Dostarlimab for the treatment of endometrium cancer and other solid tumors.

The use of monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, programmed cell death 1 ligand 1 (PD-L1), widely extends to a large number of tumors such as melanoma, non-small cell lung, renal or lymphomas, among others. Some of them are already approved as first- or second-line treatment, as pembrolizumab, nivolumab or cemiplimab. Dostarlimab is an investigational humanized anti-PD-1 that is being developed both in monotherapy and as combination therapy, for gynecological tumors but also for lung cancer or melanoma. The preliminary results, particularly in endometrial cancer, show a high affinity against PD-1 with encouraging clinical activity. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.

Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

Active angiogenesis in metastatic renal cell carcinoma predicts clinical benefit to sunitinib-based therapy.

BACKGROUND: Sunitinib represents a widely used therapy for metastatic renal cell carcinoma patients. Even so, there is a group of patients who show toxicity without clinical benefit. In this work, we have analysed pivotal molecular targets involved in angiogenesis (vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (KDR), phosphorylated (p)KDR and microvascular density (MVD)) to test their potential value as predictive biomarkers of clinical benefit in sunitinib-treated renal cell carcinoma patients. METHODS: Vascular endothelial growth factor-A, KDR and pKDR-Y1775 expression as well as CD31, for MVD visualisation, were determined by immunohistochemistry in 48 renal cell carcinoma patients, including 23 metastatic cases treated with sunitinib. Threshold was defined for each biomarker, and univariate and multivariate analyses for progression-free survival (PFS) and overall survival (OS) were carried out. RESULTS: The HistoScore mean value obtained for VEGF-A was 121.6 (range, 10-300); for KDR 258.5 (range, 150-300); for pKDR-Y1775 10.8 (range, 0-65) and the mean value of CD31-positive structures for MVD visualisation was 49 (range, 10-126). Statistical differences for PFS (P=0.01) and OS (P=0.007) were observed for pKDR-Y1775 in sunitinib-treated patients. Importantly, pKDR-Y1775 expression remained significant after multivariate Cox analysis for PFS (P=0.01; HR: 5.35, 95% CI, 1.49-19.13) and for OS (P=0.02; HR: 5.13, 95% CI, 1.25-21.05). CONCLUSIONS: Our results suggest that the expression of phosphorylated (i.e., activated) KDR in tumour stroma might be used as predictive biomarker for the clinical outcome in renal cell carcinoma first-line sunitinib-treated patients.

Prevalencia de enfermedad por reflujo gastroesofágico en la población adulta Venezolana

La enfermedad por reflujo gastroesofágico (ERGE) es una enfermedad crónica recurrente, que constituye uno de los trastornos gastrointestinales que afecta con mayor frecuencia a población mundial. Objetivo: Determinar la prevalencia de enfermedad por reflujo gastroesofágico en la población adulta venezolana. Pacientes y Métodos: Se realiza un estudio descriptivo, de corte transversal, multicéntrico durante los meses de abril y mayo de 2008. Se entrevistaron a individuos en edades comprendidas entre 15 - 65 años de diferentes estados del país (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) escogidos a través del azar simple, realizándose un muestreo por conglomerados, de donde, en cada estado se seleccionó un Municipio y de éste, lugares como iglesias, centro comerciales, cines y paradas de autobuses. Se tomó en consideración la población de cada municipio según el Censo Nacional 2001. Resultados: Un total de 1318 individuos fueron encuestados en los estados incluidos, 814 mujeres (61,76%) y 504 Hombres (38,24%). En cuanto a la distribución por categoría de edad, el grupo de 25-35 años constituyó el de mayor predominio. Se obtuvo una Prevalencia Nacional de 11,54%, donde los síntomas cardinales pirosis y regurgitación ácida representaron 16,62% y 12,75% respectivamente. Conclusión: La prevalencia nacional de enfermedad por reflujo gastroesofágico en la población venezolana es del 11,54%.

The gastroesophageal reflux disease (GERD) is a chronic recurrent illness that represents one of the most common gastrointestinal disorders that affects worldwide population. Aim: To determine the prevalence of gastroesophageal reflux disease in the Venezuelan adult population. Patients and Methods: A Descriptive, cross section, multicentric study was made. A survey was done to people in ages between 15 - 65 years of different states of the country (Aragua, Anzoátegui, Barinas, Carabobo, Delta Amacuro, Distrito Capital, Mérida, Miranda, Sucre, Zulia) chosen randomly. Cluster sampling was performed, where in each State was selected a municipality and, of which one places like churches, malls, cinemas and bus stops. To calculate de amount of people The National Census 2001 was taken in account in each municipality. Results: A total of 1318 individuals were surveyed in the mentioned States including, 814 women (61.76%) and 504 men (38.24%). The predominant distribution by age was the group of 25-35 years old. A National Prevalence of 11.54% was obtained, where the cardinal symptoms were heartburn and acid regurgitation represented 16.62% and 12.75% respectively. Conclusion: The national prevalence of gastroesophageal reflux disease in the Venezuelan adult population is 11.54%.

Biweekly docetaxel and gemcitabine as neoadjuvant chemotherapy followed by adjuvant doxorubicin and cyclophosphamide therapy in stage II and III breast cancer patients: results of a phase II study.

INTRODUCTION: The purpose of this phase II study was to evaluate the efficacy and safety of neoadjuvant docetaxel/gemcitabine treatment in a biweekly regimen. MATERIALS AND METHODS: Patients with stage II/III breast cancer were treated with docetaxel (65 mg/m(2)) followed by gemcitabine (2500 mg/m(2)) every 2 weeks for 6 cycles. Patients with a clinical response or stable disease underwent mastectomy or breast-conserving surgery plus axillary dissection. After surgery, patients received 4 cycles of standard doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. RESULTS: Thirty-five patients were included in the trial. The overall response rate was 71.4% (95% CI: 53.7-85.4), with 8 complete and 17 partial responses. Breast conservation was possible in 59% of the patients. Toxicity was manageable. CONCLUSIONS: We consider biweekly docetaxel and gemcitabine could be an active and tolerable regimen option in the neoadjuvant setting sequentially with standard adjuvant doxorubicin-cyclophosphamide in patients with stage II or III breast cancer.

Receptor-receptor interactions involving adenosine A1 or dopamine D1 receptors and accessory proteins.

The molecular basis for the known intramembrane receptor-receptor interactions among heptahelical receptors (G protein coupled receptors, GPCR) was postulated to be heteromerization based on receptor subtype specific interactions between different types of homomers of GPCR. Adenosine and dopamine receptors in the basal ganglia have been fundamental to demonstrate the existence of receptor heteromers and the functional consequences of such molecular interactions. The heterodimer is only one type of heteromeric complex and the evidence is equally compatible with the existence of higher order heteromeric complexes, where also adapter proteins such as homer proteins and scaffolding proteins can exist, assisting in the process of linking the GPCR and ion channel receptors together in a receptor mosaic that may have special integrative value and may constitute the molecular basis for learning and memory. Heteromerization of D(2) dopamine and A(2A) adenosine receptors is reviewed by Fuxe in another article in this special issue. Here, heteromerization between D(1) dopamine and A(1) adenosine receptors is reviewed. Heteromers formed by dopamine D(1) and D(2) receptors and by adenosine A(1) and A(2A) receptors also occur in striatal cells and open new perspectives to understand why two receptors with apparently opposite effects are expressed in the same neuron and in the nerve terminals. The role of accessory proteins also capable of interacting with receptor-receptor heteromers in regulating the traffic and the molecular physiology of these receptors is also discussed. Overall, the knowledge of the reason why such complex networks of receptor-receptor and receptor-protein interactions occur in striatal cells is crucial to develop new strategies to combat neurological and neuropsychiatric diseases.

Heterodimeric adenosine receptors: a device to regulate neurotransmitter release.

Since 1990 it has been known that dimers are the basic functional form of nearly all G-protein-coupled receptors (GPCRs) and that homo- and heterodimerization may play a key role in correct receptor maturation and trafficking to the plasma membrane. Nevertheless, homo- and heterodimerization of GPCR has become a matter of debate especially in the search for the precise physiological meaning of this phenomenon. This article focuses on how heterodimerization of adenosine A1 and A2A receptors, which are coupled to apparently opposite signalling pathways, allows adenosine to exert a fine-tuning modulation of striatal glutamatergic neurotransmission, providing a switch mechanism by which low and high concentrations of adenosine inhibit and stimulate, respectively, glutamate release.

Síndrome de nevus azul (Blue rubber bleb nevus): reporte de un caso / Syndrome of nevus blue (blue bubber bleb nevus): report of a case

Síndrome de Blue Rubber Bleb Nevus o Síndrome de Bean, es una entidad clínica caracterizada por hemangiomas cutáneos y tumores vasculares del tracto gastrointestinal. Se describen lesiones de localización extra intestinal. Representa una causa infrecuente de hemorragia digestiva. Se presenta el caso de un paciente masculino de 19 años de edad con hemorragia digestiva, lesiones cutáneas y endoscópicas características de este síndrome

Gemcitabine/vinorelbine in metastatic breast cancer patients previously treated with anthracyclines: results of a phase II trial.

This phase II study was designed to evaluate the response rate (RR) and toxicity of gemcitabine/vinorelbine in patients with metastatic breast cancer. All patients had previously received anthracyclines. Treatment consisted of gemcitabine 1200 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8, every 3 weeks. Twenty-five patients were enrolled. Median age was 59 years (range, 33-73 years). Ten patients had received only adjuvant therapy with anthracyclines. The remaining 15 patients had received chemotherapy for metastatic disease, including taxanes in 11 cases. Four patients could not be evaluated for response. By intent-to-treat analysis, the overall RR was 44% (95% CI, 24.4%-65%). Median duration of response and median time to treatment failure were 21 and 17 weeks, respectively. The main toxicity was hematologic, with grade 3/4 neutropenia occurring in 13 patients and 1 patient developing febrile neutropenia. Two deaths from pneumonia occurred. These results reveal an encouraging activity with a reasonable toxicity profile in a patient population with an unfavorable prognosis. Our group is conducting a randomized study to compare this combination with vinorelbine alone in patients with metastatic breast cancer after failure to respond to anthracyclines and taxanes

Epithelioid angiosarcoma of the breast involving the skin: a highly aggressive neoplasm readily mistaken for mammary carcinoma.

BACKGROUND: Angiosarcomas are malignant neoplasms of endothelial cells. Angiosarcoma of the breast is a rare neoplasm that behaves in a highly malignant fashion. It must be differentiated from benign vascular proliferations and from mammary carcinoma. METHODS: We report on a 49-year-old-woman who presented with a large mass involving the left breast. RESULTS: The lesion had an erythematoviolaceous hue and livedoid pattern at the periphery. Histopathologic study showed an epithelioid malignant neoplasm, and immunohistochemical studies demonstrated that neoplastic cells expressed immunoreactivity for endothelial cell markers. CONCLUSIONS: A diagnosis of epithelioid angiosarcoma of the breast was established. The patient was treated with radical mastectomy, but she refused any other additional therapy.

Colangitis Autoinmune: reporte de un caso / Autoinmune cholangitis: reporting a case

La Colangitis Autoinmune es una enfermedad hepática de causa desconocida, con hallazgos clínicos, de laboratorio y cambios histológicos de colestasis. Algunos la consideran sinónimo de cirrosis biliar primaria con anticuerpos Antimitocondriales (AMA) negativos. Aún ni existe concenso en su definición como entidad individual. Sin embargo han sido publicados numerosos estudios con el objetivo de unificar criterios. Las pruebas de inmunohistoquímica, la determinación de la expresión de moléculas de histocompatibilidad y recientemente la identificación de anticuerpos contra la enzima anhidrasa carbónica, han facilitado la caracterización de la Colangitis Autoinmune como una enfermedad hepática autoinmune distinguible de las otras y no simplemente un subtipo de cirrosis biliar primaria con anticuerpos antimitiocondriales negativos. Se presenta la clínica, el diagnóstico, hallazgos colangiográficos e histológico y el manejo terapéutico de una paciente de 33 años con diagnóstico histológico de Colangitis Autoinmune

Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer.

The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9.

Involvement of caveolin in ligand-induced recruitment and internalization of A(1) adenosine receptor and adenosine deaminase in an epithelial cell line.

Chronic exposure of A(1) adenosine receptors (A(1)R) to A(1)R agonists leads to activation, phosphorylation, desensitization, and internalization to intracellular compartments of the receptor. Desensitization and internalization of A(1)R is modulated by adenosine deaminase (ADA), an enzyme that regulates the extracellular concentration of adenosine. ADA interacts with A(1)R on the cell surface of the smooth muscle cell line DDT1 MF-2, and both proteins are internalized following agonist stimulation of the receptor. The mechanism involved in A(1)R and ADA internalization upon agonist exposure is poorly understood in epithelial cells. In this report, we show that A(1)R and ADA interact in LLC-PK(1) epithelial cells. Exposure of LLC-PK(1) cells to A(1)R agonists induces aggregation of A(1)R and ADA on the cell surface and their translocation to intracellular compartments. Biochemical and cell biology assays were used to characterize the intracellular vesicles containing both proteins after agonist treatment. A(1)R and ADA colocalized together with the rafts marker protein caveolin. Filipin, a sterol-binding agent that disrupts rafts (small microdomains of the plasma membrane), was able to inhibit A(1)R internalization. In contrast, acid treatment of the cells, which disrupts internalization via clathrin-coated vesicles, did not inhibit agonist-stimulated A(1)R internalization. We demonstrated that A(1)R agonist N(6)-(R)-phenylisopropyl adenosine promotes the translocation of A(1)R into low-density gradient fractions containing caveolin. Furthermore, a direct interaction of the C-terminal domain of A(1)R with caveolin-1 was demonstrated by pull down experiments. These results indicate that A(1)R and ADA form a stable complex in the cell surface of LLC-PK(1) cells and that agonist-induced internalization of the A(1) adenosine receptor and ADA is mediated by clathrin-independent endocytosis.

Metabotropic glutamate 1alpha and adenosine A1 receptors assemble into functionally interacting complexes.

Recently, evidence has emerged that seven transmembrane G protein-coupled receptors may be present as homo- and heteromers in the plasma membrane. Here we describe a new molecular and functional interaction between two functionally unrelated types of G protein-coupled receptors, namely the metabotropic glutamate type 1alpha (mGlu(1alpha) receptor) and the adenosine A1 receptors in cerebellum, primary cortical neurons, and heterologous transfected cells. Co-immunoprecipitation experiments showed a close and subtype-specific interaction between mGlu(1alpha) and A1 receptors in both rat cerebellar synaptosomes and co-transfected HEK-293 cells. By using transiently transfected HEK-293 cells a synergy between mGlu(1alpha) and A1 receptors in receptor-evoked [Ca(2+)](i) signaling has been shown. In primary cultures of cortical neurons we observed a high degree of co-localization of the two receptors, and excitotoxicity experiments in these cultures also indicate that mGlu(1alpha) and A1 receptors are functionally related. Our results provide a molecular basis for adenosine/glutamate receptors cross-talk and open new perspectives for the development of novel agents to treat neuropsychiatric disorders in which abnormal glutamatergic neurotransmission is involved.

Adenosine A2B receptors behave as an alternative anchoring protein for cell surface adenosine deaminase in lymphocytes and cultured cells.

Adenosine deaminase (ADA) is an enzyme of the purine metabolism that has been largely considered to be cytosolic. Recently, it has been demonstrated that the enzyme appears on the surface of lymphocytes where it interacts with the T-cell activation antigen CD26. ADA also appears on the surface of nonlymphoid cells anchored to adenosine A1 receptors. Here it is demonstrated that cell surface ADA in ADA+/CD26- T lymphocytes anchors to adenosine receptors of the A2B subtype (A2BR). An interaction between A2BR and cell surface ADA has been demonstrated in transfected Chinese hamster ovary cells and Jurkat J32 T lymphocytes. This has been proved by coimmunoprecipitation, binding of exogenous ADA to A2BR+ cells, and coimmunolocalization. The specificity of the interaction has also been demonstrated by the lack of interaction with other members of the G protein-coupled receptor superfamily. Binding of ADA to A2BR increases the affinity of the agonist 5'-N-ethylcarboxamidoadenosine and cAMP production. This effect occurs even when ADA devoid of enzyme activity is used. Therefore, in lymphocytes, cell surface ADA, apart from degrading extracellular adenosine, regulates those actions of adenosine that are mediated via adenosine receptors of the A2B subtype.

Evidence for adenosine/dopamine receptor interactions: indications for heteromerization.

Evidence has been obtained for adenosine/dopamine interactions in the central nervous system. There exists an anatomical basis for the existence of functional interactions between adenosine A(1)R and dopamine D(1)R and between adenosine A(2A) and dopamine D(2) receptors in the same neurons. Selective A(1)R agonists affect negatively the high affinity binding of D(1) receptors. Activation of A(2A) receptors leads to a decrease in receptor affinity for dopamine agonists acting on D(2) receptors, specially of the high-affinity state. These interactions have been reproduced in cell lines and found to be of functional significance. Adenosine/dopamine interactions at the behavioral level probably reflect those found at the level of dopamine receptor binding and transduction. All these findings suggest receptor subtype-specific interactions between adenosine and dopamine receptors that may be achieved by molecular interactions (e.g., receptor heterodimerization). At the molecular level adenosine receptors can serve as a model for homomeric and heteromeric protein-protein interactions. A1R forms homodimers in membranes and also form high-order molecular structures containing also heterotrimeric G-proteins and adenosine deaminase. The occurrence of clustering also clearly suggests that G-protein- coupled receptors form high-order molecular structures, in which multimers of the receptors and probably other interacting proteins form functional complexes. In view of the occurrence of homodimers of adenosine and of dopamine receptors it is speculated that heterodimers between these receptors belonging to two different families of G-protein-coupled receptors can be formed. Evidence that A1/D1 can form heterodimers in cotransfected cells and in primary cultures of neurons has in fact been obtained. In the central nervous system direct and indirect receptor-receptor interactions via adaptor proteins participate in neurotransmission and neuromodulation and, for example, in the establishment of high neural functions such as learning and memory.

Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes.

The possible molecular basis for the previously described antagonistic interactions between adenosine A(1) receptors (A(1)R) and dopamine D(1) receptors (D(1)R) in the brain have been studied in mouse fibroblast Ltk(-) cells cotransfected with human A(1)R and D(1)R cDNAs or with human A(1)R and dopamine D(2) receptor (long-form) (D(2)R) cDNAs and in cortical neurons in culture. A(1)R and D(1)R, but not A(1)R and D(2)R, were found to coimmunoprecipitate in cotransfected fibroblasts. This selective A(1)R/D(1)R heteromerization disappeared after pretreatment with the D(1)R agonist, but not after combined pretreatment with D(1)R and A(1)R agonists. A high degree of A(1)R and D(1)R colocalization, demonstrated in double immunofluorescence experiments with confocal laser microscopy, was found in both cotransfected fibroblast cells and cortical neurons in culture. On the other hand, a low degree of A(1)R and D(2)R colocalization was observed in cotransfected fibroblasts. Pretreatment with the A(1)R agonist caused coclustering (coaggregation) of A(1)R and D(1)R, which was blocked by combined pretreatment with the D(1)R and A(1)R agonists in both fibroblast cells and in cortical neurons in culture. Combined pretreatment with D(1)R and A(1)R agonists, but not with either one alone, substantially reduced the D(1)R agonist-induced accumulation of cAMP. The A(1)R/D(1)R heteromerization may be one molecular basis for the demonstrated antagonistic modulation of A(1)R of D(1)R receptor signaling in the brain. The persistence of A(1)R/D(1)R heteromerization seems to be essential for the blockade of A(1)R agonist-induced A(1)R/D(1)R coclustering and for the desensitization of the D(1)R agonist-induced cAMP accumulation seen on combined pretreatment with D(1)R and A(1)R agonists, which indicates a potential role of A(1)R/D(1)R heteromers also in desensitization mechanisms and receptor trafficking.

The heat shock cognate protein hsc73 assembles with A(1) adenosine receptors to form functional modules in the cell membrane.

A(1) adenosine receptors (A(1)Rs) are G protein-coupled heptaspanning receptors that interact at the outer face of the plasma membrane with cell surface ecto-adenosine deaminase (ecto-ADA). By affinity chromatography the heat shock cognate protein hsc73 was identified as a cytosolic component able to interact with the third intracellular loop of the receptor. As demonstrated by surface plasmon resonance, purified A(1)Rs interact specifically with hsc73 with a dissociation constant in the nanomolar range (0.5 +/- 0.1 nM). The interaction between hsc73 and A(1)R led to a marked reduction in the binding of the ligands and prevented activation of G proteins, as deduced from (35)S-labeled guanosine-5'-O-(3-thio)triphosphate binding assays. Interestingly this effect was stronger than that exerted by guanine nucleotide analogs, which uncouple receptors from G proteins, and was completely prevented by ADA. As assessed by immunoprecipitation a high percentage of A(1)Rs in cell lysates are coupled to hsc73. A relatively high level of colocalization between A(1)R and hsc73 was detected in DDT(1)MF-2 cells by means of confocal microscopy, and no similar results were obtained for other G protein-coupled receptors. Colocalization between hsc73 and A(1)R was detected in specific regions of rat cerebellum and in the body of cortical neurons but not in dendrites or synapses. Remarkably, agonist-induced receptor internalization leads to the endocytosis of A(1)Rs by two qualitatively different vesicle types, one in which A(1)R and hsc73 colocalize and another in which hsc73 is absent. These results open the interesting possibility that signaling via G protein-coupled receptors may be regulated by heat shock proteins.

Chylopericardium of neoplastic aetiology.

Here we present the case of a 30-year-old man diagnosed with a dysgerminoma with mediastinal involvement, who developed an isolated chylopericardium during treatment. The purpose of this paper is to review the etiology, diagnosis and new approaches to the treatment of chylopericardium.

Cell surface adenosine deaminase: much more than an ectoenzyme.

During the last 10 years, adenosine deaminase (ADA), an enzyme considered to be cytosolic, has been found on the cell surface of many cells, therefore it can be considered an ectoenzyme. EctoADA, which seems to be identical to intracellular ADA and has a globular structure, does not interact with membranes but with membrane proteins. Two of these cell surface receptors for ectoADA have been identified: CD26 and A1 adenosine receptors (A1R). Apart from degradation of extracellular adenosine another functional role of ectoADA has been assigned. EctoADA is able to transmit signals when interacting with either CD26 or A1R. In this way, it acts as a co-stimulatory molecule which facilitates a variety of specific signalling events in different cell types. The heterogeneous distribution of the enzyme in the nervous system indicates that ectoADA may be a neuroregulatory molecule. On the other hand, ectoADA might act as a bridge between two different cells thus raising the possibility that it may be important for the development of the nervous system.