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Antibiotic exposure is associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). We analyzed antibiotic prescription patterns in lung cancer and melanoma, two malignancies in which ICI are used broadly across stages.We performed a retrospective cohort study of adults in the U.S. Veterans Affairs (VA) medical system diagnosed with lung cancer or melanoma from 2003 to 2016. We defined antibiotic exposure as receipt of a prescription for a systemic antibacterial agent between 6 months before and 6 months after cancer diagnosis. Demographics, clinical variables, prescriptions, and diagnostic codes were abstracted from the VA Corporate Data Warehouse. Antibiotic exposure was compared using t tests, Chi-square, and multivariate analyses.A total of 310,321 patients (280,068 lung cancer, 30,253 melanoma) were included in the analysis. Antibiotic exposure was more common among patients with lung cancer (42% vs. 24% for melanoma; P.001). Among antibiotic-exposed patients, those with lung cancer were more likely to receive prescriptions for multiple antibiotics (47% vs. 30% for melanoma; P.001). In multivariate analyses, antibiotic exposure was associated with lung cancer diagnosis (HR 1.50; 95% CI, 1.46-1.55), comorbidity score (HR 1.08; 95% CI, 1.08-1.09), non-white race (HR 1.11; 95% CI, 1.06-1.17), and female gender (HR 1.31; 95% CI, 1.24-1.37).Among cancer patients, antibiotics are prescribed frequently. Antibiotic exposure is more common in certain cancer types and patient populations. Given the negative effect antibiotic exposure has on immunotherapy outcomes, these observations may have clinical and healthy policy implications.

The overall prevalence of potential drug–drug interactions (DDIs) among patients with lung cancer is unknown. The objective of this study was to determine the prevalence of potential DDIs and major DDIs among individuals newly diagnosed with lung cancer in a national cohort. We performed a retrospective cross-sectional study of adult patients in the United States Veterans’ Affairs (VA) medical system diagnosed with lung cancer between 2003 and 2016. The primary endpoint was the prevalence of prescriptions for medications associated with any potential DDIs during the 3 months leading up to and including the date of lung cancer diagnosis. The secondary endpoint was the prevalence of prescriptions associated with major DDIs during the same time period. Overall, 280,068 patients were included in the study; 55.9% of patients were prescribed medications associated with potential DDIs, while 5.3% received prescriptions for medications associated with major DDIs. Among the 20 most commonly prescribed drugs associated with potential DDIs, only two were associated with major DDIs. Medications with potential DDIs are prescribed to the majority of patients with lung cancer; however, only about 5% of patients are prescribed medications with major DDIs that might be prohibited in certain clinical trials.

In 1991, the U.S. Food & Drug Administration (FDA) approved rmetHuG-CSF for human use. This recombinant methionyl human granulocyte colony-stimulating factor, or filgrastim, saw use in over 1 million patients in its first 5 years on the market. In 2002, the FDA approved a version of filgrastim with covalent linkage to a monomethoxypolyethylene glycol, increasing the molecular size and half-life to replace multiple days of dosing with a single injection. These medications remained standard of care for neutropenia until the Biologics Price Competition and Innovation Act of 2009 created an abbreviated pathway to licensure for biologic products. Practitioners now have their pick of numerous and expanding options for pegfilgrastim biosimilars.

The overall prevalence of potential drug-drug interactions (DDIs) among patients with lung cancer is unknown.The objective of this study was to determine the prevalence of potential DDIs and major DDIs among individuals newly diagnosed with lung cancer in a national cohort.We performed a retrospective cross-sectional study of adult patients in the United States Veterans' Affairs (VA) medical system diagnosed with lung cancer between 2003 and 2016. The primary endpoint was the prevalence of prescriptions for medications associated with any potential DDIs during the 3 months leading up to and including the date of lung cancer diagnosis. The secondary endpoint was the prevalence of prescriptions associated with major DDIs during the same time period.Overall, 280,068 patients were included in the study; 55.9% of patients were prescribed medications associated with potential DDIs, while 5.3% received prescriptions for medications associated with major DDIs. Among the 20 most commonly prescribed drugs associated with potential DDIs, only two were associated with major DDIs.Medications with potential DDIs are prescribed to the majority of patients with lung cancer; however, only about 5% of patients are prescribed medications with major DDIs that might be prohibited in certain clinical trials.

Objective: To evaluate the existing literature regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in the treatment of hormone receptor–positive advanced breast cancer (ABC). Data Sources: A search of the medical literature was performed using PubMed (2014 to June 2018). Search terms included cyclin-dependent kinase, CDK, breast cancer, palbociclib, ribociclib, abemaciclib, PD0332991, LEE011, and LY2835219. Clinicaltrials.gov was also searched. Study Selection and Data Extraction: Trials with clinical efficacy outcomes evaluating CDK 4/6 inhibitors in the treatment of advanced hormone-positive breast cancer were considered. Data Synthesis: Palbociclib, abemaciclib, and ribociclib each demonstrated significant benefit when combined with an aromatase inhibitor, the benefit to patients was similar for each, with an improvement of 42% to 51% in median progression-free survival (PFS). In combination with fulvestrant, CDK 4/6 inhibitors used for the treatment of hormone receptor–positive ABC resulted in a 43% to 58% improvement in median PFS versus fulvestrant alone. CDK inhibitors are relatively well tolerated; however, discontinuation as a result of adverse effects was highest with abemaciclib. Relevance to Patient Care and Clinical Practice: This review considers the use of the 3 commercially available CDK 4/6 inhibitors for treatment of hormone receptor–positive breast cancer, including data on each of the 3 agents in newly advanced and treatment refractory disease. Conclusions: The CDK inhibitors should be used in combination with endocrine therapies for the treatment of ABC. Efficacy of the 3 agents is similar. Selection within the class should include consideration of adverse effects and drug interactions.

Background: There is growing interest in the bio-refining of foliage grasses to yield a range of industrial raw products. The aim of this research was to evaluate if aqueous extracts from grasses have the potential to act as crop bio-stimulants by assessing their defence elicitor activity.Results: Field-grown foliage (500 g fresh weight) from the Lolium perenne varieties Tyrella, Dromara, Abermagic, and Spelga were homogenised in water (2 l) and the run-off liquid filtered through Whatman No. 1 filter paper before freezing. Thawed filtrate was centrifuged at 21,000 rpm for 15 min, to give pellet and supernatant fractions, which were assayed separately for defence elicitor activity by adding them to cell suspension cultures of Phaseolus vulgaris in the early exponential phase of growth (7–10 days into a 14 days culture passage). Elicitor activity was evaluated 24 h after treatment by assessing the extent of necrosis (browning) in the P. vulgaris cells. Supernatant and pellet fractions of all four L. perenne varieties were found to have potent cell defence elicitor activity, although there were relatively small but significant differences between the varieties. In a second series of extractions, homogenisation of tissues in water was compared with screw-pressed juice using the varieties, Malone, Seagoe, and Copeland. Varietal differences in elicitor activity of these extracts were removed if they were first equalised for protein content prior to eliciting the bean cells, although the screw-pressed juice was marginally more active as an elicitor than the homogenised extract. Autoclaving the extracts in attempts to solubilise/release additional elicitor compounds neither increased nor decreased the elicitor activities of the supernatant or pellet fractions. Elicitor activity of the extract was partially reduced by treating with a cation exchange resin, almost entirely removed by adsorption onto activated carbon and completely abolished by ashing at 650 °C.Conclusion: The L. perenne defence elicitor(s) is therefore organic rather than inorganic, heat-stable, cationic at neutral pH, and readily soluble in water at room temperature.

The adventitious bud forming ability of Sitka spruce (Picea sitchensis (Bong.) Carr.) buds in vitro was found to be dependent upon the age of tree from which the explants were taken. Bud formation declined exponentially with increasing tree age when 1.0 and 10 μM 6-benzylaminopurine (BA) were used to induce adventitious buds. When less BA was used (0.1 μM) bud production was much lower with all ages of tree and no mathematical relationship between declining bud production and tree age was found. By a tree age of 6 years bud-forming ability had declined severely. Even the few buds that developed on older tree tissues failed to elongate into shoots, became necrotic and eventually died, indicating that adventitious bud induction in this species is not a rejuvenative process. Callusing of bud explants also declined with increasing tree age when 0.1 μM BA was used whilst very little callusing occurred at the higher cytokinin concentrations (1.0 and 10 μM BA). Tissue necrosis in vitro increased with tree age, whilst the ability of BA to retard necrosis declined with increasing tree age. Buds from epicormic shoots, formed on the lower trunks of 20-year-old trees when these were exposed to light, were not significantly better at forming adventitious buds in vitro than buds taken from the lower branches of the crown.

David Douglas, when he first described Picea sitchensis wrote “It has the great advantage that it thrives on poor soils and could become a large and useful tree in Great Britain”. It has since become the most extensively planted exotic species in Great Britain after its introduction by Douglas in 1831 from its native range in the west coast fog belt of North America.

The contribution of non-ionizing radiation to synfuel-related skin carcinogenesis is largely unknown. We have employed a modification of the Salmonella histidine reversion test system to detect photomutation by various fuel substances. For photomutation testing we washed and resuspended cells in buffer, irradiated with 'visible' light in the presence of test substance, and removed aliquots after various light exposures for assay by the plate incorporation method. We have assayed photomutagenicity and microsome-mediated mutagenicity of a crude petroleum, a shale oil, and coal hydrogenation process intermediates. Photomutagenicity was studied using one concentration of each oil; peak revertants per plate for most oils tested were relatively similar to revertants per plate with microsomal activation of the same oil at the corresponding concentration. The shale oil was an exception to this pattern: with light activation, peak revertant numbers per plate were approximately 10 times the value observed with microsomal activation. The samples tested are not assumed to be representative of all petroleums, shale oils or coal oils. Our results do suggest that environmental radiation may be a significant factor in synfuel-related skin carcinogenesis and that photomutagens may be different from enzyme-activatable promutagens.

Suspension cultures of Phaseolus vulgaris accumulated phytoalexins after treatment with an extract of bean hypocotyls. Maximum production of phaseollin occurred during the early exponential phase of culture growth. Phaseollin was converted to phaseollinosoflavan by these cultures and this conversion occurred during accumulation of the phytoalexins. Factors affecting phytoalexin accumulation in these cultures are discussed.

— The UV-B region (280–320 nm) is thought to be primarily responsible for the mutagenic, lethal, and carcinogenic effects of solar radiation. We have conducted UV-B action spectroscopy for mutagenesis and survival of Ames' Salmonella typhimurium strain TA98 (uvrB, pKM101) using both monochromatic radiation from a dye laser and broader bandwidth radiation emitted from FS-20 sunlamps. A series of optical filters having different transmission cut-offs together with the sunlamp source provided bandwidths having successively less short wavelength components from which a “broad band” action spectrum was deduced. The two sets of action spectra differed both qualitatively and quantitatively: in comparison to the monochromatic action spectra, the “broad band” spectra showed up to a 200-fold reduced efficiency for both mutation induction and lethality by UV-B wavelengths. These results suggest a large protective effect of the background UV-A and/or visible radiations which were present during the broad spectrum irradiations and which are also present in solar radiation. Additional experiments show that to the extent tested this protective effect is not due to photo-reactivation or irradiance (dose rate) effects