Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy.

Many patients diagnosed with cancer adopt dietary changes and supplement use, and a growing body of evidence suggests that such modifications can affect outcomes to cancer therapy. We sought to assess the prevalence of these practices and the surrounding physician-patient dialogue among patients with metastatic renal cell carcinoma. An online survey was administered by Kidney Cancer Research Alliance (KCCure), interrogating dietary modification patterns, supplement usage, out-of-pocket expenditure related to supplements, and patients' views toward alternative medicine practices. Patients with metastatic renal cell carcinoma receiving combination therapy were actively solicited. In total, 289 unique responses were collected. The most common first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). Within the cohort, 147 (50.9%) started using supplements following diagnosis of renal cell carcinoma; the most utilized supplements were probiotics, cannabidiol (CBD) oil/marijuana, and Vitamin C, reported by 70 (47.6%), 61 (41.4%), and 54 (36.7%), respectively. Dietary modifications following cancer diagnosis were reported by 101 (34.9%) respondents, of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. Most respondents (71.3%) noted that they consistently report supplement usage to their physicians. A substantial proportion of patients with metastatic renal cell carcinoma utilize dietary modification and supplements as an adjunct to antineoplastic therapy. Considering the widespread adoption of these practices and the reported effects on cancer treatment, it is crucial for healthcare providers to engage in discussions with patients regarding supplement use.

Food contamination from packaging material with special focus on the Bisphenol-A.

Additives, such as bisphenol A (BPA) that are added to packaging material to enhance functionality may migrate into food products creating a concern for food safety. BPA has been linked to various chronic diseases, such as: diabetes, obesity, prostate cancer, impaired thyroid function, and several other metabolic disorders. To safeguard consumers, BPA migration limits have been defined by regulatory bodies. However, it is important to address the underlying factors and mechanisms so that they can be optimized in order to minimize BPA migration. In this review, we determine the relative importance of the factors, i.e. temperature, contact time, pH, food composition, storage time and temperature, package type, cleaning, and aging, and packaging damage that promote BPA migration in foods. Packaging material seems to be the key source of BPA and the temperature (applied during food production, storage, can sterilization and cleaning processes) was the critical driver influencing BPA migration.

Barriers to Clinical Trial Implementation Among Community Care Centers.

Importance: While an overwhelming majority of patients diagnosed with cancer express willingness to participate in clinical trials, only a fraction will enroll onto a research protocol. Objective: To identify critical barriers to trial enrollment to translate findings into actionable practice changes that increase cancer clinical trial enrollment. Design, Setting, and Participants: This survey study included designated site contacts at oncology practices with teams who were highly involved with the Association of Community Cancer Centers (ACCC) Community Oncology Research Institute (ACORI) clinical trials activities, all American Society of Clinical Oncology (ASCO)-ACCC collaboration pilot sites, and/or sites providing care to at least 25% African American and Hispanic residents. To determine participation trends among health care practices in oncology-focused research, identify barriers to clinical trial implementation and operation, and establish unmet needs for cancer clinics interested in trial participation, a 34-question survey was designed. Survey questions were defined within 3 categories: cancer center demographic characteristics, clinical trial characteristics, and referral practices. The survey was distributed through email and was open from June 20 through October 5, 2022. Main Outcomes and Measures: Participation in and barriers to conducting oncology trials in different community oncology settings. Results: The survey was distributed to 100 cancer centers, with completion by 58 centers (58%) across 25 states. Fifty-two centers (88%) reported that they conduct therapeutic clinical trials, of which 33 (63%) were from urban settings, 11 (21%) were from suburban settings, and 8 (15%) were from rural settings. Only 25% of rural practices (2 of 8) offered phase 1 trials, compared with 67% of urban practices (22 of 33) (P = .01). Respondents noted challenges in conducting research, including patient recruitment (27 respondents [52%]), limited staffing (27 [52%]), and nonrelevant trials for their patient population (25 [48%]). Among sites not offering therapeutic trials, barriers to research conduct included limited infrastructure, funding, and staffing. Most centers (46 of 58 [79%]) referred patients to outside centers for clinical trial enrollment, particularly in the context of late-stage disease and/or disease progression. Only 17 of these sites (37%) had established protocols for patient follow-up subsequent to outside referral. Conclusions and Relevance: In this national survey study of barriers to clinical trial implementation, most sites offered therapeutic trials, but there were significant disparities in trial availability across care settings. Furthermore, fundamental deficiencies in trial support infrastructure limited research activity, including within programs currently conducting research as well as at sites interested in future clinical research opportunities. These results identify crucial unmet needs for oncology clinics to effectively offer clinical trials to patients seeking care.

Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor-based Combinations.

BACKGROUND AND OBJECTIVE: The impact of time of metastasis onset with respect toprimary renal cell carcinoma (RCC) diagnosis on survival outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assessed differences in clinical outcomes between synchronous and metachronous metastatic RCC (mRCC). METHODS: Data for patients with mRCC treated with first-line ICI-based combination therapies between 2014 and 2023 were retrospectively collected. Patients were categorized as having synchronous metastasis if present within 3 mo of RCC diagnosis; metachronous metastasis was defined as metastasis >3 mo after primary diagnosis. Time to treatment failure (TTF), overall survival (OS), and the disease control rate (DCR) were assessed. KEY FINDINGS AND LIMITATIONS: Our analysis included 223 eligible patients (126 synchronous and 97 metachronous). Median TTF did not significantly differ between the synchronous and metachronous groups (9 vs 19.8 mo; p = 0.063). Median OS was significantly shorter in the synchronous group (28.0 vs 50.9 mo; p = 0.001). Similarly, patients with synchronous metachronous metastasis (58.7% vs. 78.4%; p = 0.002). On multivariable analyses, synchronous metastasis remained independently associated with worse OS and DCR. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this hypothesis-generating study, patients with mRCC with synchronous metastasis who were treated with first-line ICI-based combinations have a poorer OS and worse DCR than those with metachronous mRCC. If these results are externally validated, time to metastasis could be included in prognostic models for mRCC. PATIENT SUMMARY: Our study demonstrates that patients treated with current first-line immunotherapies, who present with metastasis at the initial diagnosis of kidney cancer have worse overall survival compared to those who develop metastasis later. These results can help physicians and patients understand life expectancy.

Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations.

PURPOSE: There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB. RESULTS: Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients. CONCLUSION: Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.

Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant Prostate Cancer.

The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC. The primary endpoint was differences in CD4+ and CD8+ T-cell infiltrate in 8-week versus baseline bone metastasis biopsies; secondary endpoints were safety, radiographic progression-free survival (rPFS), and overall survival (OS). Of the 42 treated patients (29 R223+P, 13 R223), 18 R223+P and 8 R223 patients had evaluable paired tumor biopsies. Median fold-change of CD4+ T cells was -0.7 (range: -9.3 to 4.7) with R223+P and 0.1 (-11.1 to 3.7) with R223 (P = 0.66); for CD8+ T cells, median fold-change was -0.6 (-7.4 to 5.3) with R223+P and -1.3 (-3.1 to 4.8) with R223 (P = 0.66). Median rPFS and OS was 6.1 (95% confidence interval: 2.7-11.0) and 16.9 months [12.7-not reached (NR)], respectively, with R223+P and 5.7 (2.6-NR) and 16.0 (9.0-NR), respectively, with R223. Although R223+P was well tolerated with no unexpected toxicity, the combination did not improve efficacy. High-dimensional flow cytometry demonstrated minimal immune modulation with R223, whereas R223+P induced CTLA-4 expression on circulating CD4+ T cells. Clinical responders possessed lower circulating frequencies of Ki67+ T and myeloid cells at baseline and higher circulating frequencies of TIM-3+ T and myeloid cells by week 9. Although R223+P did not induce T-cell infiltration into the tumor microenvironment, exhaustion of induced peripheral T-cell immune responses may dampen the combination's clinical activity.

Nutritional and functional perspectives of pseudocereals.

An increase in the consumption of carbohydrate-rich cereals over past few decades has led to increased metabolic disorders in population. This nutritional imbalance in diets may be corrected by substituting cereal grains with pseudocereals that are richer in high-quality proteins, dietary fibers, unsaturated fats, and bioactive compounds (e.g., polyphenols and phytosterols) as compared to cereal grains. These nutrients have been associated with numerous health benefits, such as hypolipidemic, anti-inflammatory, anti-hypertensive, anti-cancer, and hepatoprotective properties, and benefits against obesity and diabetes. In this review, the nutritional composition and health benefits of quinoa, amaranth, and buckwheat are compared against wheat, maize, and rice. Subsequently, the processing treatments applied to quinoa, amaranth, and buckwheat and their applications into food products are discussed. This is relevant since there is substantial market potential for both pseudocereals and functional foods formulated with pseudocereals. Despite clear benefits, the current progress is slowed down by the fact that the cultivation of these pseudocereals is limited to its native regions. Therefore, to meet the global needs, it is imperative to support worldwide cultivation of these nutrient-rich pseudocereals.

Integrated smart dust monitoring and prediction system for surface mine sites using IoT and machine learning techniques.

The mining industry confronts significant challenges in mitigating airborne particulate matter (PM) pollution, necessitating innovative approaches for effective monitoring and prediction. This research focuses on the design and development of an Internet of Things (IoT)-based real-time monitoring system tailored for PM pollutants in surface mines, specifically PM 1.0, PM 2.5, PM 4.0, and PM 10.0. The novelty of this work lies in the integration of IoT technology for real-time measurement and the application of machine learning (ML) techniques for accurate prediction based on recorded dust pollutants data. The study's findings indicate that PM 1.0 pollutants exhibited the highest concentration in the atmosphere of the ball clay surface mine sites, with the stockyard site registering the maximum levels of PM pollutants (28.45 µg/m3, 27.89 µg/m3, 26.17 µg/m3, and 27.24 µg/m3, respectively) due to the dry nature of clay materials. Additionally, the research establishes four ML models-Decision Tree (DT), Gradient Boosting Regression (GBR), Random Forest (RF), and Linear Regression (LR)-for predicting PM pollutant concentrations. Notably, Random Forest demonstrates superior performance with the lowest Mean Absolute Error (MAE) and Root Mean Squared Error (RMSE) at 1.079 and 1.497, respectively. This comprehensive solution, combining IoT-based monitoring and ML-based prediction, contributes to sustainable mining practices, safeguarding worker well-being, and preserving the environment.

Development of injectable upconversion nanoparticle-conjugated doxorubicin theranostics electrospun nanostructure for targeted photochemotherapy in breast cancer.

Nanotheranostic-based photochemotherapies with targeted drug delivery have considerably surfaced in cancer therapy. In the presented work, polyethyleneimine-coated upconversion nanoparticles were engineered to conjugate covalently with doxorubicin. Upconversion nanoparticles (UCNP)-Doxorubicin (DOX)/synthesized epidermal growth factor receptor-targeting peptide blended with polymer composite was electrospun and formulated as the injectable dosage form. The size of the UCNP and the nanofiber diameter were assessed as 26.75 ± 1.54 and 162 ± 2.82 nm, respectively. The optimized ratio of dopants resulted in UCNP photoluminescence with maximum emission intensity at around 800 nm upon 980 nm excitation wavelength. The paramagnetic nature of UCNPs and amide conjugation with the drug was confirmed analytically. The loading capacity of UCNP for doxorubicin was determined to be 54.56%, while nanofibers exhibited 98.74% capacity to encapsulate UCNP-DOX. The release profile of UCNP-DOX from nanofiber formulation ranged from sustained to controlled, with relative enhancement in acidic conditions. The nanofiber demonstrated good mechanical strength, robust swelling, and degradation rate. Biocompatibility tests showed more than 90% cell viability on L929 and NIH/3T3 cell lines with UCNP-DOX@NF/pep nanoformulation. The IC50 values of 2.15 ± 0.54, 2.87 ± 0.67, and 3.42 ± 0.45 µg/mL on MDA-MB-231, 4T1, and MCF-7 cancer cell line, respectively, with a significant cellular uptake, has been reported. The UCNP protruded a ≈62.7°C temperature rise within 5 min of 980 nm laser irradiation and a power density of 0.5 W cm-2. The nanoformulation induced reactive oxygen species of 65.67% ± 3.21% and apoptosis by arresting the cell cycle sub-G1 phase. The evaluation conveys the effectiveness of the developed injectable theranostic delivery system in cancer therapy.

Multifunctional Dy2NiMnO6/Reduced Graphene Oxide Nanocomposites and Their Catalytic, Electromagnetic Shielding, and Electrochemical Properties.

Multifunctional nanocomposites have shown great interest in clean energy systems and environmental applications in recent years. Herein, we first reported the synthesis of Dy2NiMnO6 (DNMO)/reduced graphene oxide (rGO) nanocomposites utilizing a hybrid approach involving sol-gel and solvothermal processes. Subsequently, we investigated these nanocomposites for their applications in catalysis, electromagnetic interference shielding, and supercapacitors. A morphological study suggests spherical-shaped DNMO nanoparticles of an average size of 382 nm that are uniformly distributed throughout the surface without any agglomeration. The as-prepared nanocomposites were used as catalysts to investigate the catalytic reduction of 4-nitrophenol in the presence of NaBH4. DNMO/rGO nanocomposites demonstrate superior catalytic activity when compared with bare DNMO, with the rate of reduction being influenced by the composition of the DNMO/rGO nanocomposites. In addition, novel multifunctional DNMO/rGO was incorporated into polyvinylidene difluoride (PVDF) to develop a flexible nanocomposite for electromagnetic shielding applications and exhibited a shielding effectiveness of 6 dB with 75% attenuation at a frequency of 8.5 GHz compared to bare PVDF and PVDF-DNMO nanocomposite. Furthermore, the electrochemical performance of DNMO/rGO nanocomposites was investigated as an electrode material for supercapacitors, exhibiting the highest specific capacitance of 260 F/g at 1 A/g. These findings provide valuable insights into the design of DNMO/rGO nanocomposites with remarkable performance in sustainable energy and environmental applications.

Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer and Response to Checkpoint Inhibition.

This single-center cohort study assesses the association of tumor mutational burden status in patients with metastatic castration-resistant prostate cancer and response to immune checkpoint inhibitor therapy.

Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.

BACKGROUND: AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. METHODS: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. RESULTS: In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%). CONCLUSION: In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.

Production, optimization, scale up and characterization of polyhydoxyalkanoates copolymers utilizing dairy processing waste.

The microbial biotransformation using low-cost feedstock to produce biopolymers (degradable), an alternative to petrochemical-based synthesis plastics (non-degradable), can be a beneficial approach towards sustainable development. In this study, the dairy industry processes waste (whey) is used in polyhydroxyalkanoate (PHA) copolymer production. Initial screening suggested that Ralstonia eutropha produced higher PHA as compared to Bacillus megaterium. A central composite rotatable design-based optimization using two process variables (amino acid and tween-80) concentration remarkably influenced PHA co-polymer production under physiological conditions of pH (7), temperature (37 °C), and agitation rate of 150 rpm. High polyhydroxybutyrate (PHB) mass fraction yield of 69.3% was observed as compared to predicted yield of 62.8% from deproteinized whey as feed. The combination of tryptophan (50 mg L-1) and tween-80 (3 mL-1) enhanced R. eutropha mass gain to 6.80 g L-1 with PHB contents of 4.71 g L-1. Further, characterization of PHA and its copolymers was done by ESI-MS, FTIR, and TEM. On upscaling up to 3.0 L, the PHA contents and yields were noted as quite similar by R. eutropha. This study demonstrates that dairy waste processing waste can be potentially utilized as inexpensive feed for producing high content of biopolymers to develop a sustainable system of waste management.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Synthesis and glutathione peroxidase (GPx)-like activity of selenocystine (SeC) bioconjugates of biotin and lipoic acid.

The conjugation of active biomolecules provides insight into their bioreactivity, leading to many applications in biotechnology and materials science. Herein, we report L-selenocystine (SeC) bioconjugates of lipoic acid (universal antioxidant) and biotin (Vitamin-H). The SeC-bioconjugates, SeC-Biotin (1) and SeC-Lipoic acid (2) were synthesized using solid phase peptide synthesis (SPPS) method and were characterized by multinuclear 1D (1H, 13C, 77Se) and 2D (1H-1H COSY and 1H-13C TOCSY) NMR spectroscopy, ESI-MS spectrometry, and RP-HPLC. The GPx-like enzyme mimicking activity of the SeC-bioconjugates 1 and 2 has been investigated through the coupled reductase assay method for the catalytic reductions of hydrogen peroxide into water. A significant enhancement in GPx-like enzymatic activity was observed for both novel bioconjugates SeC-Biotin (1) and SeC-Lipoic acid (2) as compared to diphenyl diselenide (Ph2Se2), L-selenocystine (SeC), biotin, lipoic acid, and ebselen.

Growth Kinetics of Prodigiosin (Food Color) Produced by Novel Serratia marcescens bhu prodig Under Submerged Fermentation (SMF).

Prodigiosin is a promising food color due to its antibacterial, antimalarial, antimycotic characteristics, immunomodulating, and antitumor activities. Novel prodigiosin producing strain isolated from sugarcane field soil of Banaras Hindu University, India, characterized as Serratia marcescens bhu prodig by 16 sRNA. The effect of carbon, nitrogen source, and physical parameters (pH and temperature) on pigment yield was studied. The highest amount of pigment produced, which was 800.95 ± 0.05 mg/L, was detected when sorbitol and peptone were used as nitrogen and carbon source with pH 7 at 30 °C. The optimized condition scale-up in a bioreactor with a working capacity of 3.0 L, gave maximum pigment yield of 825 ± 0.05 mg/L with µ (Maximum specific growth rate), Yp/x, which represents the product yield coefficient, and Yp/s, which signifies the specific product yield coefficient and productivity of 0.3/h, 0.62, 0.80, and 0.02 g/L/h, respectively, after 72 h of cultivation in submerged fermentation (SMF). The isolated pigment was characterized as prodigiosin by the analysis of spectral data and GC-MS. The mass spectrophotometry investigation characterized pigment as 4-methoxy-5(5 methyl-4-pentyl-2H-pyrrol-2-ylidene)- 2,2-bipyrrole ring structure. The GC-MS chromatogram showed m/z of 323, representing prodigiosin. The prodigiosin yield and productivity obtained in the current finding were higher than in previous reports.

Synthesis and screening for anticancer activity of two novel telluro-amino acids: 1,3-Tellurazolidine-4-carboxylic acid and tellurohomocystine.

Tellurium (Te) containing amino acids and their derivatives have the potential to participate in biological processes, which are currently being studied extensively to understand the function of Te in biological and pharmacological activities. Here, we are reporting the synthesis of two novel Te-containing unnatural amino acids; 1,3-Tellurazolidine-4-carboxylic acid [Te{CH2CH(COOH)NHCH2}] 5, and 4,4'-(1,2-Ditellurdiyl)bis(2-aminobutanoic acid), i.e., tellurohomocystine [TeCH2CH2CH(NH2)COOH]2 7, synthesized from tellurocystine, and L-methionine as precursors, respectively. These telluro-amino acids were thoroughly characterized by multinuclear (1H, 13C, 125Te) NMR spectroscopy, high-resolution ESI-mass spectrometry (ESI-MS), and elemental analysis. The telluro-amino acids 5 and 7 demonstrated good biocompatibility when in vitro cytotoxicity was analyzed on two fibroblast cell lines L929 and NIH/3T3. The treatment of telluro-amino acids 1,3-Tellurazolidine-4-carboxylic acid 5 and tellurohomocystine 7 on breast cancer cell line MCF-7 showed anticancer activity with IC50 values of 7.29 ± 0.27 µg/mL and 25.36 ± 0.12 µg/mL, respectively. The cell cycle distribution studies also revealed arrest at the sub-G1 phase suggesting telluro-amino acids to be apoptotic.

FGFR Inhibition: Understanding and Overcoming Resistance.

SUMMARY: Facchinetti and colleagues provide key insights into the evolution of resistance to fibroblast growth factor receptor (FGFR) inhibitors, including the development of kinase domain mutations and activation of the PI3K-AKT signaling axis. In a separate study, Subbiah and colleagues report extensive preclinical data and initial clinical data for RLY-4008, an FGFR2-selective inhibitor that is poised to minimize toxicity and overcome resistance through greater potency and selectivity. See related article by Facchinetti et al., p. 1998 (5). See related article by Subbiah et al., p. 2012 (7).