Thymic adenocarcinoma presenting as an incidental mediastinal mass.

Background: Primary thymic adenocarcinoma represents an exceptionally rare malignancy, for which the cornerstone of therapy is margin-negative resection, with radiation and systemic therapy reserved for invasive and advanced disease. Thymic adenocarcinoma has not been previously reported in the setting of a concomitant malignancy, as reported herein.

Case Presentation: We present a case of a 55-year-old previously healthy male diagnosed with acute myeloid leukemia, also found to have a mediastinal mass.

Meeting the New Commission on Cancer Operative Standards: Where Do We Stand Now?

Introduction: The 2020 Commission on Cancer accreditation standards 5.7 and 5.8 address total mesorectal excision for rectal cancer and lymph node sampling for lung cancer.

The use of lobectomy for management of clinically significant pulmonary vein stenosis and occlusion refractory to percutaneous intervention.

Pulmonary vein stenosis (PVS) is a serious complication of radiofrequency ablation (RFA) for the treatment of atrial fibrillation. The prevalence of this complication was reported to be as high as 42% in 1999 when RFA was first implemented [1]. However, with improvements in operator technique including wide area circumferential ablation, antral isolation, and the use of intracardiac ultrasound, the incidence of symptomatic severe PVS following RFA ranges from 0% to 2.

Necrotizing soft tissue infection following a peripheral bypass.

Background: Necrotizing soft tissue infection (NSTI), formerly referred to as necrotizing fasciitis, is a rare but serious postoperative complication. NSTI following arterial bypass is seen only once in the literature (for a coronary artery bypass) and is not mentioned following peripheral bypass. Although surgical site infections have been studied extensively, there are limited published data on postoperative NSTI and no data for NSTI following peripheral arterial bypass.

Spinal epidural abscess due to tropical pyomyositis in immunocompetent adolescents.

Pyomyositis, a suppurative infection of skeletal muscle, is a disease not frequently encountered by neurosurgical providers. While previously considered an infection localized to tropical and semitropical locations, clinical reports of pyomyositis in temperate climates have increased over the past decade. Paraspinal involvement is uncommon in pyomyositis; however, the potential exists for spread into the epidural space resulting in a spinal epidural abscess (SEA).

Sequence-dependent administration of 5-fluorouracil maintains methotrexate antineoplastic activity in human estrogen-negative breast cancer and protects against methotrexate cytotoxicity in human bone marrow.

Background: Breast cancer is a leading cause of morbidity and mortality in women in developed countries and in increasingly developing countries. In general, estrogen receptor (ER)-positive breast cancers have a better prognosis and are often more responsive to anti-estrogen therapy. Unfortunately, ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens.

Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.

Background: Breast cancer patients are at increased risk of osteoporosis. Contributing factors include age and/or chemotherapy. The selective estrogen modulator, raloxifene (RAL), effective in the prevention of breast cancer and approved for the treatment and prevention of osteoporosis, may prove beneficial in current breast cancer treatment modules.

Ligand binding and circular permutation modify residue interaction network in DHFR.

Residue interaction networks and loop motions are important for catalysis in dihydrofolate reductase (DHFR). Here, we investigate the effects of ligand binding and chain connectivity on network communication in DHFR. We carry out systematic network analysis and molecular dynamics simulations of the native DHFR and 19 of its circularly permuted variants by breaking the chain connections in ten folding element regions and in nine nonfolding element regions as observed by experiment.

Sequence-dependent administration of raloxifene and 5-fluorouracil/pemetrexed protects against pemetrexed cytotoxicity in human bone marrow.

Background: Pemetrexed (Alimta) is a new-generation multitargeted antifolate that inhibits several key enzymes in the de novo pathways of pyrimidine and purine biosynthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). Alimta has demonstrated antitumor activity in a broad array of human malignancies, e.g.

The protection against trimetrexate cytotoxicity in human bone marrow by sequence-dependent administration of raloxifene, 5-fluorouracil/trimetrexate.

Background: Currently, one of the most effective strategies for the treatment and prevention of breast cancer is the use of drugs that block estrogen action in the breast. The success of the first clinically relevant selective estrogen receptor modulator (SERM), tamoxifen, provided the foundation for further testing of this drug to reduce breast cancer incidence in high-risk women. However, the negative effects associated with the long-term use of tanrhoxifen have initiated the search for compounds that are more effective but less toxic.

Raloxifene attenuation of methotrexate cytotoxicity in human bone marrow by sequence-dependent administration of raloxifene, 5-FU/methotrexate.

Background: Increasing evidence suggests that adjuvant systemic chemotherapy is necessary for the survival of breast cancer patients. Antitumor agents are more effective when used in combination with drugs exhibiting different mechanisms of action than when used alone. Previous studies from this laboratory have shown that raloxifene (RAL) attenuation of 5-fluorouracil/methotrexate (5-FU/MTX) cytotoxicity to breast cancer cells was sequence-dependent.

Raloxifene attenuation of 5-FU/methotrexate cytotoxicity in human breast cancer cells: the importance of sequence in combination chemotherapy.

Background: The selective estrogen receptor modulator raloxifene (RAL), used to treat and prevent osteoporosis, is under investigation for its use in the treatment and prevention of breast cancer. RAL in combination with the antimetabolites methotrexate (MTX) and 5-fluorouracil (5-FU) has not been extensively studied. Because RAL and the antimetabolites target different phases of the cell cycle and exhibit different mechanisms of action and clinical toxicity, the effects of sequence of administration on the growth inhibition of MCF-7 human breast cancer cells were investigated.

Barnase thermal titration via molecular dynamics simulations: detection of early denaturation sites.

The thermal stability of barnase has been studied using constant pressure and temperature (CPT) molecular dynamics at different temperatures. Barnase X-ray coordinates were obtained from the Research Collaboratory for Structural Bioinformatics (RCSB) Protein Data Bank (PDB code:1rnb). Simulations were performed at 285, 295, 300, 335, 345, and 395 K in explicit water under periodic boundary conditions for 280 ps.

Sequence- and time-dependent antagonism between raloxifene and methotrexate in human breast cancer cells.

The selective estrogen receptor modulator (SERM) and an agent for the prevention of osteoporosis in postmenopausal women, raloxifene (Ral), decreased high-dose methotrexate (MTX) cytotoxicity in MCF-7 breast cancer cells. When Ral is given at least 24 hours prior to MTX, the resultant interaction is antagonistic. However, when breast cancer cells are exposed to Ral 24 hours after MTX, the interaction between Ral and MTX is not antagonistic.