A comparative safety review of histone deacetylase inhibitors for the treatment of myeloma

Introduction: Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.

Areas covered: A literature search on ‘HDAC inhibitors’ and ‘multiple myeloma’ was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.

Expert opinion: First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.     

Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

肝内胆管癌转化治疗

肝内胆管癌（ICC）可切除率低，进展期ICC的治疗有效率不高，预后很差。转化治疗在多种晚期肿瘤中有一定的疗效，是目前晚期肿瘤治疗的研究热点。随着对ICC基因组的深入了解和新的治疗药物的开发及组合，基于系统化疗的联合治疗策略，精准靶向治疗，免疫检查点抑制剂等显示出较好的疗效，使得部分进展期ICC病人能降期转化手术，获得长期生存。     

Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines

Introduction: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD.

Areas covered: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged ≤ 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.

Expert opinion: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Emerging from their burrow: Hedgehog pathway inhibitors for cancer

Introduction: Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins and mechanisms important to cancer development or survival. The Hedgehog Pathway (HhP) is a signal transduction pathway and its constitutive activation is tumorigenic in basal cell carcinoma (BCC). The HhP enables phenotypic flexibility, and channels tumor-stroma interactions. As a result, it is over-expressed in numerous cancers as well as in the tumor microenvironment and may represent a promising therapeutic target.

Areas covered: In this article, we review the rationale for targeting HhP and its role as an oncogenic driver, in tumor epithelial-to-mesenchymal transition (EMT), and in the tumor microenvironment and describe the results of preclinical and clinical studies involving HhP inhibitors.

Expert opinion: HhP activation plays an important role in both the tumor microenvironment and tumor EMT which can lead to treatment resistance for a number of different malignancies. In addition to standard use in BCC, several HhP inhibitors are in preclinical, early, and mid-stage clinical development for other solid and hematologic malignancies.