Improving cancer immunotherapy with DNA methyltransferase inhibitors.

Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity.

The biology of ependymomas and emerging novel therapies.

Ependymomas are rare central nervous system tumours that can arise in the brain's supratentorial region or posterior fossa, or in the spinal cord. In 1924, Percival Bailey published the first comprehensive study of ependymomas. Since then, and especially over the past 10 years, our understanding of ependymomas has grown exponentially. In this Review, we discuss the evolution in knowledge regarding ependymoma subgroups and the resultant clinical implications. We also discuss key oncogenic and tumour suppressor signalling pathways that regulate tumour growth, the role of epigenetic dysregulation in the biology of ependymomas, and the various biological features of ependymoma tumorigenesis, including cell immortalization, stem cell-like properties, the tumour microenvironment and metastasis. We further review the limitations of current therapies such as relapse, radiation-induced cognitive deficits and chemotherapy resistance. Finally, we highlight next-generation therapies that are actively being explored, including tyrosine kinase inhibitors, telomerase inhibitors, anti-angiogenesis agents and immunotherapy.

Post-traumatic Late Presentation of Morel-Lavallée: Case Report and Review of Literature.

INTRODUCTION: Morel-Lavallée (MLL) is an uncommon entity that is missed by many physicians, it is the result of a shearing force that leads to degloving of the subcutaneous fat from the underlying deep fascia. CASE REPORT: We present a case of a 15-year-old male patient who presented 3 months after the initial crush injury with a large MLL lesion at the lateral aspect of the right proximal thigh. He was treated with incision and drainage with compressive dressing and a negative pressure drain. CONCLUSION: Diagnosis of MLL is usually clinical and can be aided with radiological tools like MRI that is the gold standard of imaging in this lesion. Several treatment options are available, ranging from conservative treatment with compressive bandages to percutaneous drainage, injection of sclerotic agents, and surgical treatment with incision, drainage, and debridement. Diagnosis and treatment should be familiar to all caregivers to prevent further complications that could be life or organ-threatening.

Immunomodulatory Properties of Coriolus versicolor: The Role of Polysaccharopeptide.

Traditional uses of herbal medicine have depended mostly on anecdotal evidence for much of history. The increasing application of scientific rigor to the study some of these traditional therapies in recent years has revealed potent bioactivity, notably demonstrated by the 2015 Nobel Prize for the discovery of an antimalarial compound from traditional Chinese herbs. Given the recent successes of immunotherapy and checkpoint blockade, there is a renewed interest in identifying new drugs with immunomodulatory effects. As an estimated 45-60% of cancer patients worldwide are reported to use complementary alternative medicine alongside traditional therapy, this review will highlight the literature on the immunomodulatory effects of one of these compounds. We report on the induction of a largely pro-inflammatory cytokine profile by the polysaccharopeptide (PSP) isolated from the Coriolus versicolor (Yun zhi) mushroom, as well as its effects on various immune subsets, and the clinical data that have led to its widespread adoption as an adjunct cancer therapeutic in many Eastern cultures. Particular focus is given to the potential mechanisms underlying the bioactivity of PSP and reports of its ability to promote antitumor immunity by helping overcome tolerogenic tumor microenvironments.

Decitabine Enhances Lymphocyte Migration and Function and Synergizes with CTLA-4 Blockade in a Murine Ovarian Cancer Model.

The lack of second-line treatment for relapsed ovarian cancer necessitates the development of improved combination therapies. Targeted therapy and immunotherapy each confer clinical benefit, albeit limited as monotherapies. Ovarian cancer is not particularly responsive to immune checkpoint blockade, so combination with a complementary therapy may be beneficial. Recent studies have revealed that a DNA methyl transferase inhibitor, azacytidine, alters expression of immunoregulatory genes in ovarian cancer. In this study, the antitumor effects of a related DNA methyl transferase inhibitor, decitabine (DAC), were demonstrated in a syngeneic murine ovarian cancer model. Low-dose DAC treatment increases the expression of chemokines that recruit NK cells and CD8(+) T cells, promotes their production of IFNγ and TNFα, and extends the survival of mice bearing subcutaneous or orthotopic tumors. While neither DAC nor immune checkpoint blockade confers durable responses as a monotherapy in this model, the efficacy of anti-CTLA-4 was potentiated by combination with DAC. This combination promotes differentiation of naïve T cells into effector T cells and prolongs cytotoxic lymphocyte responses as well as mouse survival. These results suggest that this combination therapy may be worthy of further consideration for improved treatment of drug-resistant ovarian cancer.

Prevalence and risk factors of obesity and hypertension among students at a central university in the West Bank.

OBJECTIVES: We aimed to determine the prevalence and correlates of obesity and hypertension (HTN) among students at a central university in the West Bank. MATERIALS AND METHODS: This cross-sectional study targeted a cohort of 553 students (59.5% males, 40.5% females) aged 17-26 years (median = 21) from Al-Quds University. Body mass index (BMI) and blood pressure (BP) were measured. Participants completed a questionnaire on physical activity, sedentary behavior, dietary factors, smoking and family history of obesity, HTN, and coronary artery disease. The magnitude of correlation was assessed by Spearman's rho (r(s)) and Chi-square tests. RESULTS: The prevalence of overweight was 25% (31.1% males, 15.6% females) and obesity 7.2% (9.4% males, 4% females). Obesity and overweight were associated with family history of obesity in both genders (p<0.001) and physical activity in males (r(s)= - 0.162, p<0.005). No correlation was demonstrated between participants' BMI and sedentary lifestyle or consumption of fast food. Pre-HTN was detected in 27.1% (38% males, 11.2% females) and HTN in 2.2% (3.3% males, 0.4% females). Pre-HTN and HTN were associated with obesity (r(s)=0.252, p<0.001) and smoking (p<0.05). No relationship was detected between students' BP and sedentary behavior, family history of HTN/CAD, or consumption of fast food. The prevalence of increased BMI and BP among males was significantly higher than females (p<0.001). CONCLUSIONS: We detected a high prevalence of elevated BP and excess weight gain among students at Al-Quds University. An interventional program is urgently needed to control these cardiovascular risk factors in this community.