Analysis of pulmonary complications and predicted postoperative pulmonary function in oncologic lung resections.

Background: Postoperative pulmonary complications (PPCs) represent a significant source of morbidity and mortality in surgical patients. Measurement of predicted postoperative forced expiratory volume in the first second (ppo FEV1) may allow for reliable prediction of PPCs and perioperative planning. This study aimed to determine if impaired ppo FEV1 is associated with increased risk of PPCs following oncologic lung resection.

IRIS: Discovery of cancer immunotherapy targets arising from pre-mRNA alternative splicing.

Alternative splicing (AS) is prevalent in cancer, generating an extensive but largely unexplored repertoire of novel immunotherapy targets. We describe soform peptides from NA splicing for mmunotherapy target creening (IRIS), a computational platform capable of discovering AS-derived tumor antigens (TAs) for T cell receptor (TCR) and chimeric antigen receptor T cell (CAR-T) therapies. IRIS leverages large-scale tumor and normal transcriptome data and incorporates multiple screening approaches to discover AS-derived TAs with tumor-associated or tumor-specific expression.

Pilot study on the bioactivity of vitamin d in the skin after oral supplementation.

Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR).

Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists.

Recognition of the multiple roles of Hedgehog signaling in cancer has prompted intensive efforts to develop targeted pathway inhibitors. Leading inhibitors in clinical development act by binding to a common site within Smoothened, a critical pathway component. Acquired Smoothened mutations, including SMO(D477G), confer resistance to these inhibitors.

Structure and replication of yDNA: a novel genetic set widened by benzo-homologation.

In a functioning genetic system, the information-encoding molecule must form a regular self-complementary complex (for example, the base-paired double helix of DNA) and it must be able to encode information and pass it on to new generations. Here we study a benzo-widened DNA-like molecule (yDNA) as a candidate for an alternative genetic set, and we explicitly test these two structural and functional requirements. The solution structure of a 10 bp yDNA duplex is measured by using 2D-NMR methods for a simple sequence composed of T-yA/yA-T pairs.

Polymerase amplification, cloning, and gene expression of benzo-homologous "yDNA" base pairs.

A widened DNA base-pair architecture is studied in an effort to explore the possibility of whether new genetic system designs might possess some of the functions of natural DNA. In the "yDNA" system, pairs are homologated by addition of a benzene ring, which yields (in the present study) benzopyrimidines that are correctly paired with purines. Here we report initial tests of ability of the benzopyrimidines yT and yC to store and transfer biochemical and biological information in vitro and in bacterial cells.

Synthesis and properties of size-expanded DNAs: toward designed, functional genetic systems.

We describe the design, synthesis, and properties of DNA-like molecules in which the base pairs are expanded by benzo homologation. The resulting size-expanded genetic helices are called xDNA ("expanded DNA") and yDNA ("wide DNA"). The large component bases are fluorescent, and they display high stacking affinity.

Exploring the limits of DNA size: naphtho-homologated DNA bases and pairs.

A new design for DNA bases and base pairs is described in which the pyrimidine bases are widened by naphtho-homologation. Two naphtho-homologated deoxyribosides, dyyT (1) and dyyC (2), were synthesized and could be incorporated into oligonucleotides as suitably protected phosphoramidite derivatives. The deoxyribosides were found to be fluorescent, with emission maxima at 446 and 433 nm, respectively.

A new four-base genetic helix, yDNA, composed of widened benzopyrimidine-purine pairs.

We describe the properties of stable DNA-like self-assembled helices composed entirely of base pairs involving two new size-expanded pyrimidines. We term this new helix geometry "yDNA" (an abbreviation of "wide DNA"). The new pyrimidine analogues, yT and yC, are increased in size by benzo-homologation and have a geometry that is distinct from previous size-expanded pyrimidines.

Novel benzopyrimidines as widened analogues of DNA bases.

We report on the synthesis, stacking, and pairing properties of a new structural class of size-expanded pyrimidine nucleosides, abbreviated dyT and dyC. Their bases are benzo-homologated variants of thymine and cytosine and have a design that is distinct from a previously described class of size-expanded (xDNA) pyrimidines, with a different vector of expansion relative to the sugar. We term this new base geometry "yDNA" (a mnemonic for "wide DNA").

G-quadruplex as a new class of structural entities for directing the formation of circular oligodeoxyribonucleotides.

It has been demonstrated for the first time that G-quadruplex is capable of acting as a template for directing the sequence-specific formation of certain circular oligodeoxyribonucleotides with high efficiency.

Acid-promoted DNA-cleaving activities and total synthesis of varacin C.

The first total synthesis of the antibiotic varacin C has been accomplished. In addition, it has been demonstrated that this antibiotic exhibits potent antitumor activity and is capable of causing efficient DNA cleavage under acidic conditions.

Benzotrithiole 2-oxide: a new family of thiol-activated DNA-cleaving functionalities.

It was demonstrated in our studies that benzotrithiole 2-oxide was capable of causing efficient DNA cleavage in the presence of 2-mercaptoethanol or glutathione and exhibited potent cytotoxic properties against certain cancer cell lines.

Acid-accelerated DNA-cleaving activities of antitumor antibiotic varacin.

It is demonstrated in this report that the authentic molecular structure of antibiotic varacin is capable of causing DNA-cleavage with high efficiency in the presence of thiols. In addition, it is found that the DNA-cleaving activity by varacin is apparently promoted by its acidic environments.