ABSTRACT
Negative interaction between alleles that arise independently in diverging populations (i.e., Dobzhansky-Muller incompatibilities) can cause reduction of fitness in their hybrids. However, heterosis in hybrids can emerge if hybridization breaks down detrimental epistatic interaction within parental lineages. In this study, we examined the life-history fitness of the inter-specific F1s of two recently diverged microcrustacean species Daphnia pulex and D. pulicaria as well as intra-specific crosses of D. pulex. We identified heterosis in two out of five life-history traits in the inter-specific F1s. According to theories that heterosis can transiently emerge in early speciation, the observation of heterosis in these life-history traits suggests that there are no major genetic incompatibilities between these two species affecting these traits and that D. pulex and D. pulicaria are at an early stage of speciation.
ABSTRACT
Herein is presented a fertility-preserving approach in the management of a uterine arteriovenous malformation (AVM) resistant to endovascular management. The patient had a documented AVM and underwent 2 uterine artery embolization procedures, with subsequent recurrence of symptoms. Doppler ultrasound demonstrated recanalization of the AVM. Ultimately, laparoscopic resection of the AVM was performed after laparoscopic ligation of the uterine arteries. Postoperatively, the patient has remained asymptomatic. Laparoscopic resection of a uterine AVM may offer a fertility-preserving alternative to hysterectomy in patients in whom endovascular management has failed.
Subject(s)
Arteriovenous Malformations/therapy , Organ Sparing Treatments , Uterine Artery Embolization , Uterine Artery/surgery , Uterus , Adult , Female , Humans , Laparoscopy , Ligation , Treatment FailureABSTRACT
Aromatase inhibitors (AIs) are the most effective class of drugs in the endocrine treatment of breast cancer, with an approximate 50% treatment response rate. Our objective was to determine whether intratumoral expression levels of estrogen-related genes are predictive of AI responsiveness in postmenopausal women with breast cancer. Primary breast carcinomas were obtained from 112 women who received AI therapy after failing adjuvant tamoxifen therapy and developing recurrent breast cancer. Tumor ERα and PR protein expression were analyzed by immunohistochemistry (IHC). Messenger RNA (mRNA) levels of 5 estrogen-related genes-AKR1C3, aromatase, ERα, and 2 estradiol/ERα target genes, BRCA1 and PR-were measured by real-time PCR. Tumor protein and mRNA levels were compared with breast cancer progression rates to determine predictive accuracy. Responsiveness to AI therapy-defined as the combined complete response, partial response, and stable disease rates for at least 6 months-was 51%; rates were 56% in ERα-IHC-positive and 14% in ERα-IHC-negative tumors. Levels of ERα, PR, or BRCA1 mRNA were independently predictive for responsiveness to AI. In cross-validated analyses, a combined measurement of tumor ERα and PR mRNA levels yielded a more superior specificity (36%) and identical sensitivity (96%) to the current clinical practice (ERα/PR-IHC). In patients with ERα/PR-IHC-negative tumors, analysis of mRNA expression revealed either non-significant trends or statistically significant positive predictive values for AI responsiveness. In conclusion, expression levels of estrogen-related mRNAs are predictive for AI responsiveness in postmenopausal women with breast cancer, and mRNA expression analysis may improve patient selection.
Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Aromatase Inhibitors/pharmacology , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Nitriles/pharmacology , Triazoles/pharmacology , 3-Hydroxysteroid Dehydrogenases/genetics , 3-Hydroxysteroid Dehydrogenases/metabolism , Aldo-Keto Reductase Family 1 Member C3 , Anastrozole , Antineoplastic Agents, Hormonal/therapeutic use , Aromatase/genetics , Aromatase/metabolism , Aromatase Inhibitors/therapeutic use , BRCA1 Protein/genetics , BRCA1 Protein/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Drug Resistance, Neoplasm , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Estrogens/physiology , Female , Gene Expression Regulation, Neoplastic , Genetic Markers , Humans , Hydroxyprostaglandin Dehydrogenases/genetics , Hydroxyprostaglandin Dehydrogenases/metabolism , Letrozole , Middle Aged , Nitriles/therapeutic use , ROC Curve , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Tamoxifen/pharmacology , Tamoxifen/therapeutic use , Treatment Outcome , Triazoles/therapeutic useABSTRACT
Obesity has been associated with abnormally high expression of the enzyme aromatase in the breast, increased local estrogen production, and predisposition to breast hyperplasia and cancer. Increased adiposity in postmenopausal women may trigger signaling pathways that induce aromatase expression. In breast adipose fibroblasts, increased TNF production may induce the distal aromatase promoter, whereas increased local PGE(2) production may induce the proximal promoter region. We review here the mechanisms that control aromatase gene expression in breast adipose tissue, and the paracrine interactions between malignant breast epithelial cells and the surrounding adipose fibroblasts. Systematic characterization of these signaling pathways will facilitate the identification of potential drug targets to selectively reduce aromatase expression and excessive estrogen production, with therapeutic benefit.
Subject(s)
Aromatase/metabolism , Breast Neoplasms/pathology , Obesity/complications , Adipose Tissue/metabolism , Adipose Tissue/pathology , Aromatase/biosynthesis , Breast/metabolism , Breast/pathology , Breast Neoplasms/etiology , Breast Neoplasms/metabolism , Estrogens/biosynthesis , Female , Fibroblasts/enzymology , Humans , Obesity/physiopathology , Paracrine Communication/physiology , Signal Transduction/physiologyABSTRACT
OBJECTIVE: To evaluate the influence of "true" versus "sham" acupuncture on pregnancy rates (PRs) in women undergoing IVF. DESIGN: Randomized controlled trial, double-blinded with independent observer. SETTING: Academic infertility clinic. PATIENT(S): One hundred sixty patients <38 years old undergoing IVF with or without intracytoplasmic sperm injection. INTERVENTION(S): Subjects were randomly allocated to the true or sham group and underwent acupuncture 25 minutes before and after ET. Subjects completed a McGill Pain Questionnaire regarding their clinical symptoms during ET. MAIN OUTCOME MEASURE(S): Clinical PR and clinical symptoms during ET. RESULT(S): While the overall clinical PR was 51.25%, there was no significant difference between the arms of the study (true = 45.3% vs. sham = 52.7%); 33.1% of the patients had ultrasound-documented singleton pregnancy, and 15% of patients had twin gestations, while one patient in the true arm had a triplet gestation. There were significant differences in the subjective, affective, and total pain experience between both arms. The subjects in the true arm described their acupuncture session as being more "tiring" and "fearful" and experienced more "achiness" compared with their sham counterparts. CONCLUSION(S): There was no statistically significant difference in the clinical or chemical PRs between both groups. Patients undergoing true acupuncture had differing sensory experiences compared with patients in the sham arm. There were no significant adverse effects observed during the study, suggesting that acupuncture is safe for women undergoing ET.
