Metastatic Medullary Carcinoma of Thyroid Presenting as a Dural-Based Mass: Case Report and Review of Literature

Dural metastasis from medullary thyroid carcinoma (MTC) is not well established in English literature. We present the case report of MTC with unusual clinical presentation as a dural-based mass in a 39-year-old male with no family history of multiple endocrine neoplasia syndrome. Magnetic resonance imaging showed an extra-axial dural-based mass in right frontal lobe with calvarium and soft tissue extension to the right superior orbit. Histopathology showed MTC with variegated morphology and various patterns. Thyroid mass and widespread metastases from medullary thyroid carcinoma were subsequently identified.     

Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer

Cancer Chemotherapy and Pharmacology - CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize...     

Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia

Dysregulation of apoptotic machinery is one mechanism by which acute myeloid leukemia (AML) acquires a clonal survival advantage. B-cell lymphoma protein-2 (BCL2) overexpression is a common feature in hematologic malignancies. The selective BCL2 inhibitor, venetoclax (VEN) is used in combination with azacitidine (AZA), a DNAmethyltransferase inhibitor (DNMTi), to treat patients with AML. Despite promising response rates to VEN/AZA, resistance to the agent is common. One identified mechanism of resistance is the upregulation of myeloid cell leukemia-1 protein (MCL1). Pevonedistat (PEV), a novel agent that inhibits NEDD8-activating enzyme, and AZA both upregulate NOXA (PMAIP1), a BCL2 family protein that competes with effector molecules at the BH3 binding site of MCL1. We demonstrate that PEV/AZA combination induces NOXA to a greater degree than either PEV or AZA alone, which enhances VEN-mediated apoptosis. Herein, using AML cell lines and primary AML patient samples ex vivo, including in cells with genetic alterations linked to treatment resistance, we demonstrate robust activity of the PEV/VEN/AZA triplet. These findings were corroborated in preclinical systemic engrafted models of AML. Collectively, these results provide rational for combining PEV/VEN/AZA as a novel therapeutic approach in overcoming AML resistance in current therapies.     

Randomized trial of influenza vaccine with granulocyte-macrophage colony-stimulating factor or placebo in cancer patients.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) would improve response to influenza vaccination in cancer patients. PATIENTS AND METHODS: In a randomized, patient-blinded, placebo-controlled trial carried out in 1997 to 2000, 133 patients were stratified into five groups of treatment and disease. Single doses of standard split trivalent influenza vaccine and either placebo or 250 micro g of GM-CSF were administered at the same time. Hemagglutination inhibition assay titers were measured before and 4 weeks after vaccination. RESULTS: Standard analyses, which define response as at least a four-fold increase in titers, detect no effect of GM-CSF for any of the three influenza subtypes in the trivalent vaccines (P >or=.12). Analysis that includes the magnitude of the change in titers and combines responses of the subtypes suggests that the placebo group had the greater response (P =.051), thus indicating that GM-CSF does not improve response. Ancillary analyses show that response declines both with increasing age and with higher initial titers. The fraction of patients with at least a four-fold increase in titers was 0.36 (95% confidence interval, 0.29 to 0.42) CONCLUSION: A single 250- micro g dose of GM-CSF administered with the influenza vaccine does not improve response to vaccination. Response in cancer patients is low and declines as age and initial titer increase.     

Ovarian pregnancy: a case report

We report a rare case of ovarian pregnancy occurring in a 34-year old woman after natural conception. The natural history, management, and outcome of this rare extrauterine pregnancy are described.     

Comparison of a semipermeable dressing bonded to an absorbent pad and a semipermeable dressing over a separate gauze pad for containment of vaccinia virus at the vaccination site.

OBJECTIVE: To compare the ability of 2 types of dressings to contain vaccinia virus after smallpox vaccination. DESIGN: Prospective, nonrandomized trial. SETTING: The smallpox vaccination clinic in a medium-sized military hospital. PARTICIPANTS: Ninety-seven active-duty military members who received smallpox vaccination in accordance with US Department of Defense and Centers for Disease Control and Prevention guidelines. METHODS: The first 40 participants enrolled were instructed to cover their vaccination sites with a semipermeable membrane placed over a separate gauze pad, and the subsequent 57 participants were given a semipermeable membrane bonded to an absorbent pad. Swab samples of the external surface of the dressing were collected 7 and 21 days after vaccination. Real-time quantitative polymerase chain reaction was used to detect vaccinia DNA in the samples. RESULTS: The rate of vaccinia DNA detection was significantly higher for samples obtained from vaccinees who were using the separate gauze and semipermeable membrane, compared with the vacinees who were using the gauze-impregnated semipermeable membrane (22% vs 2.2%; ; odds ratio, 12.3 [95% confidence interval, 1.4-567.4]). CONCLUSION: A gauze-impregnated semipermeable membrane more effectively reduced viral passage to the external surface of the dressing than did a semipermeable membrane placed over a separate gauze pad. Routine use of such dressings following smallpox vaccination might reduce the incidence of autoinoculation and secondary transmission.