Autophagy and urothelial carcinoma of the bladder: A review.

The incidence of urothelial carcinoma of the urinary bladder (bladder cancer) remains high. While other solid organ malignancies have seen significant improvement in morbidity and mortality, there has been little change in bladder cancer mortality in the past few decades. The mortality is mainly driven by muscle invasive bladder cancer, but the cancer burden remains high even in nonmuscle invasive bladder cancer due to high recurrence rates and risk of progression. While apoptosis deregulation has long been an established pathway for cancer progression, nonapoptotic pathways have gained prominence of late. Recent research in the role of autophagy in other malignancies, including its role in treatment resistance, has led to greater interest in the role of autophagy in bladder cancer. Herein, we summarize the literature regarding the role of autophagy in bladder cancer progression and treatment resistance. We address it by systematically reviewing treatment modalities for nonmuscle invasive and muscle invasive bladder cancer

Outcomes and quality of life issues in the pharmacological management of benign prostatic hyperplasia (BPH)

BackgroundBenign prostatic hyperplasia (BPH) is a common disease of the aging male population. BPH treatment includes a variety of pharmacological and surgical interventions. The goal of this paper is to review the natural history of BPH, outcomes of pharmacological management, effects on quality of life (QoL), future pharmacotherapies, and associated patient-focused perspectives.Materials and methodsMedline searches for the keywords benign prostatic hyperplasia, BPH, alpha blockers, 5 alpha-reductase, and quality of life were performed. Relevant literature was reviewed and analyzed.ResultsAlpha blockers, 5 alpha-reductase inhibitors, and phytotherapy are the three categories of pharmaceutical interventions currently available for BPH. Various clinical trials have shown that alpha blockers and 5 alpha-reductase inhibitors are safe, efficacious, and improve QoL in patients with BPH. The evidence for phytotherapeutics is not as convincing. The current armamentarium of pharmaceutical interventions are encompassed in these three classes of medications. New pharmacotherapies based on novel mechanisms are on the horizon.ConclusionThere are a variety of safe and efficacious medical therapies available for the management of BPH and it is important for the practicing physician to have an understanding of these pharmacotherapies and their potential impact on the patient. There is not enough evidence to make a recommendation regarding phytotherapy use. New classes of drugs for BPH will likely find their way into routine use

Retroperitoneal extramedullary hematopoietic pseudotumor in ataxia-telangiectasia.

Ataxia-telangiectasia confers a significant increase in the development of several cancer types, most commonly leukemia and lymphoma. However, as the natural history for these patients is evolving and their lifespan is increasing, there is the potential for the development of additional uncommon tumors in an already rare patient population. We report the first case, to our knowledge, of an incidental retroperitoneal tumor in a 26-year-old woman undergoing evaluation for hepatic dysfunction. The mass was suspicious for retroperitoneal sarcoma, but proved to be an extramedullary hematopoietic pseudotumor after extensive pathologic evaluation. The changing landscape of neoplasms associated with ataxia-telangiectasia is discussed with emphasis on previously underreported benign and malignant tumors

Epigenomic Regulation of Androgen Receptor Signaling: Potential Role in Prostate Cancer Therapy.

Androgen receptor (AR) signaling remains the major oncogenic pathway in prostate cancer (PCa). Androgen-deprivation therapy (ADT) is the principle treatment for locally advanced and metastatic disease. However, a significant number of patients acquire treatment resistance leading to castration resistant prostate cancer (CRPC). Epigenetics, the study of heritable and reversible changes in gene expression without alterations in DNA sequences, is a crucial regulatory step in AR signaling. We and others, recently described the technological advance Chem-seq, a method to identify the interaction between a drug and the genome. This has permitted better understanding of the underlying regulatory mechanisms of AR during carcinogenesis and revealed the importance of epigenetic modifiers. In screening for new epigenomic modifiying drugs, we identified SD-70, and found that this demethylase inhibitor is effective in CRPC cells in combination with current therapies. The aim of this review is to explore the role of epigenetic modifications as biomarkers for detection, prognosis, and risk evaluation of PCa. Furthermore, we also provide an update of the recent findings on the epigenetic key processes (DNA methylation, chromatin modifications and alterations in noncoding RNA profiles) involved in AR expression and their possible role as therapeutic targets

Questioning the status of the treaty on the prohibition of nuclear weapons as a ‘humanitarian disarmament’ agreement

On 22 January 2021, the Treaty on the Prohibition of Nuclear Weapons (TPNW) entered into force. The TPNW has resulted in a mixed response from the international community, instigating much discussion on certain provisions and features of the TPNW. Yet underpinning these analyses rests a commonly shared premise; that the TPNW constitutes a further example of humanitarian disarmament, placing the interests of victims and humanity at the centre of discussions of nuclear weapons and disarmament. This article seeks to reveal a coinciding yet somewhat underexplored, hidden nature of the TPNW by demonstrating how the treaty also incorporates State-based security-driven interests alongside these humanitarian aspirations. While most commentators do not deny the existence of such interests at stake in the TPNW process, few have analysed the extent to which State-based security considerations have been incorporated in the final text of the TPNW. After having revealed the continued presence of State-centred security considerations in the TPNW’s negotiation, preambular provisions and operative text, this article concludes by discussing some possible implications stemming from the determination that the TPNW is inspired by, and reflects, both humanitarian and security objectives

Going, going, gone? Assessing Iran’s possible grounds for withdrawal from the treaty on the non-proliferation of nuclear weapons

The recent targeted attack resulting in the death of Qassem Soleimani has received extensive attention for its violations of international law by the United States. However, one area that has not been considered following the 3 January 2020 attack is the possible consequences this may have for Iran’s nuclear non-proliferation legal obligations. Iranian officials have previously alluded to the possibility of Iran withdrawing from the NPT following the US withdrawal from the Joint Comprehensive Plan of Action in May 2018 and re-imposition of targeted economic sanctions against Iran. This article considers whether Iran can withdraw from the Treaty on the Non-Proliferation of nuclear Weapons (NPT) 1968, thus freeing Iran from its legal commitments not to develop nuclear weapons. It revisits the withdrawal provisions found in Article X of the NPT and examines the invocation of the ‘extraordinary events’ clause by other states in relation to other instruments too. In light of this, the discussion considers whether Iran can legally withdraw from the NPT, before concluding with some thoughts as to whether it should in fact pursue this option

Remedying the limitations of the CTBT? Testing under the treaty on the prohibition of nuclear weapons

Various limitations on the testing of nuclear weapons already exist within international law, including the Partial Test-Ban Treaty of 1963, along with further restrictions on where testing is permitted, and the maximum yield of such tests. Yet it was not until 1996 that the Comprehensive Test-Ban Treaty (CTBT) was adopted, the first attempt to prohibit all forms of testing that result in a nuclear weapon ‘explosion’. The CTBT does not, however, cover computer simulated and sub-critical nuclear tests, which can ensure the safety and reliability of existing stockpiles, thus undermining the CTBT’s implications for nuclear disarmament. More importantly, due to the onerous entry-into-force requirements under Article XIV, the CTBT is not yet binding on states, and is unlikely to become so in the near future. A further contribution to the legal restrictions on nuclear weapon testing has recently been provided by the Treaty on the Prohibition of Nuclear Weapons (TPNW), which was adopted in July 2017. Under Article 1(1)(a), state parties undertake never under any circumstances, to ‘develop’ or ‘test’ nuclear weapons or other nuclear explosive devices’. Given the challenges facing the CTBT, this Article seeks to analyse the extent of the testing prohibition established under Article 1(1)(a), as well as the scope of the prohibition of development in order to determine whether the TPNW closes the testing ‘loophole’ established by the CTBT by including sub-critical and computer simulated testing within either of these undertakings. The article will conclude by offering some thoughts on the TPNW’s prospects for entry-into-force and its future relationship with the CTBT

Two-dimensional colloidal fluids exhibiting pattern formation

Fluids with competing short range attraction and long range repulsive interactions between the particles can exhibit a variety of microphase separated structures. We develop a lattice-gas (generalised Ising) model and analyse the phase diagram using Monte Carlo computer simulations and also with density functional theory (DFT). The DFT predictions for the structures formed are in good agreement with the results from the simulations, which occur in the portion of the phase diagram where the theory predicts the uniform fluid to be linearly unstable. However, the mean-field DFT does not correctly describe the transitions between the different morphologies, which the simulations show to be analogous to micelle formation. We determine how the heat capacity varies as the model parameters are changed. There are peaks in the heat capacity at state points where the morphology changes occur. We also map the lattice model onto a continuum DFT that facilitates a simplification of the stability analysis of the uniform fluid.Comment: 13 pages, 15 figure

Dispersion and separation of nanostructured carbon in organic solvents

The present invention relates to dispersions of nanostructured carbon in organic solvents containing alkyl amide compounds and/or diamide compounds. The invention also relates to methods of dispersing nanostructured carbon in organic solvents and methods of mobilizing nanostructured carbon. Also disclosed are methods of determining the purity of nanostructured carbon