A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy-induced tumorigenesis and drug resistance including Beclin-1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF-2, MEG3, LAPTM4B, mTOR, BRAF and c-MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.
Antineoplastic Agents/pharmacology , Autophagy , Biomarkers, Tumor/metabolism , Carcinogenesis/drug effects , Drug Resistance, Neoplasm , Neoplasms/drug therapy , Neoplasms/pathology , Carcinogenesis/metabolism , Carcinogenesis/pathology , Humans , Neoplasms/metabolism
Chronic lymphocytic leukemia (CLL) typically affects older patients; administration of traditional cytotoxic therapies in old patients has very modest benefit with no survival improvement. With better understanding of CLL biology, trends are shifting towards the use of targeted therapies. The objective of this article is to review the safety and efficacy of various novel agents that specifically target the dysregulated pathways, with particular attention to elderly patients. Agents like B-cell receptor (BCR) inhibitors (Bruton's tyrosine kinase inhibitors [ibrutinib]), phosphatidylinositol 3-kinase inhibitors (idelalisib), spleen tyrosine kinase inhibitors (entospletinib), Bcl-2 inhibitors (venetoclax), immunomodulators (lenalidomide), and monoclonal antibodies (obinutuzumab, ofatumumab) have shown activity in CLL with a very favorable toxicity profile. Newer agents have improved clinical outcomes, and have tolerable toxicity profiles in elderly patients, resulting in the treatment with individualized therapy approach for CLL.
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Aged , Humans
Alzheimer's disease (AD) is the most common cause of dementia in elderly patients, affecting individuals older than 60 years. It is a complex degenerative brain disease characterized by progressive cognitive impairment. AD constitutes a major global health concern. A central role for inflammation has been implicated in the pathogenesis of AD. Despite the understanding of multiple molecular pathways in the pathophysiology of AD, novel treatment agents with a possible role in modifying the disease activity are still lacking. Our article provides a comprehensive review of various observational studies and randomized trials encompassing the use of anti-inflammatory agents in the management of AD patients and utilizes the conclusions derived therefrom to give recommendations in this regard.
We report a case of peripartum cardiomyopathy (PPCM), which presented with antenatal pre-eclampsia complicated by acute kidney injury (AKI). A 25-year-old patient in her 27th week of gestation presented with high blood pressure. She was later diagnosed with PPCM, which was complicated by AKI. Our case report indicated PPCM presentation during the prepartum period, which is a rare entity. On her fifth day of admission, our patient had spontaneous expulsion of her neonate, who was found to be dead on antenatal ultrasound.
