Plasma microRNA signatures predict prognosis in canine osteosarcoma patients.

Appendicular central osteosarcoma (OSA) is a common and highly aggressive tumour in dogs. Metastatic disease to the lungs is common and even with chemotherapy the prognosis is generally poor. However, few cases survive well beyond reported median survival times.

Quantitative intravital imaging for real-time monitoring of pancreatic tumor cell hypoxia and stroma in an orthotopic mouse model.

Pancreatic cancer is a lethal disease with few successful treatment options. Recent evidence demonstrates that tumor hypoxia promotes pancreatic tumor invasion, metastasis, and therapy resistance. However, little is known about the complex relationship between hypoxia and the pancreatic tumor microenvironment (TME).

Ceramide-Induced Lysosomal Biogenesis and Exocytosis in Early-Onset Preeclampsia Promotes Exosomal Release of SMPD1 Causing Endothelial Dysfunction.

Aberrant ceramide build-up in preeclampsia, a serious disorder of pregnancy, causes exuberant autophagy-mediated trophoblast cell death. The significance of ceramide accumulation for lysosomal biogenesis in preeclampsia is unknown. Here we report that lysosome formation is markedly increased in trophoblast cells of early-onset preeclamptic placentae, in particular in syncytiotrophoblasts.

Differential effects of the 1,25D3-MARRS receptor (ERp57/PDIA3) on murine mammary gland development depend on the vitamin D3 dose.

1,25 dihydroxyvitamin D3 (1,25D3) is the most potent biologically active form of vitamin D3. Its actions on the mammary gland include cell growth inhibition and anti-cancer effects. This study's purpose was to explore the role of the 1,25D3-membrane associated rapid response steroid (MARRS) receptor in the mammary gland using a tissue-specific knockout mouse model and a vitamin D3 dietary intervention.

Reirradiation of Head and Neck Cancers With Intensity Modulated Radiation Therapy: Outcomes and Analyses.

Purpose: To review our 15-year institutional experience using intensity modulated radiation therapy (IMRT) to reirradiate patients with head and neck squamous cell carcinomas (HNSCC) and identify predictors of outcomes and toxicity.

Methods And Materials: We retrospectively reviewed the records of 227 patients who received head and neck reirradiation using IMRT from 1999 to 2014. Patients treated with noncurative intent were excluded.

Improved setup and positioning accuracy using a three-point customized cushion/mask/bite-block immobilization system for stereotactic reirradiation of head and neck cancer.

The purpose of this study was to investigate the setup and positioning uncertainty of a custom cushion/mask/bite-block (CMB) immobilization system and determine PTV margin for image-guided head and neck stereotactic ablative radiotherapy (HN-SABR). We analyzed 105 treatment sessions among 21 patients treated with HN-SABR for recurrent head and neck cancers using a custom CMB immobilization system. Initial patient setup was performed using the ExacTrac infrared (IR) tracking system and initial setup errors were based on comparison of ExacTrac IR tracking system to corrected online ExacTrac X-rays images registered to treatment plans.

Outcomes for hypopharyngeal carcinoma treated with organ-preservation therapy.

Background: This study assessed outcomes of patients with hypopharyngeal carcinoma treated with organ-preservation therapy utilizing intensity-modulated radiation therapy (IMRT).

Methods: The medical records of 98 patients treated with definitive IMRT +/- chemotherapy from 2001 to 2013 for nonmetastatic hypopharyngeal cancer were retrospectively reviewed.

Results: Patients were treated to doses of 66 to 72 Gy.

Prognosis for patients with metastatic breast cancer who achieve a no-evidence-of-disease status after systemic or local therapy.

Background: This study sought to determine outcomes for patients with metastatic breast cancer (MBC) with no evidence of disease (NED) after treatment and to identify factors predictive of outcomes once the status of NED was attained.

Methods: This study reviewed 570 patients with MBC who were consecutively treated between January 2003 and December 2005. Ninety patients (16%) attained NED, which was defined as a complete metabolic response on positron emission tomography or sclerotic healing of bone metastases on computed tomography or magnetic resonance imaging.

Orbital carcinomas treated with adjuvant intensity-modulated radiation therapy.

Background: The purpose of this study was to assess outcomes of patients with orbital carcinomas treated with orbital exenteration and intensity-modulated radiation therapy (IMRT).

Methods: Twenty-nine patients were treated with orbital exenteration and postoperative IMRT between 2002 through 2011; their medical records were retrospectively reviewed.

Results: Adenoid cystic carcinoma represented the most common histology (41%) followed by squamous cell carcinoma (21%).

Outcomes After Surgery and Radiotherapy for Papillary Tumor of the Pineal Region.

Background: Papillary tumor of the pineal region (PTPR) is a rare neuroectodermal tumor that was first described in 2003 and formally codified by the World Health Organization in 2007. Limited reports suggest surgical resection is the mainstay of treatment; however, the role of multimodality therapy is not well defined. We evaluated our institutional experience in the treatment of PTPR.

Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans.

Implantation of a blastocyst in the uterus is a multistep process tightly controlled by an intricate regulatory network of interconnected ovarian, uterine, and embryonic factors. Bone morphogenetic protein (BMP) ligands and receptors are expressed in the uterus of pregnant mice, and BMP2 has been shown to be a key regulator of implantation. In this study, we investigated the roles of the BMP type 1 receptor, activin-like kinase 2 (ALK2), during mouse pregnancy by producing mice carrying a conditional ablation of Alk2 in the uterus (Alk2 cKO mice).

Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function.

The transforming growth factor β (TGFβ) superfamily proteins are principle regulators of numerous biological functions. Although recent studies have gained tremendous insights into this growth factor family in female reproduction, the functions of the receptors in vivo remain poorly defined. TGFβ type 1 receptor (TGFBR1), also known as activin receptor-like kinase 5, is the major type 1 receptor for TGFβ ligands.

Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development.

Bone morphogenetic proteins (BMPs) have diverse roles in development and reproduction. Although several BMPs are produced by oocytes, thecal cells, and granulosa cells of developing follicles, the in vivo functions of most of these ligands are unknown. BMP signals are transduced by multiple type I and type II TGFbeta family receptors, and of the type I receptors, BMP receptor 1A (BMPR1A) and BMP receptor 1B (BMPR1B) are known to be expressed in rodent granulosa cells.

TEX14 interacts with CEP55 to block cell abscission.

In somatic cells, abscission, the physical separation of daughter cells at the completion of cytokinesis, requires CEP55, ALIX, and TSG101. In contrast, cytokinesis is arrested prior to abscission in differentiating male germ cells that are interconnected by TEX14-positive intercellular bridges. We have previously shown that targeted deletion of TEX14 disrupts intercellular bridges in all germ cells and causes male sterility.

Deletion of the novel oocyte-enriched gene, Gpr149, leads to increased fertility in mice.

Through in silico subtraction and microarray analysis, we identified mouse Gpr149, a novel, oocyte-enriched transcript that encodes a predicted orphan G-protein-coupled receptor (GPR). Phylogenetic analysis of GPR149 from fish to mammals suggests that it is widely conserved in vertebrates. By multitissue RT-PCR analysis, we found that Gpr149 is highly expressed in the ovary and also in the brain and the digestive tract at low levels.

The mammalian ovary from genesis to revelation.

Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis.

Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15.

Oocyte-derived growth factors are critically involved in multiple ovarian processes via paracrine actions. Although recombinant proteins have been applied to dissect the physiological functions of these factors, variation of activities among different protein preparations remains an issue. To further elucidate the roles of one of these growth factors, bone morphogenetic protein 15 (BMP15), in mediating oocyte-regulated molecular and cellular events and to explore its potential clinical application, we engineered the human BMP15 sequence to efficiently produce bioactive recombinant human BMP15 (rhBMP15).

Initial report on intravesical administration of N-trifluoroacetyladriamycin-14-valerate (AD 32) to patients with refractory superficial transitional cell carcinoma of the urinary bladder.

Objectives: This study was designed to assess the pharmacokinetics, safety, and antitumor activity of intravesically administered AD 32, a novel anthracycline, in patients with transitional cell carcinoma (TCC) of the bladder.

Methods: Six weekly doses of AD 32 (200 to 900 mg) were administered to 32 patients with superficial TCC who were candidates for intravesical treatment. Serum drug levels were measured during the 6-hour period after administration of the first, third, and sixth doses.

A pregnant pause: blunt urologic trauma in a young woman.

Trauma in a woman of child-bearing age is rarely discussed in urologic literature. However, it is the leading cause of maternal death during pregnancy. We propose that the standard workup for gross hematuria secondary to trauma be performed, in light of child-bearing age, since the greatest cause of fetal demise in this setting is maternal death.

Successful renal autotransplantation in a patient with bilateral renal artery thrombosis.

Bilateral renal artery thrombosis is a rare but traumatic injury that is most commonly caused by sudden deceleration. Traditional methods of repair (e.g.

Experience with schistosomiasis in renal transplantation.

Schistosomiasis involving the urinary tract has only occasionally been reported in North American literature and rarely from American hospital experience. Chronic infection may result in numerous abnormalities of the urinary tract which may interfere with the function of a transplanted kidney. Our institution has performed a number of renal transplants in patients who are from countries where schistosomiasis is endemic.

Combined retrograde-antegrade ureteral stent passage: salvage procedure for a ureteral leak.

The authors describe a stent placement procedure for treatment of an infected ureteral leak after failure of traditional antegrade and retrograde approaches. In this procedure, a guide wire was placed across the distal ureteral segment into a urinoma with use of cystoscopic guidance. Thereafter, an antegrade approach was used to pass a wire loop snare, capture the guide wire, and withdraw it through the proximal ureter for subsequent stent passage.