Search

Purpose: The purpose of this paper is to explore the role of and interaction between (potential) repatriation supporters to develop understanding of how this affects the repatriate experience. Design/methodology/approach: A (single) case study strategy was employed, using a multiple stakeholder approach, involving 21 in-depth interviews in a large UK-based institution with repatriates, home and host HR managers, international human resource (IHR) practitioners and line managers from both home and host locations. Findings: Although line managers, senior managers, family members and third party providers (e.g. relocation agencies, tax advisors) are important for repatriation support, the case study evidence highlights that HR professionals are mainly responsible for the quality of the support delivered by other repatriation supporters. Inadequate support from the headquarters IHR department caused by a lack and unclear information about repatriation procedures and related responsibilities results in insufficient support for home and host HR managers. This negatively impacts repatriates line managers (perceptions of) HR support. Weaknesses in the support chain (headquarter IHR, home and host HR and line managers) are responsible for repatriates (perceived) limited or non-support. Research limitations/implications: The small size of our sample, the single case study design and the method precludes generalisation of the findings. However, the authors’ “look inside” increased the understanding of repatriation support and in particular the support quality. By linking this information to the knowledge of previous studies on organisational support and the devolution of human resource management, the authors are able to identify several topics future studies in the field of repatriation management. Practical implications: IHRM policies have to reflect the role of multiple stakeholders including home and host line managers and HR professionals as well as third party providers and assign clear lines of responsibility to provide a transparent and consistent experience. Repatriates family has to be acknowledged as a stakeholder that has a major influence on repatriation success and failure. Excluding partners and children issues from international career policies has to be considered as a serious HR shortcoming. Second, ensuring timely information regarding return positions. Providing debriefing interviews upon repatriation can help to identify future roles within the organisation. Equally important is exit interviews to explore whether the person has completed an assignment within the previous 24 months and whether this experience has contributed to their decision to leave the organisation. Opportunities to ensure repatriates are being considered for positions as part of the talent pool is crucial. Finally, the authors emphasise the need to acknowledge that third party vendors are part of the repatriation process and must be considered in terms of (perceived) organisational support. Originality/value: This is one of the first studies that highlights the role and interaction of (potential) repatriation supporters. Specifically, this study contributes to addressing three knowledge gaps: it identifies a lack of communication among HR professionals and between them and line managers as a potential source of insufficient organisational support; the findings highlight HR professionals responsibility for supporting line managers and other repatriation supporters in operational repatriation management; and finally, the results support the assumption that HR professionals and line managers own (non-)experience with working abroad might affect the quality of support policies and practices for repatriates.

Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre– and post–CAR-T. We conducted a multicenter retrospective analysis to describe peri–CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post–CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post–CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post–CAR-T cell progression, which remains an unmet clinical need.

•The majority of patients with Hodgkin lymphoma treated in the real world did not receive the planned CDB.•There is no significant association between the CDB frontline therapy and PFS.

-In high-risk patients with relapsed MCL, most of whom received prior BTKi, venetoclax resulted in ORR of 40% and median PFS of 3.7 months.-Patients with MCL who initiate venetoclax should be closely monitored for tumor lysis syndrome.

•Patients with MZL who had M-protein at diagnosis had inferior PFS compared with those with no M-protein.•MZLs producing M-protein at diagnosis have a higher risk of histologic transformation.

A hydrothermal procedure was used to synthesis flower-like 0–0.5 wt% Ni-doped SnS2, oxidation extent of which was tuned in air at 350 °C for various times. Photocatalysts were dip-coated on coiled wire-meshes including a light source for oxidation of 500 ppm trichloroethylene in air. FE-SEM revealed that the SnS2flower-like structure integrity was preserved after partial oxidation, while surface areas were dramatically enhanced. XRD, HR-TEM, Raman, XPS and PL showed formation of fine crystalline nanoparticles and defects by oxidation and resulted in enhanced photocatalytic activity. Band gaps and defects recombination rate of heterostructures were tuned by partial oxidation and Ni doping. 43% oxidation of 0.34 wt% Ni-doped SnS2results in increased surface area by 7.7 times to 100 m2/g, quenched electrons and holes recombination, increased the band gap, and showed the highest TCE conversion of 88%, while the photocatalyst with no oxidation showed no activity. Further addition of Ni declined the surface area and photocatalytic conversion.

Blocking the migration of metastatic cancer cells is a major goal in the therapy of cancer. The receptor tyrosine kinase AXL is one of the main triggers for cancer cell migration in neoplasia of breast, colon, skin, thyroid and prostate. In our study we analyzed the effect of AXL inhibition on cell motility and viability in triple negative breast cancer cell lines overexpressing AXL. Thereby we reveal that the compound BMS777607, exhibiting the lowest IC50values for inhibition of AXL kinase activity in the studied cell lines, attenuates cell motility to a lower extent than the kinase inhibitors MPCD84111 and SKI606. By analyzing the target kinases of MPCD84111 and SKI606 with kinase profiling assays we identified Lyn, a Src family kinase, as a target of both compounds. Knockdown of Lyn and the migration-related CRK-associated substrate (p130Cas), had a significant inhibitory effect on cell migration. Taken together, our findings highlight the importance of combinatorial or multikinase inhibition of non-receptor tyrosine kinases and AXL receptor tyrosine kinase in the therapy of triple negative breast cancer.

The extensively investigated serine/threonine kinase, B-RAF, is a member of the RAS/RAF/MEK/ERK pathway. It plays important role in the regulation of cell growth, differentiation and survival. The mutation of B-RAF occurs frequently in melanomas and colon tumors; therefore, it is considered as an outstanding therapeutic target. In recent years a great number of B-RAF inhibitors have been reported and this number is expected to increase. The aim of our work was to compare the structures and binding mode of the published B-RAF inhibitors, and then to apply the correlations found for the explanation of our experimental results. In the first part of this paper we describe the main pharmacophore features of the co-crysallized B-RAF inhibitors published in the literature, focusing on the binding modes and common structural elements. In the second part we present and characterize our recently developed B-RAF inhibitor family by application of in silico methods and in vitro kinetic profiling. The inhibitory activity of these compounds was determined in biochemical kinase- and cell-based assays. The docking and assay results support our conclusion that the presented compound family belongs to the type I 1/2subgroup, they inhibit B-RAF and B-RAF(V600E) mutant in a sub-micromolar range and most of them show selectivity towards B-RAF(V600E) mutant expressing cell lines with equal or even better IC50 values than sorafenib.

Much has been written about older workers, including how to adequately manage a more mature workforce. Currently, the bulk of research concentrates on the push-pull factors for early retirement vs. the continuation of work life until the pensionable age. This article focuses on a different and rarely investigated group and explicitly addresses an issue up to now overlooked: for those who continue work beyond the age at which full government pension benefits are available (i.e., post-retirement workers), is the meaning of work related to their employment status? To answer this question we compared the work motives of Dutch volunteers and agency workers aged 65 years (i.e., the official Dutch pensionable age) and older. Contrary to the presumptive prevailing common convictions, we found that for post-retirement agency workers financial motives or needs seem less important than personal motives, and the employment status itself is not a good indicator for decision-making on human resource practices. We conclude that for these ‘indisputable seniors' the satisfaction of esteem needs through work remains unremitting, and may even be increasingly important as time goes by.

Age-dependent chlorpyrifos (CPF) metabolism was quantified by in vitro product formation in human hepatic microsomes (ages 13 days to 75 years) and plasma (ages 3 days to 43 years) with gas chromatography-mass spectrometry. Hepatic CPF cytochrome P450 desulfuration [CPF to chlorpyrifos-oxon (CPF-oxon)] and dearylation (CPF to 3,5,6-trichloro-2-pyridinol) Vmaxvalues were 0.35 ± 0.21 and 0.73 ± 0.38 nmol · min–1· mg microsomal protein –1(mean ± S.D.), respectively. The mean (±S.D.) hepatic CPF-oxon hydrolysis (chlorpyrifos-oxonase [CPFOase]) Vmaxwas 78 ± 44 nmol · min–1· mg microsomal protein –1. None of these hepatic measures demonstrated age-dependent relationships on a per microsomal protein basis using linear regression models. Ratios of CPF bioactivation to detoxification (CPF desulfuration to dearylation) Vmaxvalues were consistent across ages. CPFOase in plasma demonstrated age-dependent increases on a volume of plasma basis, as did total plasma protein levels. Mean (±S.D.) CPF-oxon hydrolysis Vmaxvalues for children <6 months of age and adults (≥16 years) were 1900 ± 660 and 6800 ± 1600 nmol · min–1· ml–1, respectively, and at environmental exposure levels, this high- capacity enzyme is likely to be sufficient even in infants. Plasma samples were phenotyped for paraoxonase status, and frequencies were 0.5, 0.4, and 0.1 for QQ, QR, and RR phenotypes, respectively. These results will be integrated into a physiologically based pharmacokinetic and pharmacodynamic model for CPF and, once integrated, will be useful for assessing biological response to CPF exposures across life stages.

Introduction:There is no standard induction therapy in extranodal marginal zone lymphoma (EMZL); current guidelines borrow from follicular lymphoma, where bendamustine and rituximab (BR) is an accepted standard. The data on BR in EMZL is limited (Rummel MJ et al. Lancet2013 & Salar A et al. Blood2017), so we explored BR activity as part of an international consortium.

Hernandez-Ilizaliturri: Astra Zeneca: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Seattle Genetics: Consultancy; Epyzome: Consultancy; Pharmacyclics: Consultancy; Amgen: Consultancy; Gilead: Consultancy.

Epperla: Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Reddy:Genentech, BMS: Research Funding; KITE Pharma, Abbvie, BMS, Celgene: Consultancy. Caimi:Genentech: Research Funding; Celgene Corp: Other: Incyte Corporation - Ownership - Pharmacyclics, Inc. - Ownership - Celgene Corp. - Other, Speakers Bureau; ADC Therapeutics: Research Funding. Greenwell:Lymphoma Research Foundation: Research Funding; Acrotech Biopharma LLC, Kyowa Kirin: Consultancy. Janakiram:Takeda, Fate, Nektar: Research Funding. Olszewski:Genentech, Inc.: Research Funding; Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Cohen:Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo: Consultancy. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Awan:Genentech: Consultancy; Janssen: Consultancy; Astrazeneca: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Gilead Sciences: Consultancy; Kite Pharma: Consultancy; Dava Oncology: Consultancy; Celgene: Consultancy; Blueprint medicines: Consultancy; Sunesis: Consultancy; Karyopharm: Consultancy; MEI Pharma: Consultancy. Barta:Monsanto: Consultancy; Atara: Honoraria; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria. Grover:Genentech: Research Funding; Tessa: Consultancy. Bartlett:Roche/Genentech: Consultancy, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Affimed Therapeutics: Research Funding; Acerta: Consultancy; BTG: Consultancy; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Merck: Research Funding; Forty Seven: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite, a Gilead Company: Research Funding; ADC Therapeutics: Consultancy; Autolus: Research Funding; BMS/Celgene: Research Funding. Christian:Acerta: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Merck: Research Funding; Millenium: Research Funding; MorphoSys: Research Funding; F Hoffman-La Roche: Research Funding; Triphase: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Membership on an entity's Board of Directors or advisory committees; AstraZenica: Membership on an entity's Board of Directors or advisory committees. Herrera:Pharmacyclics: Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Karyopharm: Consultancy.

The Bethesda System of cervical cytologic findings introduced the term ASCUS (atypical squamous cells of undetermined significance) to cover the broad zone separating normal cytomorphology from definitive squamous intraepithelial lesions (SILs). The management of patients with ASCUS is particularly problematic as approximately 10% of ASCUS patients develop SIL and 1 per 1000 develop cervical carcinoma. Our aim was to demonstrate the combined use of polymerase chain reaction for human papillomavirus (HPV) typing and laser scanning cytometry for DNA content measurements in the subcategorization of ASCUS cases according to the risk for progression toward cancer. Liquid- based monolayer preparation (ThinPrep, Cytyc, Boston, MA) of the cytologic material was used for cytomorphologic analysis. DNA content measurements using laser scanning cytometry and direct sequencing of HPV using the consensus primers GP5+/GP6+ and MY09/MY11 were performed from the same material. Twelve of the 44 cases (27.2%) with ASCUS carried a high-risk HPV genome whereas only 3 of the 195 normal control cases (1.5%) showed positivity for a high-risk HPV genome. Six of 12 (50%) of the high-risk HPV-positive ASCUS cases presented isolated cells with a DNA content above 5c, whereas cells with a DNA content above 9c were found in 3 of 12 cases (25%) and were exclusively found in combination with high-risk HPV infection. In these three cases, the histologic follow-up resulted in cervical intraepithelial neoplasia (CIN) I (one case) and CIN III (two cases). None of the other ASCUS or normal cases displayed DNA aneuploidy above 9c. They returned to normal cytology (within normal limits/benign cellular changes) in the follow-up. Human papillomavirus typing and DNA content measurements may delineate a distinct group of ASCUS. Our preliminary data suggest that ASCUS cases with high-risk HPV positivity and with rare cells with abnormally high DNA content represent similar biologic features as high-grade SIL and are at elevated risk to develop cancer. Cancer (Cancer Cytopathol) 2003;99:113–7. © 2003 American Cancer Society.

Infection by high-risk human papillomavirus (HPV) plays a role in the evolution of cervical carcinoma. Cellular atypia and consecutive DNA content alterations in cytologic samples are consequences of a preexisting viral infection. We analyzed the frequency and association of HPV types and the presence of rare cells with abnormally high DNA content. We also evaluated whether these findings support the cytologic diagnosis in 112 routine cases with low and high-grade squamous intraepithelial lesions (LSIL/HSIL) when performed from liquid-based cytologic samples (ThinPrep). For DNA content measurements, laser scanning cytometry was applied and at least 10,000 cells were analyzed. HPV typing was performed by a direct sequencing approach using the consensus primers GP5+/GP6+ and MY09/MY11. Of 112 SIL cases, 110 (98.2%) were HPV positive and 95 (84.8%) had a high-risk type HPV infection. Almost one-half of the cases (46 of 95, 48.4%) with a high-risk HPV infection presented aneuploid squamous cells with greater than 9c DNA content, whereas none of the low-risk HPV-positive or HPV-negative SIL cases showed any aneuploid cells in this range. Although 91.8% of the HSIL cases displayed greater than 9c aneuploid cells, only 7.9% of the LSIL cases were positive for such cells with abnormally high DNA content. HPV typing and DNA measurements help in the objectivation of cytologic atypia and both can be performed efficiently from the same liquid-based cytologic samples. Cancer (Cancer Cytopathol) 2003;99:57–62. © 2003 American Cancer Society.

Background: Measurements on DNA content and steroid receptor status in breast cancer are of great clinical interest. Objective determination of estrogen and progesterone receptor expression should help to define the lowest levels of positivity still responding to adjuvant antihormonal therapy. For this purpose, a simple protocol for laser scanning cytometry is presented. Methods: Analysis of 54 routine breast cancer samples was performed by laser scanning cytometry (LSC). To obtain single cell preparations from fresh tumor tissue, slides were prepared using the Cervisoft cytological device. Exact determination of tumor cell DNA content was done by referring to the CD45-positive tissue leukocyte fraction as the internal diploid reference cell population. Steroid receptor-expressing cells were detected by indirect immunolabeling. Results: Indirect immunofluorescence allowed the best quantification of both the estrogen and progesterone receptor-expressing cell fractions by LSC. The number of receptor-expressing cells could be given in percentage. For comparison, the 10% cutoff value was used to determine receptor positivity. Conclusion: LSC enabled a simple, reliable, and inexpensive determination of DNA index and steroid receptor expression in breast cancer specimens by objective criteria. Cytometry (Clin. Cytometry) 50:210–215, 2002. © 2002 Wiley-Liss, Inc.

There is a need to develop reliable portable analytical systems for biomonitoring lead (Pb) in noninvasively collected saliva samples. In addition, appropriate pharmacokinetic analyses are used to quantitate systemic dosimetry based on the saliva Pb concentrations. A portable microfluidics/electrochemical device was developed for the rapid analysis of Pb based on square wave anodic stripping voltammetry, in which a saliva sample flows over an electrode surface, Pb2+ is chemically reduced and accumulated, and the electric potential of the electrode scanned. The system demonstrates a good linear response over a broad Pb concentration range (1-2000 ppb). To evaluate the relationship between saliva and blood Pb, rats were treated with single oral doses ranging from 20 to 500 mg Pb/kg of body weight, and 24 hours later were administered pilocarpine, a muscarinic agonist to induce salivation. To correlate saliva levels with internal dose, blood and saliva were collected and quantitated for Pb by inductively coupled plasma-mass spectrometry (ICP-MS) and by the microanalytical system. The quantitation with the microanalytical system was slightly less (∼75-85%) than with ICP-MS; however, the response was linear, with concentration suggesting that it can be used for the quantitation of salivary Pb. To facilitate modeling, a physiologically based pharmacokinetic (PBPK) model for Pb was modified to incorporate a salivary gland compartment. The model was capable of predicting blood and saliva Pb concentration based on a limited data set. These results are encouraging, suggesting that once fully developed the microanalytical system coupled with PBPK modeling can be used as important tools for real-time biomonitoring of Pb for both occupational and environmental exposures.

Background:

Background:Patients with primary CNS Lymphoma (PCNSL) often present with neurologic complications such as focal defects, neuropsychiatric symptoms, increased intracranial pressure, aphasia, seizures, and ocular symptoms which require initiation of prophylactic or therapeutic anticonvulsants. Most anticonvulsants are notorious for their pharmacodynamic and pharmacokinetic drug interactions. The cornerstone of PCNSL therapy is the utilization of high-dose methotrexate (HD-MTX). The pharmacokinetics of HD-MTX are uniquely sensitive to both disease biology and drug interactions. Due to the importance of both HD-MTX and anticonvulsants in PCNSL patients, these medications are frequently given in concert with one another despite theoretical and proven drug interactions published in the literature. This is a retrospective analysis of patients treated with a modified R-MPV regimen (rituximab, methotrexate, procarbazine, vincristine alternating with intrathecal methotrexate) and the effects of various anticonvulsants on HD-MTX clearance.

Background:

Immune profiles and immune reconstitution are increasingly studied as important contributors to the prognosis and treatment responses of hematologic malignancy patients. Data on epidemiologic factors influencing immune profiles in hematologic malignancy patients are lacking.

Background:

Background:

Background:The term HGBL, NOS was introduced by the World Health Organization (WHO) in 2016 for aggressive B-cell lymphomas with Burkitt lymphoma-like (BLL) or blastoid cytomorphology that lack double-hit genetics and do not meet criteria for other entities. Diagnostic patterns and prognosis of these rare tumors are not well understood. We examined the characteristics and outcomes of patients (pts) with HGBL, NOS diagnosed in 17 academic centers across the United States.

Introduction

Background.Despite advances in therapy, treatment of R/R NHL remains a challenge. PEVO (TAK924) is a first-in-class, selective, small molecule, NAE inhibitor with preclinical activity in NHL, including mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and diffuse large B cell lymphoma (DLBCL). We and others have demonstrated synergy between PEVO and the Bruton tyrosine kinase inhibitor ibrutinib, in in vitroand in vivomodels of CLL and MCL. We report the results of a phase 1 study of PEVO in combination with ibrutinib in patients with R/R NHL.

Methyltert-butyl ether (MTBE), a fuel additive blended into unleaded gasoline, decreases emissions of selected air pollutants. Exposure to MTBE causes a low incidence of renal tumors in male, but not female, F-344 rats. A number of chemicals that cause male rat-specific renal tumors also cause a syndrome unique to male rats referred to as α2u-globulin (α2u) nephropathy (α2u-N). Previous investigations have demonstrated that MTBE exposure induces a mild accumulation of α2u in male F-344 rats. The objective of the present study was to determine if MTBE, or a metabolite of MTBE, interacts with α2u in male rats administered MTBE orally. Eleven-week-old male and female F-344 rats were administered 750 mg [14C]MTBE/kg body wt or an equivalent volume of 10% emulphor orally for 4 consecutive days. Although [14C]MTBE-treated male rats exhibited a statistically significant increase in renal α2u concentration, the total radioactivity recovered was similar in kidney samples from [14C]MTBE-treated male and female rats. Further analysis of kidney cytosol prepared from [14C]MTBE-treated rats revealed that a slightly greater percentage of radioactivity coeluted on a G-25 gel filtration column with the total protein fraction from male rats than from female rats. Gel filtration (Sephadex G-75 column) and anion exchange chromatography, however, did not demonstrate any coelution of MTBE-derived radioactivity with the low-molecular-weight protein fraction or α2u fraction, respectively, in kidney cytosol prepared from [14C]MTBE-treated male or female rats. Further experimentation using a sealed vial equilibration system demonstrated thatd-limonene oxide, a chemical with a high affinity for α2u, displaced MTBE in male, but not female, rat kidney samples following administration of MTBE. These findings provide indirect evidence that MTBE interacts with a male-specific protein such as α2u in male F-344 rats. Since the pathogenesis of α2u-N is dependent on the formation of a reversibly bound chemical–α2u complex, demonstration of anin vivointeraction of MTBE or one of its metabolites with α2u supports the α2u mechanism as a cause of MTBE-induced protein droplet nephropathy in male rats.

Methyltert-butyl ether (MTBE) is a gasoline additive that causes renal tumors in male rats. In the process of measuring chemical specific parameters necessary to develop a quantitative dosimetry model of MTBE in rats, the uptake of MTBE was found to be 5.5 times greater in male than in female F-344 rat kidney homogenate. The objectives of this study were to characterize the factor(s) that influences the high uptake of MTBE into male rat kidneyin vitroand to develop a system to evaluate the interaction of MTBE with the male rat-specific protein, α2u-globulin (α2u). The uptake of MTBE in male, but not female, rat kidney homogenate was found to be dependent on protein and chemical concentrations. When [14C]MTBE was incubated with male rat kidney homogenate, radioactivity coeluted with the total protein fraction on a gel filtration column. An interaction between [14C]MTBE and male rat kidney proteins was not found under conditions of dialysis or anion exchange chromatography. A two-compartment vial equilibration model was used to assess the interaction between MTBE and α2u. Using this system, the dissociation constant for MTBE and α2u was estimated to be 2.15 × 10−4m, which is in the range of other chemicals known to bind to α2u and cause α2u-mediated nephropathy.d-Limonene oxide was used to validate this two-compartment vial equilibration system. These findings illustrate a technique useful in estimating the dissociation constant for a volatile chemical and a protein, as well as explain the process that contributes to the uptake of MTBE into male rat kidney homogenatein vitro.A description of the weak interaction between MTBE and α2u will be used to refine a physiologically based pharmacokinetic model to describe the target tissue (kidney) concentrations of MTBE.