ABSTRACT
Paraneoplastic pemphigus (PNP) is a rare syndrome driven by antibodies (IgG) binding to desmogleins and other epidermal proteins leading to skin erosions. In rare instances, these same IgG proteins may also target the bronchial mucosa leading to an irreversible fibrotic reaction within the epithelium and subsequent obstructive lung disease. A 51-year-old man presented to the emergency department with 2-3-month history of dyspnoea as well as oral and genital ulcerations and inguinal lymphadenopathy. The ulcerations were biopsied and proven to be consistent with pemphigus. Subsequent inguinal lymph node biopsy implicated the hyaline-vascular variant of Castleman's disease (CD), as the primary cause of the patient's pemphigus. The patient underwent pulmonary function testing that demonstrated severe airflow obstruction. The patient was diagnosed with PNP and associated bronchiolitis obliterans syndrome (BOS). He was treated with rituximab for his CD, and oral and inhaled corticosteroids along with azithromycin for his BOS.
Subject(s)
Castleman Disease/diagnosis , Dyspnea/etiology , Paraneoplastic Syndromes/diagnosis , Pemphigus/diagnosis , Ulcer/etiology , Bronchiolitis Obliterans/diagnosis , Bronchiolitis Obliterans/drug therapy , Castleman Disease/drug therapy , Diagnosis, Differential , Humans , Male , Middle Aged , Mouth Diseases/etiology , Paraneoplastic Syndromes/drug therapy , Pemphigus/drug therapy , Penile Diseases/etiology , Treatment OutcomeABSTRACT
The discovery that noncoding components of the genome, including microRNA (miRNA or miR), can contribute to the pathogenesis of cancer has led investigators to contemplate using these molecules to guide clinical decision making. Currently, miRNA signatures are being applied in human clinical trials and miRNA-directed therapy is under way, with miR-122 targeting in hepatitis C (HCV) being the most developed therapy thus far. miRNA-based targeting in cancer is not far behind, with several private companies developing therapeutics. We are recognizing the potential for miRNA biology to clarify both the molecular pathogenesis of cancer and the inherent complexities in translating its biology to clinics. An increased understanding of fundamental miRNA biology, improved bioinformatics, and directed in vivo targeting while minimizing off-target effects and toxicity will be required for successful translational application. Here, we provide an overview of miRNAs, with a focus on aspects of translating bench-based discoveries to the clinic.
Subject(s)
Gene Targeting/methods , MicroRNAs/genetics , Neoplasms/genetics , Neoplasms/therapy , Animals , Clinical Trials as Topic/methods , Clinical Trials as Topic/trends , Drug Discovery/methods , Gene Targeting/trends , Humans , MicroRNAs/administration & dosage , MicroRNAs/adverse effects , Neoplasms/etiologyABSTRACT
Crk is a member of a family of adaptor proteins that are involved in intracellular signal pathways altering cell adhesion, proliferation, and migration. Increased expression of Crk has been described in lung cancer and associated with increased tumor invasiveness. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-25 nt long) that are capable of targeting genes for either degradation of mRNA or inhibition of translation. Crk is a predicted putative target gene for miR-126. Over-expression of miR126 in a lung cancer cell line resulted in a decrease in Crk protein without any alteration in the associated mRNA. These lung cancer cells exhibit a decrease in adhesion, migration, and invasion. Decreased cancer cell invasion was also evident following targeted knockdown of Crk. MiR-126 alters lung cancer cell phenotype by inhibiting adhesion, migration, and invasion and the effects on invasion may be partially mediated through Crk regulation.
