Lung cancer volume doubling time by computed tomography: A systematic review and meta-analysis.

Aim: Lung cancer growth rate influences screening strategies and treatment decisions. This review aims to provide an overview of primary lung cancer growth rate, quantified by volume doubling time (VDT) through computed tomography (CT) measurement.

Methods: Using PRISMA-DTA guideline, PubMed, EMBASE, and Web of Science were searched until March 2024 for studies reporting CT-measured VDT of pathologically confirmed primary lung cancer before intervention.

Outstanding negative prediction performance of solid pulmonary nodule volume AI for ultra-LDCT baseline lung cancer screening risk stratification.

Objective: To evaluate performance of AI as a standalone reader in ultra-low-dose CT lung cancer baseline screening, and compare it to that of experienced radiologists.

Methods: 283 participants who underwent a baseline ultra-LDCT scan in Moscow Lung Cancer Screening, between February 2017-2018, and had at least one solid lung nodule, were included. Volumetric nodule measurements were performed by five experienced blinded radiologists, and independently assessed using an AI lung cancer screening prototype (AVIEW LCS, v1.

High-pitch versus sequential mode for coronary calcium in individuals with a high heart rate: Potential for dose reduction.

Background: To determine the impact of high-pitch spiral acquisition on radiation dose and cardiovascular disease (CVD) risk stratification by coronary artery calcium (CAC) assessment with computed tomography in individuals with a high heart rate.

Methods: Of the ROBINSCA trial, 1990 participants with regular rhythm and heart rates >65 beats per minute (bpm) were included. As reference, 390 participants with regular heart rates ≤65 bpm were used.

Coronary Artery Calcium Imaging in the ROBINSCA Trial: Rationale, Design, and Technical Background.

Rationale And Objectives: To describe the rationale, design, and technical background of coronary artery calcium (CAC) imaging in the large-scale population-based cardiovascular disease screening trial (Risk Or Benefit IN Screening for CArdiovascular Diseases [ROBINSCA]).

Materials And Methods: First, literature search was performed to review the logistics, setup, and settings of previously performed CAC imaging studies, and current clinical CAC imaging protocols of participating centers in the ROBINSCA trial were evaluated. A second literature search was performed to evaluate the impact of computed tomography parameter settings on CAC score.

CD4+ T-cell alloreactivity toward mismatched HLA class II alleles early after double umbilical cord blood transplantation.

Although double umbilical cord blood transplantation (dUCBT) in adult patients may be associated with less graft failure compared with single UCBT, hematopoietic recovery generally originates from a single cord blood unit (CBU). CBU predominance is still incompletely understood. We recently showed that blood CD4 T-cell numbers rapidly increase after dUCBT, and early CD4 T-cell chimerism predicts for graft predominance.

Long-term stability of T-cell activation and transduction components critical to the processing of clinical batches of gene-engineered T cells.

Background Aims: The generation of gene-modified T cells for clinical adoptive T-cell therapy is challenged by the potential instability and concomitant high financial costs of critical T-cell activation and transduction components. As part of a clinical trial to treat patients with metastatic renal cell cancer with autologous T cells engineered with a chimeric antigen receptor (CAR) recognizing carboxy-anhydrase-IX (CAIX), we evaluated functional stability of the retroviral vector, T-cell activation agent Orthoclone OKT3 (Janssen-Cilag, Beerse, Belgium) monoclonal antibody (mAb) and the transduction promoting agent RetroNectin (Takara, Otsu, Japan).

Methods: Carboxy-anhydrase-IX chimeric antigen receptor retrovirus-containing culture supernatants (RTVsups) were generated from two packaging cell lines, Phoenix-Ampho (BioReliance, Sterling, UK) and PG13, and stored at -80°C over 10 years and 14 years.

KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue.

Although anti-EGFR therapy has established efficacy in metastatic colorectal cancer, only 10-20% of unselected patients respond. This is partly due to KRAS and BRAF mutations, which are currently assessed in the primary tumor. To improve patient selection, assessing mutation status in circulating tumor cells (CTCs), which possibly better represent metastases than the primary tumor, could be advantageous.

Double umbilical cord blood transplantation: a study of early engraftment kinetics in leukocyte subsets using HLA-specific monoclonal antibodies.

Single cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the different leukocyte subsets and the mechanism of graft predominance is largely unknown. To investigate whether a differential engraftment might reveal a specific subset that could play a key role in the mechanism of graft predominance, we studied early engraftment kinetics of different leukocyte subpopulations by flow cytometry using human monoclonal antigen-specific human leukocyte antigen antibodies, directed against mismatched human leukocyte antigen-A or -B antigens between recipient and CBUs.

Inflammation and fatigue dimensions in advanced cancer patients and cancer survivors: an explorative study.

Background: Inflammation may underlie cancer-related fatigue; however, there are no studies that assess the relation between fatigue and cytokines in patients with advanced disease versus patients without disease activity. Furthermore, the relation between cytokines and the separate dimensions of fatigue is unknown. Here, association of plasma levels of inflammatory markers with physical fatigue and mental fatigue was explored in advanced cancer patients and cancer survivors.

Insufficient recovery of thymopoiesis predicts for opportunistic infections in allogeneic hematopoietic stem cell transplant recipients.

Background: Recovery of thymopoiesis after allogeneic hematopoietic stem cell transplantation is considered pivotal for full immune competence. However, it is still unclear to what extent insufficient recovery of thymopoiesis predicts for subsequent opportunistic infections and non-relapse mortality.

Design And Methods: A detailed survey of all post-engraftment infectious complications, non-relapse mortality and overall survival during long-term follow-up was performed in 83 recipients of allogeneic stem cell grafts after myeloablative conditioning.

mRNA levels of CD31, CD144, CD146 and von Willebrand factor do not serve as surrogate markers for circulating endothelial cells.

Circulating endothelial cells (CEC) are considered a promising marker to determine the extent of vascular damage. However, currently available and validated CEC enumeration assays are laborious, time consuming and costly, which limits their clinical utility. Here, we evaluated the feasibility of quantifying mRNA levels of the endothelium-associated markers CD31, CD144, CD146 and von Willebrand factor (vWf) in peripheral blood (PB) of healthy donors, patients, and human umbilical veins by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and their use as surrogate markers for CEC.

Review of a large clinical series: the value of routinely obtained chest radiographs on admission to a mixed medical--surgical intensive care unit.

Background And Objectives: The efficacy of routinely obtained chest radiographs (CXRs) on admission to the intensive care unit (ICU) is largely unknown. The current study investigated the efficacy of routinely obtained admission CXRs and determined whether the value of this diagnostic test was dependent on patient category.

Materials And Methods: Prospective nonrandomized controlled study.

Detection of circulating tumor cells in breast cancer may improve through enrichment with anti-CD146.

Most assays to detect circulating tumor cells (CTCs) rely on EpCAM expression on tumor cells. Recently, our group reported that in contrast to other molecular breast cancer subtypes, "normal-like" cell lines lack EpCAM expression and are thus missed when CTCs are captured with EpCAM-based technology [J Natl Cancer Inst 101(1):61-66, 2009]. Here, the use of CD146 is introduced to detect EpCAM-negative CTCs, thereby improving CTC detection.

Circulating tumor cells (CTCs): detection methods and their clinical relevance in breast cancer.

The enumeration of circulating tumor cells has long been regarded as an attractive diagnostic tool, as circulating tumor cells are thought to reflect aggressiveness of the tumor and may assist in therapeutic decisions in patients with solid malignancies. However, implementation of this assay into clinical routine has been cumbersome, as a validated test was not available until recently. Circulating tumor cells are rare events which can be detected specifically only by using a combination of surface and intracellular markers, and only recently a number of technical advances have made their reliable detection possible.

Gibbon ape leukemia virus poorly replicates in primary human T lymphocytes: implications for safety testing of primary human T lymphocytes transduced with GALV-pseudotyped vectors.

The Food and Drug Administration/Center for Biologics Evaluation and Research has defined that for retroviral gene therapy, the vector-producing cell, the vector preparation, and the ex vivo gene-transduced cells have to be tested for absence of replication-competent retrovirus (RCR) if the transduced cells are cultured for >4 days. We assessed the sensitivity of the "extended PG4(S+L-) assay" to detect gibbon ape leukemia virus (GALV) RCR, and applied this assay to measure GALV RCR spread in retrovirally transduced T cells. To this end, T cells were expanded for 12 days after transduction with a GALV-envelope pseudotyped retroviral vector expressing single chain variable fragment (anticarbonic anhydrase IX) in presence or absence of GALV RCR.

Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells.

Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling-normal-like, basal, HER2-positive, and luminal A and B-were identified by CellSearch, a US Food and Drug Administration-approved test that uses antibodies against the cell surface-expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells.

Molecular characterization of circulating tumor cells in large quantities of contaminating leukocytes by a multiplex real-time PCR.

Detection of circulating tumor cells (CTCs) in whole blood from metastatic cancer patients by the CellSearch CTC Test (Veridex LLC, Warren, NJ, USA) has been shown to have clinical relevance. In addition to enumeration, there is great interest in molecular characterization of these CTCs. We aimed to establish a robust method to perform mRNA expression analysis of multiple genes by a real-time reverse transcriptase (RT)-PCR on small numbers of CTCs enriched from whole blood by the CellSearch system.

Selection of human antibody fragments directed against tumor T-cell epitopes for adoptive T-cell therapy.

Adoptive transfer of antigen-specific T-cells has shown therapeutic successes in the treatment of tumors in patients with metastatic melanoma. Tumor antigen-specific T-lymphocytes, however, occur only at low frequencies in a small proportion of patients. This low T-lymphocyte frequency together with the difficulties associated with in vitro generation of T-lymphocytes specific for cancers other than melanoma hampers adoptive T cell therapy.

Human TCR that incorporate CD3zeta induce highly preferred pairing between TCRalpha and beta chains following gene transfer.

TCR gene therapy is adversely affected by newly formed TCRalphabeta heterodimers comprising exogenous and endogenous TCR chains that dilute expression of transgenic TCRalphabeta dimers and are potentially self-reactive. We have addressed TCR mispairing by using a modified two-chain TCR that encompasses total human CD3zeta with specificities for three different Ags. Transfer of either TCRalpha:CD3zeta or beta:CD3zeta genes alone does not result in surface expression, whereas transfer of both modified TCR chains results in high surface expression, binding of peptide-MHC complexes and Ag-specific T cell functions.

B and T cell imbalances in CSF of patients with Hu-antibody associated PNS.

In paraneoplastic neurological syndromes associated with Hu-antibodies (Hu-PNS) an important role for cellular immunity is hypothesized. We characterized the cerebrospinal fluid (CSF) pleocytosis in Hu-PNS patients by assessing the major lymphocyte subsets by flow cytometry. The B cell subset in the CSF of Hu-PNS patients showed a significant absolute (approximately 20x) and relative (approximately 3x) expansion, while the numbers of CD4+ T cells, CD8+ T cells and NK cells only showed an absolute expansion (approximately 4-7x) compared to the controls.

Circulating tumour cell detection on its way to routine diagnostic implementation?

Circulating tumour cells (CTCs) have been considered for a long time in reflecting the aggressiveness of tumours. As a result, many attempts have been made to develop assays that reliably detect and enumerate CTCs, but only recently have such assays been available. The first clinical results obtained with such assays strongly suggest that in some tumour types, CTC detection and enumeration can be used to estimate prognosis and may serve as an early marker to assess anti-tumour activity of a treatment.

Gene-modified T cells for adoptive immunotherapy of renal cell cancer maintain transgene-specific immune functions in vivo.

Background: We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)], and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the in vivo activity of the infused scFv(G250)(+) T cells is reflected by changes of selected immune parameters measured in peripheral blood.

Methods: ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients during and after treatment were compared to the same functions of scFv(G250)(+) T lymphocytes prior to infusion, and were correlated with plasma cytokine levels.

Twenty years of external quality assurance in clinical cell analysis--a tribute to Jean-Luc D'Hautcourt.

External quality assurance (EQA) programs in clinical cell analysis are now a consolidated item of laboratory practice. All the flow cytometric testings with an impact on clinical decision making have been submitted to regular EQA programs during the last 20 years, and this has produced internationally homogeneous guidelines, with a remarkable improvement in result reproducibility.Jean-Luc D'Hautcourt was a pioneer in this field, and his valuable contributions to flow cytometric method standardization and to the dissemination of the educational aspects of EQA programs are recognized.

T cell re-targeting to EBV antigens following TCR gene transfer: CD28-containing receptors mediate enhanced antigen-specific IFNgamma production.

EBV is associated with a broad range of malignancies. Adoptive immunotherapy of these tumors with EBV-specific CTL proved useful. We generated a panel of primary human T cells specific to various EBV antigens (i.

An uncontrolled trial of rituximab for antibody associated paraneoplastic neurological syndromes.

Anti-CD20 monoclonal antibody (rituximab) is effectively used in the treatment of B-cell lymphomas. Recent reports in the literature suggest that antibody associated autoimmune disorders may respond to rituximab. We therefore treated nine patients with anti-Hu or anti-Yo associated paraneoplastic neurological syndromes (PNS) with a maximum of four monthly IV infusions of rituximab (375mg/m(2)).