Journal articles: 'CBR AGENTS'

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Heras, Stella, Vicente Botti, and Vicente Julián. "Challenges for a CBR framework for argumentation in open MAS." Knowledge Engineering Review 24, no. 4 (December 2009): 327–52. http://dx.doi.org/10.1017/s0269888909990178.

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AbstractNowadays, Multi-Agent Systems (MAS) are broadening their applications to open environments, where heterogeneous agents could enter into the system, form agents’ organizations and interact. The high dynamism of open MAS gives rise to potential conflicts between agents and thus, to a need for a mechanism to reach agreements. Argumentation is a natural way of harmonizing conflicts of opinion that has been applied to many disciplines, such as Case-Based Reasoning (CBR) and MAS. Some approaches that apply CBR to manage argumentation in MAS have been proposed in the literature. These improve agents’ argumentation skills by allowing them to reason and learn from experiences. In this paper, we have reviewed these approaches and identified the current contributions of the CBR methodology in this area. As a result of this work, we have proposed several open issues that must be taken into consideration to develop a CBR framework that provides the agents of an open MAS with arguing and learning capabilities.

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Robertson, Gregory T., Eric J. Bonventre, Timothy B. Doyle, Qun Du, Leonard Duncan, Timothy W. Morris, Eric D. Roche, Dalai Yan, and A. Simon Lynch. "In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Studies of the Mode of Action in Staphylococcus aureus." Antimicrobial Agents and Chemotherapy 52, no. 7 (July 2008): 2313–23. http://dx.doi.org/10.1128/aac.01649-07.

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ABSTRACT Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.

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Navarro, M., S. Heras, V. Julián, and V. Botti. "Incorporating temporal-bounded CBR techniques in real-time agents." Expert Systems with Applications 38, no. 3 (March 2011): 2783–96. http://dx.doi.org/10.1016/j.eswa.2010.08.070.

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Aydin, Burc. "Global Characteristics of Chemical, Biological, and Radiological Poison Use in Terrorist Attacks." Prehospital and Disaster Medicine 35, no. 3 (April 2, 2020): 260–66. http://dx.doi.org/10.1017/s1049023x20000394.

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AbstractBackground:Chemical, biological, and radiological (CBR) terrorism continues to be a global threat. Studies examining global and historical toxicological characteristics of CBR terrorism are lacking.Methods:Global Terrorism Database (GTD) and RAND Database of Worldwide Terrorism Incidents (RDWTI) were searched for CBR terrorist attacks from 1970 through 2017. Events fulfilling terrorism and poisoning definitions were included. Variables of event date and location, event realization, poisonous agent type, poisoning agent, exposure route, targets, connected events, additional means of harm, disguise methods, poisonings, and casualties were analyzed along with time trends and data gaps.Results:A total of 446 events of CBR terrorism were included from all world regions. A trend for increased number of events over time was observed (R2 = 0.727; coefficient = 0.511). In these attacks, 4,093 people lost their lives and 31,903 were injured. Chemicals were the most commonly used type of poison (63.5%). The most commonly used poisonous agents were acids (12.3%), chlorine or chlorine compounds (11.2%), riot control agents (10.8%), cyanides (5.8%), and Bacillus anthracis (4.9%). Occurrence of poisoning was confirmed in 208 events (46.6%). Most common exposure routes were skin, mucosa, or eye (57.2%) and inhalation (47.5%). Poison was delivered with additional means of harm in 151 events (33.9%) and in a disguised way in 214 events (48.0%), respectively.Conclusions:This study showed that CBR terrorism is an on-going and increasingly recorded global threat involving diverse groups of poisons with additional harmful mechanisms and disguise. Industrial chemicals were used in chemical attacks. Vigilance and preparedness are needed for future CBR threats.

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Oltenfreiter, Ruth, Ludovicus Staelens, Soraya Labied, Veerle Kersemans, Francis Frankenne, Agnes Noël, Christophe Van de Wiele, and Guido Slegers. "Tryptophane-Based Biphenylsulfonamide Matrix Metalloproteinase Inhibitors as Tumor Imaging Agents." Cancer Biotherapy and Radiopharmaceuticals 20, no. 6 (December 2005): 639–47. http://dx.doi.org/10.1089/cbr.2005.20.639.

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Hosseinimehr, Seyed Jalal. "Potential Utility of Radioprotective Agents in the Practice of Nuclear Medicine." Cancer Biotherapy and Radiopharmaceuticals 24, no. 6 (December 2009): 723–31. http://dx.doi.org/10.1089/cbr.2009.0635.

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Rosebrough, S. F., and D. F. Hartley. "Isothiocyanate-Trigalactose: Application for Antibody-Targeted Delivery of Diagnostic and Therapeutic Agents." Cancer Biotherapy and Radiopharmaceuticals 15, no. 5 (October 2000): 507–15. http://dx.doi.org/10.1089/cbr.2000.15.507.

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Ahmed, Ishtiaq, Saif Ur Rehman, Shiva Shahmohamadnejad, Muhammad Anjum Zia, Muhammad Ahmad, Muhammad Muzammal Saeed, Zain Akram, Hafiz M. N. Iqbal, and Qingyou Liu. "Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders." Molecules 26, no. 11 (June 3, 2021): 3389. http://dx.doi.org/10.3390/molecules26113389.

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In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

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Sharma, Rakesh Kumar, Sudha Rana, and Natarajan Gopalan. "Towards Protecting Critical National Assets and Preparedness for Response to Hazardous Chemical, Biological and Radiological Attacks." Defence Life Science Journal 4, no. 4 (October 21, 2019): 256–65. http://dx.doi.org/10.14429/dlsj.4.15134.

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Hazardous chemical, biological and radiological (CBR) materials are catching attention of unscrupulous actors for creating terror and havoc. Threat perception for use of such materials by terrorists and non-state actors for malicious purposes, is not imaginative but real and imminent in today’s context. World has witnessed a number of such incidences in the recent years, e.g., Mustard gas attack against Kurdish forces in Iraq; ricin laced letters sent to US President and others senators; use of Nerve gas agents in Syria; capturing of Uranium from University of al- Mousal, Iraq by IS, etc. National assets like critical buildings where main legislative, historical building, Hospitals are some of the likely targets for CBR attacks attract quick coverage by media. Authorities related with managing and safeguarding mechanisms of the facilities to prevent such events happening also to enhance their capabilities as well as effective response. Essential CBR security should include measures to rapidly detect and effectively deter the CBR incidences their deleterious consequences. In this review, protection of the critical facilities from CBR attacks and capacity in terms of infrastructure, specialised training and mutual aid have been discussed.

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Robertson, Gregory T., Timothy B. Doyle, Qun Du, Leonard Duncan, Khisimuzi E. Mdluli, and A. Simon Lynch. "A Novel Indole Compound That Inhibits Pseudomonas aeruginosa Growth by Targeting MreB Is a Substrate for MexAB-OprM." Journal of Bacteriology 189, no. 19 (July 20, 2007): 6870–81. http://dx.doi.org/10.1128/jb.00805-07.

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ABSTRACT Drug efflux systems contribute to the intrinsic resistance of Pseudomonas aeruginosa to many antibiotics and biocides and hamper research focused on the discovery and development of new antimicrobial agents targeted against this important opportunistic pathogen. Using a P. aeruginosa PAO1 derivative bearing deletions of opmH, encoding an outer membrane channel for efflux substrates, and four efflux pumps belonging to the resistance nodulation/cell division class including mexAB-oprM, we identified a small-molecule indole-class compound (CBR-4830) that is inhibitory to growth of this efflux-compromised strain. Genetic studies established MexAB-OprM as the principal pump for CBR-4830 and revealed MreB, a prokaryotic actin homolog, as the proximal cellular target of CBR-4830. Additional studies establish MreB as an essential protein in P. aeruginosa, and efflux-compromised strains treated with CBR-4830 transition to coccoid shape, consistent with MreB inhibition or depletion. Resistance genetics further suggest that CBR-4830 interacts with the putative ATP-binding pocket in MreB and demonstrate significant cross-resistance with A22, a structurally unrelated compound that has been shown to promote rapid dispersion of MreB filaments in vivo. Interestingly, however, ATP-dependent polymerization of purified recombinant P. aeruginosa MreB is blocked in vitro in a dose-dependent manner by CBR-4830 but not by A22. Neither compound exhibits significant inhibitory activity against mutant forms of MreB protein that bear mutations identified in CBR-4830-resistant strains. Finally, employing the strains and reagents prepared and characterized during the course of these studies, we have begun to investigate the ability of analogues of CBR-4830 to inhibit the growth of both efflux-proficient and efflux-compromised P. aeruginosa through specific inhibition of MreB function.

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Aziz, Emad F., Joseph E. Bugaj, Gül Caglar, Ludger M. Dinkelborg, and Rüdiger Lawaczeck. "Novel Approach in Radionuclide Tumor Therapy: Dose Enhancement by High Z-Element Contrast Agents." Cancer Biotherapy and Radiopharmaceuticals 21, no. 3 (June 2006): 181–93. http://dx.doi.org/10.1089/cbr.2006.21.181.

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Kumar, Pardeep, Sushil Kumar Tripathi, Chang-Po Chen, Neil Mehta, Bishnuhari Paudyal, Eric Wickstrom, and Mathew L. Thakur. "Evaluation of a PACAP Peptide Analogue Labeled with 68Ga Using Two Different Chelating Agents." Cancer Biotherapy and Radiopharmaceuticals 31, no. 1 (February 2016): 29–36. http://dx.doi.org/10.1089/cbr.2015.1947.

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Capala, Jacek, Julie A. Hong, Bhadrasain Vikram, and C. Norman Coleman. "Neutron Capture Therapy: The Promise of Novel Agents and Medical Facility-Based Neutron Sources." Cancer Biotherapy and Radiopharmaceuticals 38, no. 3 (April 1, 2023): 141–42. http://dx.doi.org/10.1089/cbr.2022.0098.

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Akbashev, Mikhail Y., Brian Michael Lingerfelt, Yuan Liu, Omer Kucuk, Viraj A. Master, and Wayne Harris. "Utility of the modified Glasgow prognostic score in patients with metastatic renal cell carcinoma treated with targeted agents." Journal of Clinical Oncology 30, no. 5_suppl (February 10, 2012): 441. http://dx.doi.org/10.1200/jco.2012.30.5_suppl.441.

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441 Background: The modified Glasgow prognostic score (mGPS) is a pre-treatment prognostic system based on inflammatory biomarkers that is comparable in accuracy to the Memorial Sloan-Kettering Cancer Center (MSKCC) score for patients with metastatic renal cell carcinoma (mRCC) treated with cytokines. However, data are limited regarding the current utility of prognostic models developed in the cytokine era. In this study we examined the correlation between pre-treatment and post-treatment mGPS values and clinical benefit response (CBR) in patients treated with targeted agents for mRCC. Methods: After obtaining approval from the Emory Institutional Review Board, mGPS values were determined retrospectively using published methods and measurements of serum C-reactive protein (CRP) and serum albumin from patients who received targeted therapy for mRCC of any histology at the Emory Winship Cancer Institute between January 1, 2005 and June 30, 2011. CBR was defined as complete response (CR), partial response (PR) and stable disease (SD). Inclusion criteria included availability of at least 3 CRP values per patient. Results: Of the 635 patients who were screened, 56 were found to meet inclusion criteria. Of these, 43 received one evaluable line(s) of therapy (ELOT), 9 received two, 3 received three and 1 received four. The 74 ELOT included temsirolimus (16), sunitinib (20), sorafenib (14), pazopanib (20), everolimus (3) and bevacizumab/interferon (1). The correlation of post-treatment mGPS values to CBR was greater than pre-treatment mGPS values with sensitivity (81%), specificity (87%), positive predictive value (85%) and negative predictive value (83%). The p values were <0.001 for each parameter. Conclusions: Although these data require prospective validation, they provide evidence for the prognostic utility of mGPS assessments before and after therapy with targeted agents. Of note, the likelihood of having a CBR was much greater in patients who achieved or maintained an mGPS value of 0 after therapy. If confirmed, serial assessments of the mGPS to determine inflammatory response rates may prove to be a valuable and cost effective tool for patient care and drug development in mRCC.

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Henriet, Julien, Christophe Lang, Ronnie Muthada Pottayya, and Karla Breschi. "A SELF-ADAPTABLE DISTRIBUTED CBR VERSION OF THE EQUIVOX SYSTEM." Biomedical Engineering: Applications, Basis and Communications 28, no. 04 (August 2016): 1650028. http://dx.doi.org/10.4015/s1016237216500289.

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Three dimensional (3D) voxel phantoms are numerical representations of human bodies, used by physicians in very different contexts. In the controlled context of hospitals, where from 2 to 10 subjects may arrive per day, phantoms are used to verify computations before therapeutic exposure to radiation of cancerous tumors. In addition, 3D phantoms are used to diagnose the gravity of accidental exposure to radiation. In such cases, there may be from 10 to more than 1000 subjects to be diagnosed simultaneously. In all of these cases, computation accuracy depends on a single such representation. In this paper, we present EquiVox which is a tool composed of several distributed functions and enables to create, as quickly and as accurately as possible, 3D numerical phantoms that fit anyone, whatever the context. It is based on a multi-agent system. Agents are convenient for this kind of structure, they can interact together and they may have individual capacities. In EquiVox, the phantoms adaptation is a key phase based on artificial neural network (ANN) interpolations. Thus, ANNs must be trained regularly in order to take into account newly capitalized subjects and to increase interpolation accuracy. However, ANN training is a time-consuming process. Consequently, we have built Equivox to optimize this process. Thus, in this paper, we present our architecture, based on agents and ANN, and we put the stress on the adaptation module. We propose, next, some experimentations in order to show the efficiency of the EquiVox architecture.

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Caffo, Orazio, Viviana Frantellizzi, Fabio Monari, Luca Galli, Renato Patrizio Costa, Carmine Pinto, Marcello Tucci, et al. "Sequencing Life-Prolonging Agents in Castration-Resistant Prostate Cancer Patients: Comparison of Sequences With and Without 223Ra." Cancer Biotherapy and Radiopharmaceuticals 36, no. 5 (June 1, 2021): 391–96. http://dx.doi.org/10.1089/cbr.2020.4442.

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Singh, Sweta, Anjani K. Tiwari, Himanshu Ojha, Nitin Kumar, Bachcha Singh, and Anil K. Mishra. "SAR of Cu (II) Thiosemicarbazone Complexes as Hypoxic Imaging Agents: MM3 Analysis and Prediction of Biologic Properties." Cancer Biotherapy and Radiopharmaceuticals 25, no. 1 (February 2010): 117–21. http://dx.doi.org/10.1089/cbr.2009.0670.

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Nonnekens, Julie, Kristell L. S. Chatalic, Janneke D. M. Molkenboer-Kuenen, Cecile E. M. T. Beerens, Frank Bruchertseifer, Alfred Morgenstern, Joke Veldhoven-Zweistra, et al. "213Bi-Labeled Prostate-Specific Membrane Antigen-Targeting Agents Induce DNA Double-Strand Breaks in Prostate Cancer Xenografts." Cancer Biotherapy and Radiopharmaceuticals 32, no. 2 (March 2017): 67–73. http://dx.doi.org/10.1089/cbr.2016.2155.

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Nugroho, Soewignjo Agus, Ferry Fatnanta, and Muhammad Faizal Alridho. "EFFECT OF ADDING WOOD POWDER ASH ON CBR VALUE IN STABILIZED HIGH PLASTICITY CLAY CEMENT AND LIME." astonjadro 10, no. 2 (October 17, 2021): 301. http://dx.doi.org/10.32832/astonjadro.v10i2.5235.

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<p>Cement and lime are widely used as stabilizing agents for soft clays. Some pozzolanic materials have also been used as additives such as asphalt, geosta, fly ash (geopolymer), base ash, salt. Industrial waste such as rice husk ash, coal burning ash (geopolymer) is also used as an alternative for stabilization materials. This research aims to study the effect of sawdust ash, as wood waste, to replace cement and lime on the stabilization of high plasticity clay. The effectiveness of sawdust ash, in this study, was evaluated from the CBR value. The test samples were also reviewed under conditions with and without immersion and with and without curing. Based on the test results, lime is very effective as an additive because it increases the CBR value of more than 100 at a level of 10%. Wood husk ash also increases the CBR value by 100%. The use of cement, lime and wood husk ash requires curing time so that there is a strong bond between the clay and additives. The use of additives without curing did not increase the CBR value. In the stabilization of clay with 10% lime, replacement of lime with wood husk ash by 4%-6%, can be used as a road sub-grade with good quality.</p>

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Meyer, Larissa A., Brian M. Slomovitz, Bojana Djordjevic, Shannon N. Westin, David A. Iglesias, Mark F. Munsell, Yunyun Jiang, et al. "The Search Continues: Looking for Predictive Biomarkers for Response to Mammalian Target of Rapamycin Inhibition in Endometrial Cancer." International Journal of Gynecologic Cancer 24, no. 4 (May 2014): 713–17. http://dx.doi.org/10.1097/igc.0000000000000118.

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ObjectivePI3K/mammalian target of rapamycin (mTOR) pathway aberrations occur in 40% to 80% of endometrial cancer. Prior studies suggest KRAS mutations are associated with resistance to mTOR inhibitors in solid tumors. The objective of this study was to determine if biomarker expression in the PI3K/mTOR pathway or KRAS mutations would predict response to therapy with everolimus, an mTOR inhibitor.MethodsSpecimens from a phase II study of everolimus in recurrent endometrioid endometrial cancer were utilized. The primary end point was clinical benefit rate (CBR: objective response and nonprogression at 20 weeks). Correlative studies evaluating PTEN expression and phospho-S6 ribosomal protein (pS6rp) status by immunohistochemistry and KRAS mutational analysis were performed.ResultsSix of 28 evaluable patients achieved prolonged stable disease (SD) at 20 weeks (CBR, 21%). Loss of PTEN expression did not predict CBR (P = 0.62) with a positive predictive value (PPV) of 0.13. Five (83%) of 6 patients with SD maintained PTEN expression. Neither pS6rp expression (P = 0.65) nor KRAS mutation (P = 0.99) predicted CBR; the PPV was 0.14 for each. Eighty percent (4/5) of those with SD were KRAS wild type. Combined analysis of pS6rp expression and KRAS mutation provided 100% PPV (95% confidence interval, 39.6%–100%), suggesting no chance of CBR for these individuals with 100% specificity (95% confidence interval, 46.3%–100%).ConclusionsS6rp phosphorylation, loss of PTEN expression, and presence of KRAS mutations alone did not correlate with CBR. However, positive pS6rp staining combined with KRAS mutation performed with 100% PPV and specificity to predict nonresponse. Identifying patients who will not benefit from mTOR inhibitors can direct therapy and reduce exposure to agents that add toxicity without clinical benefit.

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Muzzammil, Tassawwar, Malcolm J. Moore, and James R. Ballinger. "In Vitro Comparison of Sestamibi, Tetrofosmin, and Furifosmin as Agents for Functional Imaging of Multidrug Resistance in Tumors." Cancer Biotherapy and Radiopharmaceuticals 15, no. 4 (August 2000): 339–46. http://dx.doi.org/10.1089/cbr.2000.15.339.

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Lee, Jii Bum, Hyung Soon Park, Su Jin Choi, Seong Gu Heo, Ho Jung An, Hye Ryun Kim, Min Hee Hong, et al. "Plasma tumor mutation burden is associated with clinical benefit in patients with non-small cell lung cancer treated with anti-programmed death-1 monotherapy." Therapeutic Advances in Medical Oncology 14 (January 2022): 175883592211417. http://dx.doi.org/10.1177/17588359221141761.

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Background: The clinical utility of plasma tumor mutational burden (pTMB) requires further validation. Herein, the pTMB and genetic alterations were investigated as predictive biomarkers for anti-PD-1 monotherapy outcome in metastatic non-small cell lung cancer (NSCLC). Methods: The GuardantOMNI panel (Guardant Health) was used to identify pTMB and genetic alterations. Data from 99 patients with metastatic NSCLC treated with pembrolizumab or nivolumab in first-, second-, or third-line settings between June 2016 and December 2020 were collected. Associations between pTMB and clinical benefit rate (CBR, stable disease ⩾6 months or partial response), progression-free survival (PFS), and overall survival (OS) were assessed. Results: Median pTMB in 84 patients was 10.8 mutations/megabase (mut/Mb). Histological analyses revealed that 61 and 36% of the patients had adenocarcinomas and squamous NSCLC, respectively. Most patients were treated with nivolumab (74%) and most anti-PD-1 agents were administered as second-line treatment (70%). The median follow-up duration was of 10.9 months (range, 0.2–40.7). Patients with high pTMB (⩾19 mut/Mb) had a higher CBR (69%) compared with low pTMB patients (33%; p = 0.01). ARID1A ( p = 0.007) and either ERBB2 or KIT mutations ( p = 0.012) were positive and negative determinants, respectively, for clinical benefit. Multivariate analysis further showed that high pTMB was an independent predictive biomarker for both PFS [hazard ratio (HR) = 0.44, 95% confidence interval (CI): 0.22–0.88, p = 0.02] and OS (HR = 0.37, 95% CI: 0.18–0.76, p = 0.007). Conclusion: High pTMB (⩾19 mut/Mb) is significantly associated with CBR in patients with NSCLC treated with anti-PD-1 agents.

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Iftikhar, Ahmad, Hamza Hassan, Nimra Iftikhar, Adeela Mushtaq, Atif Sohail, Nathaniel Rosko, Rajshekhar Chakraborty, et al. "Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development." Antibodies 8, no. 2 (May 24, 2019): 34. http://dx.doi.org/10.3390/antib8020034.

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Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively. Conclusions: Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted.

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Schepetkin, Igor. "Immune Response to Haptenized Tumor Antigen as Possible Mechanism of Anticancer Action of Hypoxic Bioreductive Agents at Low Doses." Cancer Biotherapy and Radiopharmaceuticals 14, no. 4 (August 1999): 291–96. http://dx.doi.org/10.1089/cbr.1999.14.291.

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Kotts, C. E., F. M. Su, C. Leddy, T. Dodd, S. Scates, M. R. Shalaby, C. M. Wirth, et al. "186Re-Labeled Antibodies to p185HER2as HER2-Targeted Radioimmunopharmaceutical Agents: Comparison of Physical and Biological Characteristics with125I and131I-Labeled Counterparts." Cancer Biotherapy and Radiopharmaceuticals 11, no. 2 (April 1996): 133–44. http://dx.doi.org/10.1089/cbr.1996.11.133.

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González, Carolina, Juan Carlos Burguillo, Martín Llamas, and Rosalía Laza. "Designing Intelligent Tutoring Systems: A Personalization Strategy using Case-Based Reasoning and Multi-Agent Systems." ADCAIJ: Advances in Distributed Computing and Artificial Intelligence Journal 2, no. 1 (May 7, 2013): 41–54. http://dx.doi.org/10.14201/adcaij2013244154.

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Intelligent Tutoring Systems (ITSs) are educational systems that use artificial intelligence techniques for representing the knowledge. ITSs design is often criticized for being a complex and challenging process. In this article, we propose a framework for the ITSs design using Case Based Reasoning (CBR) and Multiagent systems (MAS). The major advantage of using CBR is to allow the intelligent system to propose smart and quick solutions to problems, even in complex domains, avoiding the time necessary to derive those solutions from scratch. The use of intelligent agents and MAS architectures supports the retrieval of similar students models and the adaptation of teaching strategies according to the student profile. We describe deeply how the combination of both technologies helps to simplify the design of new ITSs and personalize the e-learning process for each student

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Okarvi, Subhani M., and Ibrahim A. Jammaz. "Preparation and In Vitro and In Vivo Evaluation of Technetium-99m-Labeled Folate and Methotrexate Conjugates as Tumor Imaging Agents." Cancer Biotherapy and Radiopharmaceuticals 21, no. 1 (February 2006): 49–60. http://dx.doi.org/10.1089/cbr.2006.21.49.

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Vandenbulcke, Katia, Hubert Thierens, Filip De Vos, Jan Philippé, Fritz Offner, Ann Janssens, Christos Apostolidis, et al. "In VitroScreening for Synergism of High-Linear Energy Transfer213Bi-Radiotherapy with Other Therapeutic Agents for the Treatment of B-Cell Chronic Lymphocytic Leukemia." Cancer Biotherapy and Radiopharmaceuticals 21, no. 4 (August 2006): 364–72. http://dx.doi.org/10.1089/cbr.2006.21.364.

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Olugbenga Oludolapo Amu, Christopher Ehizemhen Igibah, Bamitale Dorcas Oluyemi-Ayibiowu, and Lucia Omolayo Agashua. "Effect of triaxial and CBR Scrutiny on mechanical strength and microstructure of kaolin clay powder mixed SSA geopolymer and its performance at various percentages." World Journal of Engineering and Technology Research 1, no. 1 (January 30, 2022): 011–20. http://dx.doi.org/10.53346/wjetr.2022.1.1.0024.

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The stabilization capability of kaolin clay powder (KCP), Ordinary Portland cement (OPC) and rice husk ash (RHA) was scrutinized using laboratory scrutiny. This was meant at assessing the effect of KCP, OPC and RHA on the stabilization of three lateritic soils for use as sub-base pavement layer materials. Three soils (Soil A, B and C) were improved with various percentages (via weight of dry soil) at 0, 2, 4, 6, 8 and 10% for all stabilizing agents and compacted via BSL (British Standard light) energy. Their impacts were assessed on the strength physiognomies such as UCS (unconfined compressive strength), OMC (optimum moisture content), and California bearing ratio (CBR), and MDD (maximum dry density tests based on ASTM (American Standard Testing Materials) codes. The result reveals that MDD improved with increase in the quantities of all the additive (SSA, KCP and geopolymer) content, while OMC for KCP reduces from 18.65% at 0% to 14.02%. Both SSA and geopolymer increase from 18.65% at 0% to 18.86% and 22.20% at 10%. Similarly it displays highest CBR of the soil from 10.88% at 0% to 12.84%, 112.95% and 144.45% for (SSA, KCP and geopolymer, this specify that lateritic soil treated with 2% stabilizer yielded CBR values of more than 405%.

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Bamitale Dorcas Oluyemi-Ayibiowu, Lucia Omolayo Agashua, Ehizemhen Christopher Igibah, Olugbenga Oludolapo Amu, Adedapo Oluwaseun Adetayo, Olumuyiwa Samson Aderinola, and Tochukwu Ernest Ugochukwu. "Impact of sodium silicate with normal pH on mechanical strength of rice husk blend geopolymer and its performance at various percentages." World Journal of Advanced Science and Technology 1, no. 2 (June 30, 2022): 001–10. http://dx.doi.org/10.53346/wjast.2022.1.2.0027.

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The stabilization capability of kaolin clay powder (KCP), Ordinary Portland cement (OPC) and rice husk ash (RHA) was scrutinized using laboratory scrutiny. This was meant at assessing the effect of KCP, OPC and RHA on the stabilization of three lateritic soils for use as sub-base pavement layer materials. Three soils (Soil A, B and C) were improved with various percentages (via weight of dry soil) at 0, 2, 4, 6, 8 and 10% for all stabilizing agents and compacted via BSL (British Standard light) energy. Their impacts were assessed on the strength physiognomies such as UCS (unconfined compressive strength), OMC (optimum moisture content), and California bearing ratio (CBR), and MDD (maximum dry density tests based on ASTM (American Standard Testing Materials) codes. The result reveals that MDD improved with increase in the quantities of all the additive (SSA, KCP and geopolymer) content, while OMC for KCP reduces from 18.65% at 0% to 14.02%. Both SSA and geopolymer increase from 18.65% at 0% to 18.86% and 22.20% at 10%.Similarly, it displays highest CBR of the soil from 10.88% at 0% to 12.84%, 112.95% and 144.45% for (SSA, KCP and geopolymer, this specify that lateritic soil treated with 2% stabilizer yielded CBR values of more than 405%.

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Ma, Zhuo, Lifang Guo, Xiangli Cui, He Liu, and Lihong Liu. "Rh-endostatin Concomitant with Chemotherapy Versus Single Agent Chemotherapy for Treating Soft Tissue and Bone Sarcomas: A Systematic Review and Meta-Analysis." Journal of Pharmacy & Pharmaceutical Sciences 21 (October 23, 2018): 386–97. http://dx.doi.org/10.18433/jpps30034.

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Objectives: Endostar (recombinant human endostatin (rh-endostatin)), a 20-kDa proteolytic fragment of collagen XVIII, was approved for the treatment of non–small cell lung cancer (NSCLC). Recently, several studies have evaluated the efficacy of rh-endostatin combined with chemotherapy in the treatment of bone and soft tissue sarcomas. Here, we conducted a systematic review and meta-analysis to assess available evidence. Methods: Pubmed, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, WanFang) were systematically searched till May 20, 2018. Randomized controlled trials (RCTs) and cohort studies which compared the outcomes of rh-endostatin combined with chemotherapy versus chemotherapy alone for treating bone sarcomas or soft tissue sarcomas were included. The primary outcome was overall survival rate (OSR). Secondary outcomes included objectiveremissionrate(ORR), clinical benefit rate (CBR), disease control rate (DCR), distant metastasis rate (DMR) and adverse effects (AEs). The methodological quality of the included studies was evaluated. Data analysis was performed by Revman 5.3 software. Results: 9 studies comprising 839 patients were included. The pooled results indicated that, compared with chemotherapeutic agents alone, rh-endostatin combined group had a significant benefit in 1-year and 2-year OSR. However, there were no difference between 5-year OSR. OR, CBR and DMR were higher in rh-endostatin combined group. No significant difference was observed in the incidence of AEs. Conclusions: Rh-endostatin combined chemotherapeutic agents significantly improved clinical efficacy compared with chemotherapeutic agents alone in treating bone and soft tissue sarcomas. Moreover, combination of rh-endostatin with chemotherapy didn’t increase the incidence of AEs. But more high quality RCTs with large sample size should be done in the future to confirm the conclusion.

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Forero, Andres, Ruby F. Meredith, M. B. Khazaeli, Sui Shen, William E. Grizzle, Delicia Carey, Elizabeth Busby, Albert F. LoBuglio, and Francisco Robert. "Phase I Study of 90Y-CC49 Monoclonal Antibody Therapy in Patients with Advanced Non-Small Cell Lung Cancer: Effect of Chelating Agents and Paclitaxel Co-Administration." Cancer Biotherapy and Radiopharmaceuticals 20, no. 5 (October 2005): 467–78. http://dx.doi.org/10.1089/cbr.2005.20.467.

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xie, ping, Siqi Chen, Mathew Cowan, Hao Huang, Horacio Cardenas, Masha Kocherginsky, Daniela Matei, and Bin Zhang. "Immune characterization in platinum resistant ovarian cancer patients treated with pembrolizumab and guadecitabine." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 119.15. http://dx.doi.org/10.4049/jimmunol.208.supp.119.15.

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Abstract Immune checkpoint inhibitors (ICI) have limited activity in ovarian cancer (OC). Accumulating preclinical and early clinical results support that interventions targeting the epigenome could elicit an inflamed tumor milieu to augment ICI. Here we explore the clinical and biological activity of guadecitabine, a second generation Hypomethylating agents (HMA), given in low dose as a priming strategy before pembrolizumab, a humanized anti-PD1 antibody in a clinical trial for patients with recurrent, platinum-resistant OC. Among 35 evaluable patients, there were 3 partial responses (8.6%) and 8 (22.9%) patients with stable disease, resulting in clinical benefit rate (CBR) of 31.4%. Median duration of clinical benefit was 6.8 months. High dimensional immune profiling of PBMCs showed higher frequency of naive and/or central memory CD4+ T cells and of classical monocytes in patients with durable CBR. Higher baseline density of CD8+ T and CD20+ B cells and presence of tertiary lymphoid structures in tumors were associated with durable CBR. The molecular features such as expression levels of PD-L1 or A2AR linked to therapeutic benefit for resistant OC. Our study provides an in-depth view of the immune milieu of platinum resistant OC and of the effects of the combination of HMAs and pembrolizumab on the interactions between immune cell populations and tumor cells. Supported by USAMRMC/CDMRP (W81XWH170141)

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Byrd, Kenneth, Panduka Nagahawatte, Michael Gary Martin, Matthew K. Stein, Kruti Patel, Lee Steven Schwartzberg, and Ari M. Vanderwalde. "Correlation between PD-L1 expression level and clinical benefit in 204 patients across malignancies at a single institution." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e14573-e14573. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14573.

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e14573 Background: The utility of PD-L1 expression levels in predicting response to anti-PD-1 agents in many malignancies is uncertain. In this study, we describe outcomes of patients treated with anti-PD-1 agents by PD-L1 expression level. Methods: Molecular profiling of tumors in patients with newly diagnosed metastatic cancer was performed at West Cancer Center starting late 2014. Most profiling was performed by Caris, which in addition to NGS also reports PD-L1 expression (IHC, reported as percent expressed). Patients were included in this retrospective analysis if they were treated with an anti-PD-1 antibody and had available results from PD-L1 testing between 11/2014 and 11/2016. Time to treatment failure (TTF) was defined as time from first dose to documented progression, intolerance or death. Those without treatment failure were censored at the date of last contact. Pending formal retrospective RECIST review, clinical benefit rate (CBR) is reported. Results: 204 patients with reported PD-L1 expression started treatment with anti-PD-1 agents. Of these, 125 had non-small cell lung cancer, 31 had melanoma, 12 had renal cell carcinoma, and the remainder had other malignancies. 110 patients (54%) had PD-L1 expression level of 0%, 22 patients (11%) between 1-4%, 37 patients (18%) between 5-49%, and 35 patients (17%) >50%. Median TTF and CBR by PD-L1 overall and by malignancy are shown in the table below. Conclusions: Higher PD-L1 expression does appear to be associated with increased clinical benefit rate and time to treatment failure, though the highest levels of PD-L1 did not follow this pattern. Based on these surrogate endpoints, there appears to be substantial benefit with PD-1 inhibitor treatment even with 0% PD-L1 expression. Objective response rate will be presented. [Table: see text]

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Tripathi, AN, Rajesh Kumar Singh, and SK Tiwari. "Evaluation of bio-control agents and new fungicides to control Pythium damping off in nursery of solanaceous vegetable crops." Vegetable Science 49, no. 01 (June 30, 2022): 91–95. http://dx.doi.org/10.61180/vegsci.2022.v49.i1.14.

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Nursery of solanaceous vegetable crops severely infected by damping - off. Commercial cultivation of solanaceous vegetables are depends on healthy and disease free seedlings under nursery condition in fields. Seed treatments are most cost effective and commonly used delivery system for bioagents and fungicides. Nine modules comprises three talc based fungal [Trichoderma viride- 1 (IIVR–BATF-39-1), T. viride-2 (IIVR-BATF-43-1), Trichoderma harzianum - Kalyanpur)], two bacterial (Bacillus subtilis (IIVR-BS2, Pseudomonas fluorescens -Kalyanpur) formulations and four fungicides (carbendazim 12% + mancozeb 63% WP, pencycuron 250 SC, fosetyl-Al 80% WP, fenamidone 10% + mancozeb 50% (WP) were evaluated under nursery of tomato, brinjal and chilli in kharif season during 2016-2018. Among tested bio-formulations of bio-agents Bacillus subtilis (IIVR-BS2 ) was found effective for highest germination percentage in tomato (84.77) and brinjal (66.81) and lowest incidence of damping off 15.22% and 33.18%, repectively whereas cost benefit ratio (CBR) 1: 79.98 (tomato var. Kashi Aman) and 1: 36.69 (brinjal var Kashi Taru) were recorded. However, among all tested modules, a fungicide carbendazim 12% WP + mancozeb 63% WP was found most effective in chilli for highest germination percentage (86.58), vigour index (479.52) and lowest incidence of damping off (13.30) with cost benefit ratio (CBR) 1: 90.79. Hence, use of bio-agent Bacillus subtilis (IIVR-BS2) 3.92×1011 cfu/g in tomato and brinjal; however, combiproduct of carbendazim (12%) and mancozeb (63%) in chilli may be recommended for management of damping off in nursery.

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Guleria, Mohini, Tapas Das, Jeyachitra Amirdhanayagam, Haladhar D. Sarma, and Ashutosh Dash. "Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on Pharmacokinetics and Tumor Uptake in a Mouse Model." Cancer Biotherapy and Radiopharmaceuticals 33, no. 1 (February 2018): 8–16. http://dx.doi.org/10.1089/cbr.2017.2337.

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Harianto, Tri. "Performance of Subbase Layer with Geogrid Reinforcement and Zeolite-Waterglass Stabilization." Civil Engineering Journal 8, no. 2 (February 1, 2022): 251–62. http://dx.doi.org/10.28991/cej-2022-08-02-05.

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Some laterite soil is an inferior material for engineering applications such as road and highway pavement, dam construction and filling material. Laterite soil stabilization is required to increase its strength for field application purposes. The potential use of zeolite and waterglass as stabilizing agents is their pozzolanic properties. This study aims to analyze the strength and bearing capacity of laterite soil stabilized by waterglass-activated zeolite and reinforced with geogrid. The soil sample was prepared with a zeolite percentage of 4, 8, 12, 16 and 20%, and waterglass as much as 2, 4 and 6% with curing times of 0, 7, 14 and 28 days. Furthermore, the physical model test was carried out in the container with the optimum composition obtained from the compressive strength (UCS) and California bearing test (CBR) test. The stabilized subbase layer with geogrid reinforcement was placed on a subgrade layer with a substandard CBR value. The results showed that the compressive strength (UCS) of stabilized soil with a curing time of 7 days was found significantly increased. The CBR value also increased with the content of additive and curing time compared to the untreated soil. The physical model test results showed that the performance of stabilized laterite soil with additives and reinforced by geogrid (ZW-geogrid) as a subbase layer provides more optimal performance in carrying the load compared to the sand-gravel mixtures material. Doi: 10.28991/CEJ-2022-08-02-05 Full Text: PDF

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Rabbanifar, Saeed, Thi Thuy Minh Nguyen, Qin Qian, Nicholas A. Brake, Kyle Kibodeaux, Harold E. Crochet, Soheil Oruji, et al. "Reusing Dredged Material through Stabilization with So-Called Bio-Enzyme Products." Buildings 13, no. 10 (October 17, 2023): 2618. http://dx.doi.org/10.3390/buildings13102618.

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Sediments are dredged from waterways to maintain maritime activities and prevent floods. Exorbitant amounts of money are budgeted for the removal of dredged material (DM) and its disposal in landfills. We investigated the potential for reuse of DM as a road construction material using so-called bio-enzyme products as stabilizing agents. To improve the mechanical properties of DM, such as compressive strength, compressibility, Atterberg limits and the California bearing ratio (CBR), mixtures of DM were tested with two different amounts of a commercially available bio-enzyme product, which yielded enzymatically stabilized dredged material (ESDM). Unconfined compressive strength (UCS), compaction and Atterberg limits were measured in accordance with ASTM specifications on all samples. Data show that the addition of bio-enzymes resulted in increases in UCS but did not affect the optimum moisture content (OMC), maximum dry unit weight or Atterberg limits of the DM. A comparative field study was carried out to evaluate the CBR of the CH subgrade before and after treatments with the bio-enzyme product and with lime as a traditional stabilizing agent. The results of the field study supported the laboratory findings. Based on these data and results from the literature, models predicting the effect of bio-enzyme treatments on the value of CBR and of UCS were developed statistically. These models also underlined the importance of the clay fraction and PI values for the improvement of the engineering properties of soil using bio-enzyme additives.

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Zhu, Anjie, Peng Yuan, Jiayu Wang, Fei Ma, Yang Luo, Ying Fan, Qing LI, Pin Zhang, and Binghe Xu. "A real-world retrospective study of apatinib plus chemotherapy in metastatic breast cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e12507-e12507. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e12507.

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e12507 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical outcome in advanced breast cancer(ABC). Apatinib is an orally administered tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), which exhibited objective efficacy in metastatic breast cancer(MBC). We performed a retrospective observational analysis to evaluate the efficacy and safety of apatinib plus chemotherapy in the real-world practice of patients with MBC. Methods: Patients who have failed at least one prior chemotherapy regimen for metastatic disease were included in this study. The primary endpoint was progression free survival(PFS). Secondary end points included objective response rate(ORR), clinical benefit rate(CBR), overall survival(OS) and safety. Data analysis included association between clinicopathological characteristics or treatment choice and PFS. Results: Of the 23 patients analyzed, 14(60.9%) received plant-derived anticancer agents combined therapy and 9(39.1%) combined with non-plant-derived agents. Objective response rate(ORR) was 34.7% and clinical benefit rate(CBR) reached 52.2% on last tumor assessment. With a median follow-up of 9.0 months, the estimated median PFS and OS were 5.4 months (95%CI 3.5-7.3) and 8.2 months (95%CI 4.7-11.7), respectively. Toxicities were tolerable or could be clinically managed.The most frequently observed adverse events (AEs) of all grade were hypertension, myelosuppression, hand-foot syndrome, proteinuria, fatigue and gastrointestinal reaction. The most common grade 3/4 treatment-related AEs were myelosuppression(39.1%) and gastrointestinal reaction(17.4%). Conclusions: In this retrospective observational study, combination of apatinib with chemotherapy demonstrated clinically relevant efficacy and tolerability in metastatic breast cancer.

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Radwan, Mohammed K. H., Foo Wei Lee, Yoke Bee Woon, Ming Kun Yew, Kim Hung Mo, and Soon Han Wai. "A Study of the Strength Performance of Peat Soil: A Modified Cement-Based Stabilization Agent Using Fly Ash and Polypropylene Fiber." Polymers 13, no. 23 (November 23, 2021): 4059. http://dx.doi.org/10.3390/polym13234059.

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The use of cement as a soil stabilization agent is one of the common solutions to enhancing the engineering properties of soil. However, the impact and cost of using cement have raised environmental concerns, generating much interest in the search for alternative materials to reduce the use of cement as a stabilizing agent in soil treatment. This study looked into limiting cement content in peat soil stabilization by using fly ash waste and polypropylene fiber (PPF). It focused on soil mechanical mediation for stabilization of peat with fly ash cement and PPF cement by comparing the mechanical properties, using unconfined compressive strength (UCS) and California bearing ratio (CBR) tests. The control (untreated) peat specimen and specimens with either fly ash (10%, 20% and 30%) and PPF (0.1%, 0.15% and 0.2%) were studied. Test results showed that 30% of fly ash and cement content displays the highest UCS and CBR values and gives the most reliable compressibility properties. On the other hand, UCS and CBR test results indicate optimum values of PPF–cement stabilizing agent content in the specimen of 0.15% PPF and 30% cement. Selected specimens were analyzed using scanning electron microscopy (SEM), and PPF threads were found to be well surrounded by cement-stabilized peat matrices. It was also observed that the specimen with 30% fly ash generated more hydration products when compared to the specimen with 100% cement content. It is concluded that the use of fly ash cement and PPF cement as stabilizing agents to limit the cement usage in peat soil treatment is potentially viable.

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Zhao, Yannan, Ning Xie, Wei Li, Wenyan Chen, Zheng Lv, Yabing Zheng, Tao Sun, et al. "Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: A multicenter retrospective study." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e13057-e13057. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e13057.

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e13057 Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxane. The aim of this study was to evaluate the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Methods: A total of 272 consecutive MBC patients who were treated with eribulin from November 2019 to October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 3.9 months (95% confidence interval [CI] 3.3–4.3); however, the OS data were immature. The ORR was 16.2%, and the CBR was 21.7%. A total of 51.8% of patients received eribulin monotherapy, and 48.2% of patients were treated with eribulin combine with targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination regimen with bevacizumab were significant in Cox multivariate analysis (p=0.048, p=0.039, and p=0.045, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusions: This is the first cohort of eribulin real-world data base on retrieval currently after eribulin launched in China. Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agents. Eribulin monotherapy or combine with other agents is alternative for the heavily pretreated patients with MBC. [Table: see text]

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Wiberg, Nils, Ch M. M. Finger, T. Passler, S. Wagner, and K. Polborn. "Zur Erzeugung von Silaethenen des Typus R2Si=CH(SiR3 ) und R2Si=CH2 durch thermische Salzeliminierung sowie zur Kenntnis von R2Si=CH(SitBu3) (R = Me, tBu ) / On the Generation of Silaethenes of the Types R2Si=CH(SiR3) and R2Si=CH2 by Thermal Salt Elimination and on the Knowledge of R2Si=CH(SitBu3) (R = Me, tBu)." Zeitschrift für Naturforschung B 51, no. 12 (December 1, 1996): 1744–60. http://dx.doi.org/10.1515/znb-1996-1212.

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The generation of silaethenes Me2Si=CH(SiMe3) (1), Me2Si=CH(SitBu3) (2), tBuMeSi=CH(SitBu3) (3), and tBu2Si=CH2 (4) from metal organyls >SiX-CM< (X = Br, F; M = Na, Li) by elimination of MX is investigated. The metal organyls are prepared from >SiX-CBr< and RM (R = tBu3Si, nBu, Ph) by Br/M exchange (for preparation of >SiX-CBr< cf. Scheme 1). Only the sterically overcrowded silaethenes 2 and 3. generated from Me2SiF-CHNa(SitBu3) and tBuMeSiF-CHNa(SitBu3), have been identified by trapping with isobutene and dimethylbutadiene under formation of ene and Diels-Alder adducts. Analogous products are not found from Me2SiBr-CHNa(SiMe3) and tBu2-SiBr-CH2-Li. In the absence of trapping agents, compounds 1, 2, and 3 form cyclodimers. A reaction intermediate of the formation of 1 × 1 has been isolated and the structures of 2 × 2 and 3 × 3 have been solved by X-ray analysis. No dimer is observed for 4. In this case compounds are formed which may be interpreted as insertion products of 4 into the CLi bond of the precursor.

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van Rhee, Frits, Luis Fayad, Peter Voorhees, Richard Furman, Sagar Lonial, Hossein Borghaei, Lubomir Sokol, et al. "Siltuximab, a Novel Anti–Interleukin-6 Monoclonal Antibody, for Castleman's Disease." Journal of Clinical Oncology 28, no. 23 (August 10, 2010): 3701–8. http://dx.doi.org/10.1200/jco.2009.27.2377.

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Purpose Interleukin-6 (IL-6) has emerged as a key factor in the pathogenesis of the atypical lymphoproliferative disorder Castleman's disease (CD). Siltuximab is a new anti–IL-6, chimeric monoclonal antibody with potential therapeutic benefit in patients with CD. Methods We report interim results from an open-label, dose-finding, seven-cohort, phase I study in which patients with symptomatic, multicentric or unresectable, unicentric CD received siltuximab at 1-, 2-, or 3-week intervals. The main efficacy end point of clinical benefit response (CBR) was defined as a composite of clinical and laboratory measures relevant to the management of CD. In addition, radiologic response was independently assessed by using modified Cheson criteria. Results Eighteen (78%) of 23 patients (95% CI, 56% to 93%) achieved CBR, and 12 patients (52%) demonstrated objective tumor response. All 11 patients (95% CI, 72% to 100%) treated with the highest dose of 12 mg/kg achieved CBR, and eight patients (73%) achieved objective tumor response. Overall objective-response duration ranged from 44 to ≥ 889 days, and one patient had complete response for ≥ 318 days. Hemoglobin increased markedly in 19 patients (median increase, 2.1 g/dL; range, 0.2 to 4.7 g/dL) in the absence of transfusion or erythropoiesis-stimulating agents. No dose-limiting toxicity was reported, and only three patients had grade 3 or higher adverse events after a median exposure of 331 days (range, 1 to 1,148 days). Conclusion These interim results strongly suggest that siltuximab is an effective treatment with favorable safety for the management of CD. An additional study is planned to fully evaluate safety and efficacy at the recommended dose of 12 mg/kg every 3 weeks.

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Zhao, Yannan, Ning Xie, Wei Li, Wenyan Chen, Zheng Lv, Yabing Zheng, Tao Sun, et al. "Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592110302. http://dx.doi.org/10.1177/17588359211030210.

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Background: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. Patients and Methods: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6–4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis ( p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. Conclusion: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

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Sandeep, K. Venkata Surya, and Ch Sivanarayana. "An Experimental Study on Stabilization of Expansive Soil by Copper Slag." International Journal for Research in Applied Science and Engineering Technology 10, no. 11 (November 30, 2022): 431–42. http://dx.doi.org/10.22214/ijraset.2022.47340.

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Abstract: Stability of any structure depends on strength properties of underground soil on which it is constructed. Structures basically transfer all the loads come on itself directly to the ground. If the underlying soil is not stable enough to support transferred loads then various types of failure occur such as settlement of the structure, cracks and so on. To solve this issue, soil improvement is necessary because it not only lowers the construction cost but also cuts the risk of any damage of structure later on. Numerous improvement methods can be adopted to make ordinary soil stable enough to support the structural loads. In this research work a number of tests may conduct using both ordinary soil and stabilised soil. The stabilising agents are using in this study is Copper Powder. The varying percentage of 5%, 10%, 15%, 20% and 25% added to the expansive soil. It binds the soil particles together and helps in reduction of rapid change in volumetric properties. The tests may conduct on un-stabilised and stabilised expansive soil is CBR, UCS and tri-axial test.The test may conducted on untreated and treated expansive soil i.e. index properties (liquid limit, plastic limit), compaction test, California bearing ratio (CBR), unconfined compressive test (UCS), Triaxial test

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Colombo, N., S. McMeekin, P. Schwartz, J. Kostka, C. Sessa, P. Gehrig, R. Holloway, P. Braly, D. Matei, and M. Einstein. "A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 5516. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.5516.

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5516 Background: There are few effective therapies for women with advanced or recurrent endometrial cancer. Targeted therapies such as AP23573, a novel mTOR inhibitor, may result in clinical benefit with fewer side effects. Preliminary results of a trial of single agent AP23573 in patients with progressive endometrial cancer who may have had up to 2 prior regimens of cytotoxic chemotherapy are reported. Methods: The trial is an open-label, Simon 2-stage, single-arm study enrolling patients who have advanced endometrial cancer with documented progression in the 3 months prior to entry. Patients receive 12.5mg AP23573 QDx5 as a 30-min. intravenous infusion every other week for 28-day cycles. The primary efficacy endpoint is Clinical Benefit Response (CBR), defined as a complete or partial response or prolonged stable disease (= 16 weeks) by modified RECIST guidelines. Results: Seven of the first 19 patients achieved CBR, allowing expansion to the second stage. Enrollment is now complete (45 patients). Demographic data are available for 35 (median 66 yrs.; range 46–89) patients who received treatment: 23 adenocarcinomas, 5 carcinosarcomas, 6 papillary serous carcinomas (UPSC) and 1 clear cell carcinoma. Thirty-four patients had prior chemotherapy including doxorubicin, taxanes or platinum agents. Fourteen of the 26 patients with available history had prior pelvic radiotherapy. Nine of 27 (33%) patients evaluable for response had CBRs, including 2 partial responses (PRs). One CBR had UPSC, the remaining patients, including the PRs, had adenocarcinomas. Seven of the patients achieving CBR are still on treatment. Eighteen of the 27 patients discontinued treatment before 4 cycles because of progressive disease (14), consent withdrawal (1) or unrelated adverse events (3). Adverse event data are available for 27 patients. The most common adverse events are fatigue, anemia (33% each), mouth sores and nausea/vomiting (30% each). There have been 16 grade 3/ 4 treatment related adverse events (2 hyperglycemia, 14 separate events similar to those reported in other AP23573 trials). Conclusions: AP23573 shows encouraging single-agent activity in pretreated patients with advanced, progressive endometrial cancer and is well tolerated. No significant financial relationships to disclose.

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Singh, Jasmeet Chadha, Stacy Stein, Matthew Volm, Julia Anne Smith, Sylvia Adams, Marlene Meyers, James L. Speyer, et al. "RAD001-carboplatin combination in triple-negative metastatic breast cancer (TNMBC): A phase II trial." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 1042. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.1042.

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1042 Background: Triple negative breast cancer cells often show genetic instability and inability to repair DNA damage rendering them sensitive to platinum agents. Rapamycin enhances platinum- induced apoptosis in breast cancer cell lines. We sought to explore the activity/toxicity of the of carboplatin with RAD001 in TNMBC. Methods: The primary objective of this study was to estimate clinical benefit rate/CBR (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting >6 months) and the toxicity of this combination in women with TNMBC who have had 0-3 prior chemoregimens for MBC. 25 subjects were recruited. This design had > 80% power to test the null hypothesis that the CBR is ≤10% vs. alternative hypothesis that CBR is ≥ 30% (≥6 would need to achieve a clinical benefit). Prior Carboplatin was allowed. Women with treated brain metastasis were eligible. Originally, Carboplatin AUC 6 was administered q3 weeks with daily 5mg of RAD001 with a 3 patient run-in, then 10 mg daily. Due to excessive thrombocytopenia, the dose of Carboplatin was first amended to AUC 5 and then to AUC 4 with 5 mg of RAD001 (no escalation to 10 mg). Results: All 25 patients have been recruited. Median age is 58.There have been 1 CR, 6 PR’s, 2 SD's lasting >6 months and 6 PD’s. 3 patients were not evaluable. One SD achieved in a patient progressing on single agent Carboplatin. The estimated CBR is 36% (95% C.I.: 17%-55%). Median PFS is 3.3 months (95% C.I.: 2.4-7.7 months) from start of treatment. 7 patients (28%) had grade 3 or 4 thrombocytopenia and 3 (12%) had grade 3 neutropenia (no bleeding/ febrile neutropenia). Since amendment of Carboplatin to AUC 4 the regimen has been very well tolerated with only 11% grade 3 hemetoxicity. The grade 3 non-heme toxicities included nausea/ vomiting (n=1), mucositis (n=1) and dehydration (n=1). Grade 3 insomnia (n=1) and dyspnea (n=1) were thought to be unrelated to the treatment (no grade 3 fatigue/ interstitial lung disease). Conclusions: The study has achieved the primary end point of demonstrating clinical benefit in TNMBC. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. Clinical trial information: NCT01127763.

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Kulcsár, Gyula. "Experimental Evidence for Killing the Resistant Cells and Raising the Efficacy and Decreasing the Toxicity of Cytostatics and Irradiation by Mixtures of the Agents of the Passive Antitumor Defense System in the Case of Various Tumor and Normal Cell Lines in Vitro." Cancer Biotherapy and Radiopharmaceuticals 24, no. 1 (February 2009): 67–80. http://dx.doi.org/10.1089/cbr.2008.0561.

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Soto, Juan José, Carlos Erasun Lecuona, Sandra Llop Serna, Nuria Mulet Margalef, Agostina Stradella, Rafael Villanueva, Mariona Calvo Campos, et al. "Outcomes of patients (pts) treated with novel immunotherapy (IT) agents in phase 1 clinical trials (Ph1-CT) at early lines for advanced disease." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 2581. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.2581.

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2581 Background: The overall survival (OS) benefit observed with immune checkpoint inhibitors led to their approval in many tumor types. Given the large number of IT compounds in early clinical development, many pts are offered IT within Ph1-CT even before having exhausted standard of care (SOC) therapies. We assessed outcomes of pts receiving novel IT treatments within Ph1-CT at the Phase 1 Unit of Catalan Institute of Oncology (ICO), Barcelona, Spain. Methods: We retrospectively reviewed a correlative series of pts with advanced/metastatic solid tumors treated with IT within Ph1-CT at ICO from January 2018 to June 2021. Primary endpoint was to assess clinical outcomes measured by median progression-free survival (mPFS) and median OS (mOS) according to number of prior lines (PL) for recurrent/metastatic disease, grade 3-4 toxicity (G3-4 Tox) and age. Data on prior IT (yes vs no) and availability of alternative SOC were evaluated. Overall response rate (ORR) was assessed according to RECIST 1.1. Clinical benefit rate (CBR) was defined as complete/partial response + stable disease for ≥6 months (m). PFS/OS were calculated by Kaplan-Meier method. Log-rank test was used for comparisons. Median PFS of alternative SOC according to historical data was recorded by tumor type and line of treatment. Results: A total of 104 pts received IT within Ph1-CT: IT monotherapy = 39 (37.5%), IT combinations = 65 (62.5%) (IT+IT = 59 [90.8%], IT+targeted therapy = 6 [9.2%]). Median age was 54 y (42-77), 62.5% were men and all had ECOG 0-1. Four most frequent cancers were urothelial (19.2%), colorectal (15.3%), head & neck (12.5%) and glioblastoma (11.5%). Number of PL: 0 = 20 (19.2%) pts, 1 = 37 (35.6%) pts, ≥2 = 47 (45.2%) pts. Nine (8.6%) pts had received prior IT. G3-4 Tox rate for the overall population was 19.2% and for pts who had received prior IT was 33%. ORR was 11.5%; CBR was 24%. Overall mPFS and mOS were 2.7m and 8.6m, respectively. Pts with less PL had greater mPFS and mOS (p < 0.05) (Table). Pts with available alternative SOC had lower mPFS but similar mOS compared to historical SOC (2.6m vs 4.8m, 11.4m vs 11.8m, respectively). G3-4 Tox (yes vs no) and age ( < 70 vs ≥70) did not significantly impact on mOS or mPFS (p = 0.18 and p = 0.83, respectively). At end of Ph1-CT treatment, 47 (45.2%) pts worsened their ECOG status, 15 (14.4%) pts were enrolled in a subsequent trial and 22 (21.1%) pts received SOC. Conclusions: In our cohort of pts treated with novel IT within Ph1-CT, overall clinical outcomes were modest in terms of mPFS, mOS, and CBR. However, pts with less pre-treated tumors seem to achieve higher survival benefit from early treatment with IT within Ph1-CT, although this benefit remains unclear in pts with alternative SOC. [Table: see text]

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Vincent, Azunna Chukwuma, and Chiedozie F. Ikebude. "A Comparative Study on the Stabilization of Soft Soil Using Agricultural Wastes (Baggase Ash (BA) And Rice Husk Ash (RHA)." International Journal of Civil Engineering, Construction and Estate Management 11, no. 2 (February 15, 2023): 39–69. http://dx.doi.org/10.37745/ijcecem.14/vol11n23969.

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Soft soils are expansive soils, also referred to as tropical clay. Soft soil may cause instability to foundations thereby reducing their service life, this necessitates the adoption of a suitable soil stabilization method in order to improve the engineering properties of soft soils. This research work aims at comparing the strength properties of soft soil stabilized using two different agricultural wastes- Bagasse Ash (BA) and Rice Husk Ash (RHA). The studies were conducted to determine the properties of the natural and treated soft soils, the oxide composition of BA and RHA and the evaluation of the effect of BA and RHA (0, 2, 4, 6, 8, 10 and 12 % by dry weight of the soil) on the index and strength properties of soft soil, the determination of strength characteristics (proctor compaction , unconfined compressive strength (UCS), and California bearing ratio, (CBR) under soaked and unsoaked conditions) of soft soil with BA and RHA mixtures, the optimum blend of both BA and RHA needed for the stabilization of clay soil, the comparison of BA and RHA as stabilizing agents on the performance of clay soil. From the test results, it was observed of the natural moisture content of the clay soil was to be 18.02%, indicating that the soil material is a relatively high water holding material with very low porosity and specific gravities of 2.66. The maximum dry density (MDD) of BA treated soil increased with higher BA content to an optimum BA content lying between 8-10% of dry clay soil and MDD of RHA treated soil continuously decreased with addition of RHA to the clay soil. OMC of BA and RHA treated soils continuously increase, the BA treated clay soil increase with increase in BA content with a possible percentage increment of 11.20% and RHA treated clay soil increases continuously with addition of RHA to a percentage increment of 16.2%. BA content leads to a consequent increase in CBR to an optimum value of 9%. The optimum value of RHA content was obtained as 10% with a maximum CBR value of 28.72%. BA treated clay soil increase both CBR and UCS to percentage increment change of 630% and 91.41% respectively while percentage increments of 619.8% and 85.23% were recorded for RHA treated clay soil. BA thus improved the strength properties better in comparison to RHA although in smaller optimum percentage addition.

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Journal articles on the topic 'CBR AGENTS'

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