Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies.

Resistance to anticancer therapies includes primary resistance, usually related to lack of target dependency or presence of additional targets, and secondary resistance, mostly driven by adaptation of the cancer cell to the selection pressure of treatment. Resistance to targeted therapy is frequently acquired, driven by on-target, bypass alterations, or cellular plasticity. Resistance to immunotherapy is often primary, orchestrated by sophisticated tumor-host-microenvironment interactions, but could also occur after initial efficacy, mostly when only partial responses are obtained.

Synthesis of new cyclotriphosphazene derivatives bearing Schiff bases and their thermal and absorbance properties.

In this study, a series of cyclotriphosphazene derivatives containing a Schiff base (3a-3d) were synthesized by the reactions of hexachlorocyclotriphosphazene (1) with bis-aryl Schiff bases ( - ) having different terminal groups (H, F, Cl, and Br). The products ( - ) were characterized by elemental and mass analyses, FT-IR, and H, C, and P NMR spectroscopies. Furthermore, the structure of compound was also determined by X-ray crystallography.

Characteristics and Outcome of -Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry.

AKT inhibitors have promising activity in -mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched -mutant ( = 153) and -wild-type ( = 302) metastatic breast cancer. -mutant cases had similar adjusted overall survival (OS) compared with -wild-type controls (median OS, 24.

An Accessible and Unique Insight into Metastasis Mutational Content Through Whole-exome Sequencing of Circulating Tumor Cells in Metastatic Prostate Cancer.

Background: Genomic analysis of circulating tumor cells (CTCs) could provide a unique and accessible representation of tumor diversity but remains hindered by technical challenges associated with CTC rarity and heterogeneity.

Objective: To evaluate CTCs as surrogate samples for genomic analyses in metastatic castration-resistant prostate cancer (mCRPC).

Design, Setting, And Participants: Three isolation strategies (filter laser-capture microdissection, self-seeding microwell chips, and fluorescence-activated cell sorting) were developed to capture CTCs with various epithelial and mesenchymal phenotypes and isolate them at the single-cell level.

Author Correction: Genomic characterization of metastatic breast cancers.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genomic characterization of metastatic breast cancers.

Metastasis is the main cause of death for patients with breast cancer. Many studies have characterized the genomic landscape of breast cancer during its early stages. However, there is evidence that genomic alterations are acquired during the evolution of cancers from their early to late stages, and that the genomic landscape of early cancers is not representative of that of lethal cancers.

Regiochemical Control in the Substitution Reactions of Cyclotriphosphazene Derivatives with Secondary Amines.

The substitution reactions of the monospiro and geminally disubstituted cyclotriphosphazene derivatives NPClR (R = OCH(CF)CHO (1a), SPh (1b), OCHCHCHO (1c), NHPh (1d), OCHCHCHNH (1e), NHBu (1f)) with two secondary amines (pyrrolidine and dimethylamine) were carried out to investigate geminal or non-geminal directing effects in mixed substituent cyclophosphazenes. The relative amounts of isomeric products, geminal and non-geminal trans or cis, was established quantitatively from the P NMR spectra of the reaction mixtures. Although secondary amines generally follow a non-geminal pathway in the reactions with hexachlorocyclotriphosphazene, in this work, the reactions of two different secondary amines with some NPClR (R = OCHCHCHNH, NHPh, NHBu) derivatives lead to the formation of geminal products.

Cataract Surgery and Possible Complications in Patients with Pseudoexfoliation Syndrome.

Objective: The aim of this study was to evaluate the demographic characteristics and intraoperative complications of cataract surgery in patients with pseudoexfoliation syndrome (PEX).

Materials And Methods: Cases of 225 eyes (80 eyes with pseudoexfoliation and 145 eyes without pseudoexfoliation as the control group) that underwent phacoemulsification cataract surgery and IOL implantation at the Silifke State Hospital Ophthalmology Clinic between April 2011 and April 2013 were analysed retrospectively. Patients with a history of previous ocular surgeries, ocular trauma, uveitis, glaucoma or corneal pathology were not included in the study.

Distinguishing synchronous from metachronous manifestation of distant metastases: a prognostic feature in differentiated thyroid carcinoma.

Aim: Distant metastasis has a negative impact on survival in differentiated thyroid carcinoma (DTC). The timing of this manifestation, however, is of unknown prognostic relevance. The aim of this retrospective study was to investigate the potential significance of discriminating synchronous versus metachronous distant metastases (SDM vs.

Unexpected Ring Expansion of a Four-Membered Cyclophosphazane.

Nucleophilic substitution reactions of the N(R),N(R)-spiro-bridged octachlorobis(cyclotriphosphazene), N3P3Cl4[N(CH2)5CH3]2N3P3Cl4 (1), with sodium salts of alcohols (1,3-propanediol, 2,2,3,3,4,4-hexafluoro-1,5-pentanediol, and phenol) give ansa products (2-4) via an unexpected rearrangement. These products were characterized by elemental analysis, mass spectrometry, and (1)H and (31)P NMR spectroscopy. The molecular structures of compounds 3 and 4 were also established by X-ray crystallography.

Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration.

Aim: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA), and nitric oxide (NO), as well as activity of endothelial NO synthase (eNOS), in patients with age-related macular degeneration (AMD).

Methods: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30) were compared to a control group with no retinal pathology (n=30).

Results: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.

Issues in clinical research for metastatic breast cancer.

Purpose Of Review: Technical advances and progresses in tumor biology hold promise for the advent of new anticancer agents. These changes are impacting the conduct and design of clinical trials. This review describes the changing landscape of clinical research in metastatic breast cancer (MBC).

Landscape and evolution of therapeutic research for breast cancer patients.

Breast cancer survival rates have improved, new disease classifications have been adopted, and increased awareness about symptom management has arisen. Nevertheless, it is unknown to what extent these changes have had any impact on the way clinical trials are conducted. To address this question, the evolution of clinical trials in the breast cancer field between 2007 and 2011 was evaluated.

Pneumolysin-induced CXCL8 production by nasopharyngeal epithelial cells is dependent on calcium flux and MAPK activation via Toll-like receptor 4.

The natural niche of Streptococcus pneumoniae is the nasopharyngeal mucosa and nasopharyngeal carriage of pneumococci is widely prevalent. Pneumolysin (Ply), a pore-forming protein produced by S. pneumonia, may be important in driving the innate immune response of the nasopharynx.

Primary peritoneal spindle cell sarcoma presented with massive ascites: a case report.

Soft tissue sarcomas (STSs) are a heterogeneous group of rare neoplasms originating from the embryonic mesoderm and mesenchymal cells. Primary peritoneal sarcomas have been reported as leiomyosarcoma, liposarcoma and carcinosarcoma. However, primary peritoneal spindle cell sarcoma has never been reported in the literature.

Appendicular mass imitating a malignant cecal tumor on f18-FDG PET/CT study: a case report.

Fluoro-Deoxy-Glucose Positron Emission Tomography/Computerized Tomography scan is a very useful method in the diagnosis and follow-up of gastrointestinal malignancies, although it may cause confusion in differential diagnosis.We present a 48-year-old man admitted with a right lower quadrant mass. Upon an unyielding colonoscopy due to inability to pass beyond the hepatic flexure, a Fluoro-Deoxy-Glucose Positron Emission Tomography/Computerized Tomography strongly suggested a right colonic or cecal malignancy.

Induction of CC and CXC chemokines in human antigen-presenting dendritic cells by the pneumococcal proteins pneumolysin and CbpA, and the role played by toll-like receptor 4, NF-kappaB, and mitogen-activated protein kinases.

Background: Choline-binding protein A (CbpA) and pneumolysin (Ply) can induce the expression and release of chemokines by human cells, which might modulate specific immune responses. In dendritic cells (DCs), such effects could be important for the size and character of the immunity induced if administered as vaccines. We studied the induction of CCL and CXCL chemokines by CbpA and Ply in DCs and related signaling pathways.

Comparison of ultrasound-, palpation-, and scintigraphy-guided steroid injections in the treatment of plantar fasciitis.

Background: The aim of the study was to compare the efficacies of steroid injections guided by scintigraphy, ultrasonography, and palpation in plantar fasciitis.

Methods: A total of 35 heels of 27 patients were randomly assigned to three steroid injection groups: palpation-guided (pg), ultrasound-guided (ug), and scintigraphy-guided (sg). Patients were evaluated for pain intensity before the injections and at the last follow-up of 25.

Sensitivity of iodine deficiency indicators and iodine status in Turkey.

Background: Iodine deficiency is a major health problem worldwide. Goiter prevalence and the median urinary iodine concentration in a population usually define endemic iodine deficiency. In addition to goiter prevalence and median urinary concentration, thyroid stimulating hormone (TSH) and thyroxine have been used as iodine deficiency indicators.

Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET.

Objective: Dopaminergic abnormalities in frontal-subcortical circuits have been hypothesized as the underlying pathophysiologic mechanism in Tourette's syndrome. The objective of this study was to test the hypothesis that presynaptic dopamine release from the striatum is abnormal in adults with Tourette's syndrome.

Method: Seven adults with Tourette's syndrome and five age-matched comparison subjects each received two positron emission tomography (PET) scans with high specific activity [11C]raclopride.

Positron emission tomography in the detection and management of sarcomatous transformation in neurofibromatosis.

Benign neurofibromas undergo sarcomatous transformation in approximately 5% of patients with neurofibromatosis type I. The clinical and radiologic diagnosis of sarcomatous change remains difficult. Positron emission tomography with F-18 fluorodeoxyglucose is a method to assess increased glucose metabolism in malignant tissue such as sarcomas.