Xanthohumol inhibits cell proliferation and induces apoptosis in human thyroid cells.

The cell growth inhibitory potential of xanthohumol (XN), a natural prenylflavonoid present in hops and beer, on human papillary thyroid cancer cells is reported. We demonstrate that XN decreases the proliferation of TPC-1 cancer cells in a dose and time dependent manners. At low concentration (10 μM) XN was shown to significantly inhibit carcinogenesis by a mechanism that stops or slows down cell division, preserving the viability of the cells.

CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.

The T lineage glycoprotein CD6 is generally considered to be a costimulator of T-cell activation. Here, we demonstrate that CD6 significantly reduces early and late T-cell responses upon superantigen stimulation or TCR triggering by Abs. Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor.

Morphine versus midazolam as upfront therapy to control dyspnea perception in cancer patients while its underlying cause is sought or treated.

Context: Cancer patients with dyspnea may be able to have the symptom pharmacologically controlled while its underlying cause is sought or treated.

Objectives: This study was done to determine whether symptom control can be achieved while the cause is evaluated or treated and whether morphine or midazolam would be more suitable in this setting.

Methods: Sixty-three ambulatory patients with advanced cancer and dyspnea were clinically characterized and then randomized to receive either oral morphine or oral midazolam.

Molecular cloning and analysis of SSc5D, a new member of the scavenger receptor cysteine-rich superfamily.

Glycoproteins of the scavenger receptor cysteine-rich (SRCR) superfamily contain one or more protein modules homologous to the membrane-distal domain of macrophage scavenger receptor I. These domains can be found in the extracellular regions of membrane proteins and in secreted glycoproteins, from the most primitive species to vertebrates. A systematic, bioinformatics-based search for putative human proteins related to the forty-seven known human group B SRCR domains identified a new family member that we have called Soluble Scavenger with 5 Domains (SSc5D).

Molecular detection of circulating tyrosinase mRNA: optimization in a preclinical xenograft mouse melanoma model and further evaluation in samples from advanced melanoma patients.

We designed high-affinity primers for the mRNA sequence of human tyrosinase to test the value of molecular detection of circulating melanoma cells by reverse transcription-polymerase chain reaction (RT-PCR). The optimization process included in vitro settings and in vivo studies in a xenograft mouse model. We detected tyrosinase expression with at least 40 pg and 1.

Protein interactions between CD2 and Lck are required for the lipid raft distribution of CD2.

In T lymphocytes, lipid rafts are preferred sites for signal transduction initiation and amplification. Many cell membrane receptors, such as the TCR, coreceptors, and accessory molecules associate within these microdomains upon cell activation. However, it is still unclear in most cases whether these receptors interact with rafts through lipid-based amino acid modifications or whether raft insertion is driven by protein-protein interactions.

Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer.

Under the common denomination of Systemic Immune-Metabolic Syndrome (SIMS), we grouped many symptoms that share a similar pathophysiologic background. SIMS is the result of the dysfunctional interaction of tumor cells, stroma cells, and the immune system, leading to the release of cytokines and other systemic mediators such as eicosanoids. SIMS includes systemic syndromes such as paraneoplastic hemopathies, hypercalcemia, coagulopathies, fatigue, weakness, cachexia, chronic nausea, anorexia, and early satiety among others.

Extracellular isoforms of CD6 generated by alternative splicing regulate targeting of CD6 to the immunological synapse.

The great majority of mammalian genes yield multiple transcripts arising from differential mRNA processing, but in very few instances have alternative forms been assigned distinct functional properties. We have cloned and characterized a new isoform of the accessory molecule CD6 that lacks the CD166 binding domain and is expressed in rat and human primary cells. The novel isoform, CD6Deltad3, results from exon 5 skipping and consequently lacks the third scavenger receptor cysteine-rich (SRCR) domain of CD6.

The contribution of conformational adjustments and long-range electrostatic forces to the CD2/CD58 interaction.

CD2 is a T cell surface molecule that enhances T and natural killer cell function by binding its ligands CD58 (humans) and CD48 (rodents) on antigen-presenting or target cells. Here we show that the CD2/CD58 interaction is enthalpically driven and accompanied by unfavorable entropic changes. Taken together with structural studies, this indicates that binding is accompanied by energetically significant conformational adjustments.

Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding protein, CD48.

The structural analysis of surface proteins belonging to the CD2 subset of the immunoglobulin superfamily has yielded important insights into transient cellular interactions. In mice and rats, CD2 and CD244 (2B4), which are expressed predominantly on T cells and natural killer cells, respectively, bind the same, broadly expressed ligand, CD48. Structures of CD2 and CD244 have been solved previously, and we now present the structure of the receptor-binding domain of rat CD48.

Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer.

Purpose: We performed this double-blinded, placebo-controlled study to determine the safety and efficacy of L-alanyl-L-glutamine in the prevention of mucositis in patients with head-and-neck cancer.

Methods And Materials: Thirty-two patients with head-and-neck cancer were treated with chemoradiotherapy (CRT) (radiotherapy daily up to 70 Gy plus cisplatin/5-fluoruracil once a week) and were asked to participate. Twenty-nine patients received the CRT schedule and were double-blindly assigned to receive either intravenous L-alanyl-L-glutamine 0.

Cellular and humoral immune response to N-Glycolyl-GM3 elicited by prolonged immunotherapy with an anti-idiotypic vaccine in high-risk and metastatic breast cancer patients.

In this study, the immunogenicity and toxicity profile of 1E10, an anti-idiotypic vaccine mimicking the N-glycolyl-GM3 ganglioside, was investigated with an extended vaccination protocol. The year-long vaccination scheme consisted of 6 biweekly intradermal injections (induction phase), followed by 10 monthly boosters (maintenance). Nineteen patients with high-risk (stage III) or metastatic breast cancer were vaccinated with different dose levels of 1E10 (0.

Midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in patients with advanced cancer.

The mainstay of dyspnea palliation remains altering its central perception. Morphine is the main drug and anxiolytics have a less established role. This trial assessed the role of midazolam as adjunct therapy to morphine in the alleviation of severe dyspnea perception in terminally ill cancer patients.

Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases.

Purpose: The primary goal of this phase I/II study was to evaluate the feasibility, safety and efficacy of celecoxib administered concomitant to radiotherapy to treat unresectable BM.

Patients And Methods: Patients with measurable BM by CT or MRI, unresectability criteria by a neurosurgeon and RPA-RTOG class II were eligible. Celecoxib was administered at 400 mg/day during the entire course of radiotherapy.

OX52 is the rat homologue of CD6: evidence for an effector function in the regulation of CD5 phosphorylation.

The MRC OX52 monoclonal antibody is a marker of rat T lymphocytes. We have cloned by polymerase chain reaction the rat homologue of CD6, and fluorescein-activated cell sorter analysis and immunoprecipitations using OX52 in COS7 cells transfected with rat CD6 cDNA showed that CD6 is the cell-surface molecule recognized by OX52. Immunoprecipitation analysis showed that CD6 coprecipitated with CD5, which in turn, was coprecipitated equivalently with CD2, CD6, and the T cell receptor (TCR), but the fraction of CD5 associated with CD6 was highly phosphorylated in kinase assays, in marked contrast with the low level of phosphorylation of CD5 associated with TCR or CD2.

CD2 physically associates with CD5 in rat T lymphocytes with the involvement of both extracellular and intracellular domains.

T lymphocytes can be activated and induced to proliferate through stimulation of the CD2 glycoprotein with functional combinations of CD2 antibodies. However, this mechanism of signal transduction via CD2 is still not fully understood. We have investigated which molecules on the T cell surface preferentially associate in Cis with CD2 and may regulate its signaling properties.