Additional file 1: of Bortezomib resistance in multiple myeloma is associated with increased serine synthesis

Supplemental information. Supplemental Methods; Figure S1. Response of RPMI-8226 WT, BTZ/7 and BTZ/100 cells to bortezomib and other chemotherapeutic agent; Figure S2. Intra- and extracellular metabolite analysis of BTZ- and CFZ-resistant cell lines; Figure S3. Response to serine starvation of RPMI-8226 WT and BTZ/100 cells; Figure S4. Bortezomib resistance correlates to the expression of PHGDH; Table S1. Characteristics of multiple myeloma patients; Table S2. Upregulated metabolic enzymes in RPMI-8226 BTZ/100 and BTZ/7 cells compared to WT; Table S3. Downregulated metabolic enzymes in RPMI-8226 BTZ/100 and BTZ/7 cells compared to WT. (PDF 6298 kb

The need for information among patients with hematological malignancies: Psychometric analyses of the 62-item Hematology Information Needs Questionnaire (HINQ-62)

<div><p>The purpose of this study was to investigate the psychometric characteristics (content validity, internal consistency, and subscale structure) of the Hematology Information Needs Questionnaire-62 (HINQ-62), a patient reported outcome measure (PROM) for assessing the need for information among patients with hematological malignancies (HM-patients). Baseline data were used from a prospective study on the need for information which 336 newly diagnosed HM-patients had completed. In phase 1 (design phase), data from the first 135 patients were used and in phase 2 (validation phase), data from the remaining 201 HM patients were used. Content validity was analyzed by examining irrelevance of items. Items were considered irrelevant if more than 10% of the patients scored totally disagree on that item. The subscale structure of the HINQ-62 was investigated with Factor analysis (FA) (exploratory FA in phase 1 and confirmatory FA in phase 2). Cronbach’s α was computed for the different subscales and >.70 was considered as good internal consistency. None of the 62 HINQ-items were irrelevant. Exploratory FA identified five subscales: “Disease, symptoms, treatment and side-effects”, “Etiology, sleep and physical changes”, “Self-care”, “Medical tests and prognosis”, and “Psychosocial”. Root Mean Square Error of Approximation (RMSEA) among patients was 0.037 in phase 1 and 0.045 in phase 2. The comparative fit index (CFI)/Tucker-Lewis index -non-normed fit index among patients was 0.984/0.983 and 0.948/0.946, in phase 1 and 2 respectively. The internal consistency of the subscales was good, with Cronbach’s α 0.82–0.99. The HINQ is a valid PROM for assessing the need for information among Dutch HM-patients at diagnosis.</p></div

Overview of sociodemographic and clinical characteristics of patients of phase 1 (n = 135) and phase 2 (n = 201).

<p>Overview of sociodemographic and clinical characteristics of patients of phase 1 (n = 135) and phase 2 (n = 201).</p

Internal consistency (Cronbach’s α) of subscales of the HINQ.

<p>Internal consistency (Cronbach’s α) of subscales of the HINQ.</p

Factor loadings of the items on the Hematology Information Needs Questionnaire for study 1.

<p>Factor loadings of the items on the Hematology Information Needs Questionnaire for study 1.</p

Mean (range) missing item responses of the HINQ-62 in phase 1 and 2.

<p>Mean (range) missing item responses of the HINQ-62 in phase 1 and 2.</p

Fit indices of the HINQ.

<p>Fit indices of the HINQ.</p

Performance of ⁸⁹Zr-Labeled-Rituximab-PET as an Imaging Biomarker to Assess CD20 Targeting: A Pilot Study in Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma

<div><p>Purpose</p><p>Treatment of patients with diffuse large B cell lymphoma (DLBCL) includes rituximab, an anti-CD20 monoclonal antibody (mAb). Insufficient tumor targeting might cause therapy failure. Tumor uptake of ⁸⁹Zirconium (⁸⁹Zr)-mAb is a potential imaging biomarker for tumor targeting, since it depends on target antigen expression and accessibility. The aim of this pilot study was to describe the performance of ⁸⁹Zr-labeled-rituximab-PET to assess CD20 targeting in patients with relapsed/refractory DLBCL.</p><p>Methods</p><p>Six patients with biopsy-proven DLBCL were included. CD20 expression was assessed using immunohistochemistry (IHC). 74 MBq ⁸⁹Zr-rituximab (10 mg) was administered after the therapeutic dose of rituximab. Immuno-PET scans on day 0, 3 and 6 post injection (D0, D3 and D6 respectively) were visually assessed and quantified for tumor uptake.</p><p>Results</p><p>Tumor uptake of ⁸⁹Zr-rituximab and CD20 expression were concordant in 5 patients: for one patient, both were negative, for the other four patients visible tumor uptake was concordant with CD20-positive biopsies. Intense tumor uptake of ⁸⁹Zr-rituximab on PET (SUV_peak = 12.8) corresponded with uniformly positive CD20 expression on IHC in one patient. Moderate tumor uptake of ⁸⁹Zr-rituximab (range SUV_peak = 3.2–5.4) corresponded with positive CD20 expression on IHC in three patients. In one patient tumor uptake of ⁸⁹Zr-rituximab was observed (SUV_peak = 3.8), while the biopsy was CD20-negative.</p><p>Conclusions</p><p>This study suggests a positive correlation between tumor uptake of ⁸⁹Zr-rituximab and CD20 expression in tumor biopsies, but further studies are needed to confirm this. This result supports the potential of ⁸⁹Zr-rituximab-PET as an imaging biomarker for CD20 targeting. For clinical application of ⁸⁹Zr-rituximab-PET to guide individualized treatment, further studies are required to assess whether tumor targeting is related to clinical benefit of rituximab treatment in individual patients.</p></div

Biopsies ranked in order of increasing CD20 expression.

<p>Per panel the CD20 rank is indicated in the right upper corner and the patient number in the left lower corner. 1) Core-needle biopsy of DLBCL (liver) in patient 1 shows completely absent CD20 expression. 2) Core-needle biopsy of DLBCL (axillar lymph node) in patient 6 showing almost completely absent CD20 expression: extremely sparse groups of CD20-positive tumor cells with granular staining pattern, considered as absent CD20 expression. 3) Excision biopsy of DLBCL (cervical lymph node) in patient 2 shows heterogeneously positive CD20 expression in sparse groups of cells, granular staining pattern. 4) Excision biopsy of DLBCL (nasopharynx) in patient 5 showing heterogeneously positive CD20 expression in the majority of cells, membranous staining pattern. 5) Excision biopsy of DLBCL (retroperitoneal lymph node) in patient 4 showing uniformly positive CD20 expression, membranous staining pattern. 6) Excision biopsy of DLBCL (inguinal lymph node) in patient 3 showing uniformly positive CD20 expression, membranous staining pattern.</p

Quality controls of ⁸⁹Zr-rituximab.

<p>Quality controls of ⁸⁹Zr-rituximab.</p