials with negative receptor values, only 8 were successful while 59 of the 107 trials in patients with positive receptor values succeeded. In those with borderline tumor receptor, values had a 30% response. With additive therapy, 34% of 170 trials showed tumor regression. Of these, 82 had negat ive receptor values but 8% were successful, whereas of 85 with positive receptor values, 60% were favorable. With miscellaneous therapy, 27% of 55 trials gave responses to a variety of endocrine therapies, including antiestrogens. The 32 with negative receptor values gave 16% of favorable responses whereas 43% of 23 trials in those with positive receptor values succeeded. Estrogen receptor assays performed routinely would spare patients with negative results from unnecessary major ablative therapy. Of those with positive findings, 55-60% might be benefited. The fact that all with positive receptor values do not respond is attributed to the fact that this is only part of the hormonal control system. Other biochemical lesions are assumed to have occurred in patients when endocrine therapy fails despite positive estrogen receptor levels as measured.     

MCF-7; a human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors.

We have identified receptors for glucocorticoids, progestins, and androgens in a human breast tumor cell line (MCF-7) known to have estrogen receptor. Sucrose density gradients show that MCF-7 cytosol contains approximately 100 fm/mg protein estradiol (E2-3H) receptor, more than 300 fm/mg protein progesterone receptor (measured with R5020-3H), about 40 fm/mg protein 5alpha-dihydrotestosterone (5alpha-DHT-3H) receptor, and 800 fm/mg glucocorticoid receptor (measured with dexamethasone-3H). Dissociation constants obtained by Scatchard analyses were approximately 0.6 x 10(-10)M (E2), 1 x 10(-9)M (R5020), 2.8 x 10(-10)M (5alpha-DHT) and 8 x 10(-9)M (dexamethasone). No cross competition was found for estrogen receptor, but progestins competed for androgen and glucocorticoid binding. The androgen, but not the glucocorticoid, partially competed for R5020 binding to progesterone receptor. This first demonstration of 4 classes of steroid receptors in human breast cancer means that MCF-7 may be an excellent in vitro model for studying the mechanism of tumor response to endocrine therapy as well as the complex relationships between binding and biological actions of these hormones.     

Ovarian and adrenal function during the estrous cycle of the sow.

The concentrations of plasma estrogens, progesterone, and corticosteroids and of urinary pregnanediol, pregnanetriol, ketogenic steroids, and corticosteroids were determined as indicators of ovarian and adrenal function throughout a normal sow's estrous cycle. Two broad peaks of plasma estrogen, one lasting 11–12 days during estrus and another 6-day peak period during the early part of the luteal phase were detected. Plasma progesterone was elevated during the late follicular and luteal phase. Two broad peaks of plasma corticoids appeared, one following the decrease of plasma progesterone and the second 7–14 days later. Those elevations in plasma corticoids occurred when estrogen titres were elevated. Urinary determinations generally reflected plasma findings. Estrogen levels began to rise during the follicular phase while a reasonably high progesterone level was evident. Estrogen titres never decreased to non-detectable levels. An interrelationship between adrenal function and ovarian estrogen production is suggested.     

Prostaglandin synthesis by rheumatoid synovium and its stimulation by colchicine

The synthesis of prostaglandins by rheumatoid synovial tissue in organ culture was studied utilizing radioimmunoassay, with antisera to PGB₁, PGF_1α and PGF_2α. It was established that PGE₂ and PGF_2α were the major prostaglandins formed by analyses of culture media with the two antisera to PGF, before and after alkali treatment. Indomethacin at 5 μg/ml suppressed prostaglandin synthesis, usually to <1% of control cultures. Colchicine, 0.1 μg/ml resulted in marked stimulation of prostaglandin synthesis, in some cases over 10 fold. It is suggested, because of the colchicine effect, that the state of the microtubules may regulate the rate of prostaglandin biosynthesis. It is possible that prostaglandin E₂ produced by rheumatoid synovia may contribute to the pathogenesis of the inflammatory reaction and lead to destruction of juxta-articular bone in rheumatoid arthritis.     

Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?

Melanoma, as for many other cancers, undergoes a selection process during progression that limits many innate and adaptive tumor control mechanisms. Immunotherapy with immune checkpoint blockade overcomes one of the escape mechanisms but if the tumor is not eliminated other escape mechanisms evolve that require new approaches for tumor control. Some of the innate mechanisms that have evolved against infections with microorganisms and viruses are proving to be active against cancer cells but require better understanding of how they are activated and what inhibitory mechanisms may need to be targeted. This is particularly so for inflammasomes which have evolved against many different organisms and which recruit a number of cytotoxic mechanisms that remain poorly understood. Equally important is understanding of where these mechanisms will fit into existing treatment strategies and whether existing strategies already involve the innate killing mechanisms.     

A SNP-based genetic dissection of versatile traits in bread wheat (Triticum aestivum L.)

The continuous increase in global population prompts increased wheat production. Future wheat (Triticum aestivum L.) breeding will heavily rely on dissecting molecular and genetic bases of wheat yield and related traits which is possible through the discovery of quantitative trait loci (QTLs) in constructed populations, such as recombinant inbred lines (RILs). Here, we present an evaluation of 92 RILs in a bi-parental RIL mapping population (the International Triticeae Mapping Initiative Mapping Population [ITMI/MP]) using newly generated phenotypic data in 3-year experiments (2015), older phenotypic data (1997–2009), and newly created single nucleotide polymorphism (SNP) marker data based on 92 of the original RILs to search for novel and stable QTLs. Our analyses of more than 15 unique traits observed in multiple experiments included analyses of 46 traits in three environments in the USA, 69 traits in eight environments in Germany, 149 traits in 10 environments in Russia, and 28 traits in four environments in India (292 traits in 25 environments) with 7584 SNPs (292 × 7584 = 2 214 528 data points). A total of 874 QTLs were detected with limit of detection (LOD) scores of 2.01–3.0 and 432 QTLs were detected with LOD > 3.0. Moreover, 769 QTLs could be assigned to 183 clusters based on the common markers and relative proximity of related QTLs, indicating gene-rich regions throughout the A, B, and D genomes of common wheat. This upgraded genotype–phenotype information of ITMI/MP can assist breeders and geneticists who can make crosses with suitable RILs to improve or investigate traits of interest.