Transmembrane prostatic acid phosphatase: a therapeutic target in advanced prostate cancer.

Prostate cancer (PCa) is the most common cancer and second leading cause of cancer death in American men. Most patients with metastatic disease respond initially to androgen deprivation therapy (ADT), but almost inevitably progress to castration resistant prostate cancer (CRPC). Identification of markers and drivers of mCRPC that (a) represent a progenitor-type cancer cell population (b) persist in castration resistant disease (c) are actionable targets expressed on the cell surface, and (d) are induced by hypoxia, is required to facilitate the development of novel targeted therapies.

Nitinol Compression Staple Versus Headless Compression Screw Fixation for Scaphoid Waist Fractures.

Background: There are a variety of ways to surgically manage patients with scaphoid waist fractures. The purpose of this study is to compare the rate of union achieved with a nitinol compression staple versus that of a headless compression screw in the treatment of scaphoid waist fractures.

Methods: We performed a retrospective review of patients with middle-third scaphoid fractures treated surgically.

Scaphoid Fractures Requiring Bone Graft: Does Graft Source Matter?

Background: Treatment of scaphoid fractures often requires bone grafting. In such cases, bone graft is traditionally harvested from the iliac crest, but utilizing the distal radius carries less morbidity and is becoming more popular. The purpose of this study is to compare the outcomes of treatment of scaphoid waist fractures with the use of distal radius and iliac crest bone grafts.

Cooperativity of c-MYC with Krüppel-Like Factor 6 Splice Variant 1 induces phenotypic plasticity and promotes prostate cancer progression and metastasis.

Metastasis remains a major cause of morbidity and mortality in men with prostate cancer, and the functional impact of the genetic alterations, alone or in combination, driving metastatic disease remains incompletely understood. The proto-oncogene c-MYC, commonly deregulated in prostate cancer. Transgenic expression of c-MYC is sufficient to drive the progression to prostatic intraepithelial neoplasia and ultimately to moderately differentiated localized primary tumors, however, c-MYC-driven tumors are unable to progress through the metastatic cascade, suggesting that a "second-hit" is necessary in the milieu of aberrant c-MYC-driven signaling.

Reducing patient surge: community based social networks as first responders.

A major challenge for health services worldwide is in providing adequate medical care during mass disasters. The ongoing COVID-19 pandemic highlights this difficulty. Patient surge, a consequence of most types of disasters that contribute to trauma experiences, is a primary factor in disrupting such care as it is composed of worried well persons and those experiencing psychosocial trauma that can severely disrupt and overwhelm effective acute hospital based health care.

The Use of Nitinol Compression Staple Fixation and Bone Graft for Scaphoid Waist Fractures and Nonunion: A Surgical Technique.

In the management of scaphoid fractures, nonunion is an important complication that can lead to carpal instability and early-onset arthritis. Various techniques have been described to treat scaphoid nonunions, yet a clear consensus on the superiority of one method is not yet established. The use of compression staple fixation has been described in the literature and may be a viable alternative to other fixation techniques.

Using 360-Degree Video as a Research Stimulus in Digital Health Studies: Lessons Learned.

Due to the accessibility of omnidirectional cameras to record 360-degree videos and the technology to view the videos via mobile phones and other devices, 360-degree videos are being used more frequently to place people in different contexts and convey health-related information. Increasingly, 360-degree videos are being employed in health marketing because they have the potential to enhance health-related attitudes and behaviors. As a case study on how this technology may be used for health-related information and its effect on health care providers, we created a 360-degree video that portrays the experience of a migraine sufferer to be used as a stimulus in an online study.

Papillary urothelial carcinoma of the vagina: A case presentation and review of the literature.

A 92-year-old woman with history of right nephroureterectomy for low grade Ta urothelial carcinoma (UC) of the renal pelvis and proximal ureter and high grade Ta and carcinoma-in-situ of the bladder presented for surveillance cystoscopy in 2019. She was found to have no evidence of disease within bladder or upper tract, however demonstrated a large papillary lesion within the vagina. This lesion stained for p40+, p16 patchy+, and GATA3+, all markers of UC, and the same molecular makeup of her prior bladder tumor.

Mechanisms of Osteoblastic Bone Metastasis in Prostate Cancer: Role of Prostatic Acid Phosphatase.

Prostate cancer (PCa) preferentially metastasizes to bone, leading to complications including severe pain, fractures, spinal cord compression, bone marrow suppression, and a mortality of ∼70%. In spite of recent advances in chemo-, hormonal, and radiation therapies, bone-metastatic, castrate-resistant PCa is incurable. PCa is somewhat unique among the solid tumors in its tendency to produce osteoblastic lesions composed of hypermineralized bone with multiple layers of poorly organized type I collagen fibrils that have reduced mechanical strength.

Small-Molecule Activators of Protein Phosphatase 2A for the Treatment of Castration-Resistant Prostate Cancer.

Primary prostate cancer is generally treatable by androgen deprivation therapy, however, later recurrences of castrate-resistant prostate cancer (CRPC) that are more difficult to treat nearly always occur due to aberrant reactivation of the androgen receptor (AR). In this study, we report that CRPC cells are particularly sensitive to the growth-inhibitory effects of reengineered tricyclic sulfonamides, a class of molecules that activate the protein phosphatase PP2A, which inhibits multiple oncogenic signaling pathways. Treatment of CRPC cells with small-molecule activators of PP2A (SMAP) decreased cellular viability and clonogenicity and induced apoptosis.

Prostatic Acid Phosphatase Alters the RANKL/OPG System and Induces Osteoblastic Prostate Cancer Bone Metastases.

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization.

Metastatic Malignant Melanoma to Urinary Bladder: A Potential Pitfall for High-Grade Urothelial Carcinoma.

We present a case of a 61-year-old female presenting with a bladder tumor that occurred 7 years after her previous diagnosis of Clark's level III mid-back melanoma. The bladder tumor was submitted to histopathology without accompanying clinical history, and an initial diagnosis of high-grade urothelial carcinoma was rendered based on epithelioid and sarcomatoid appearing pleomorphic histopathology. We present this case to highlight the diagnostic challenge presented by the rare occurrence of metastatic melanoma to the urinary bladder and the potential pitfall of this lesion being diagnosed as high-grade urothelial carcinoma in the presence of limited clinical history.

Androgens up-regulate transcription of the Notch inhibitor Numb in C2C12 myoblasts via Wnt/β-catenin signaling to T cell factor elements in the Numb promoter.

Androgen signaling via the androgen receptor is a key pathway that contributes to development, cell fate decisions, and differentiation, including that of myogenic progenitors. Androgens and synthetic steroids have well established anabolic actions on skeletal muscle. Wnt and Notch signaling pathways are also essential to myogenic cell fate decisions during development and tissue repair.

KLF6-SV1 drives breast cancer metastasis and is associated with poor survival.

Metastasis is the major cause of cancer mortality. A more thorough understanding of the mechanisms driving this complex multistep process will aid in the identification and characterization of therapeutically targetable genetic drivers of disease progression. We demonstrate that KLF6-SV1, an oncogenic splice variant of the KLF6 tumor suppressor gene, is associated with increased metastatic potential and poor survival in a cohort of 671 lymph node-negative breast cancer patients.

Nandrolone, an anabolic steroid, stabilizes Numb protein through inhibition of mdm2 in C2C12 myoblasts.

Nandrolone, an anabolic steroid, slows denervation atrophy of rat muscle, prevents denervation-induced nuclear accumulation of intracellular domain of the Notch receptor, and elevates expression of Numb. Numb acts as an inhibitor of Notch signaling and promotes myogenic differentiation of satellite cells. Turnover of Numb is regulated by mdm2, an E3 ubiquitin ligase.

Androgen deprivation therapy as primary treatment for prostate cancer.

Context: Hormonal therapy has been the mainstay of treatment for advanced prostate cancer for over 70 yr. The timing and extent of androgen ablative therapy for earlier stage disease remains controversial. In addition, recent studies demonstrate that so-called "castration-resistant" tumors are still dependent on androgen receptor signaling.

Prostatic acid phosphatase is expressed in human prostate cancer bone metastases and promotes osteoblast differentiation.

Prostate cancer (PCa) bone metastases are a major cause of morbidity and mortality. There are no effective therapies for PCa bone metastases that prolong survival. Prostatic acid phosphatase (PAP) is a secretory protein expressed by PCa cells.

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia.

Overview of prostate anatomy, histology, and pathology.

The human prostate is heterogeneous with regard to its embryologic origin. The two most prevalent diseases of aging males, benign prostatic hyperplasia and prostate cancer (PCa), arise from different zones within the prostate. The biology of PCa is also heterogeneous and even within a single individual there often exist prostate cancers with varying potential to progress and metastasize.

Prostaglandin E2 modulates components of the Wnt signaling system in bone and prostate cancer cells.

Both Wnt signaling and prostaglandin E(2) (PGE(2)) play pivotal roles in bone development, remodeling, osteoporosis and prostate cancer (PCa) bone metastases. We investigated the effects of PGE(2) on Wnt signaling in osteoblast-lineage cells and Wnt-inhibitor expression in PCa cells. We demonstrate that low dose PGE(2) (0.

Ribosome-inactivating proteins isolated from dietary bitter melon induce apoptosis and inhibit histone deacetylase-1 selectively in premalignant and malignant prostate cancer cells.

Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes.

Urinary bladder adenocarcinoma arising in a spina bifida patient.

Urinary bladder adenocarcinomas are rare malignancies accounting for approximately 2.5% of all urothelial neoplasms. Intestinal metaplasia of the urothelium indicates the presence of intestinal-type goblet cells and was generally observed to coexist with or to precede the diagnosis of bladder adenocarcinomas.

Concomitant secretion of glucocorticoid, androgens, and mineralocorticoid by an adrenocortical carcinoma: case report and review of literature.

Objective: To present a case of concomitant secretion of cortisol, androgens, and 11-deoxycorticosterone (DOC) by an adrenocortical carcinoma and review the literature in an attempt to identify similar cases.

Methods: The patient's medical history, physical examination, laboratory data, computed tomographic scan, and histopathologic results were analyzed and summarized in a case report, and an extensive review of the literature was performed.

Results: Endocrinologic data showed excess cortisol production, substantially elevated testosterone and androstenedione levels, and profoundly increased DOC in the setting of suppressed aldosterone.

Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway.

Although androgens stimulate bone formation the precise events underlying these effects have not been elucidated. Wnt signaling plays a central role in osteoblast development and bone formation. We demonstrated that dihydrotestosterone (DHT) significantly stimulates MC3T3 preosteoblast differentiation with no effect on cell growth.