Outcomes of cytoreductive operations for peritoneal carcinomatosis with or without liver cytoreduction in patients with small bowel neuroendocrine tumors.

BACKGROUND: This study determines how much cytoreduction for small bowel neuroendocrine tumors with peritoneal carcinomatosis and liver metastases can be achieved and the corresponding survival benefits of different levels of clearance. METHODS: Records of patients with small bowel neuroendocrine tumors with peritoneal carcinomatosis were reviewed and scored using the Lyon Stage system. Kaplan-Meier survival was calculated and compared by log-rank analysis. RESULTS: Among 323 patients with small bowel neuroendocrine tumors identified, 98 (30%) had peritoneal carcinomatosis. At laparotomy, 82% had Lyon Stage ≥3 compared with 78% who had Lyon Stage ≤2 after debulking (P < .00001). Median overall survival for Lyon Stage = 0 was 132 months and 51 months for Lyon Stage ≥1 (P = .026). For incomplete clearance, overall survival was 76 months for Lyon Stage ≤1 compared with 32 months for Lyon Stage ≥3 (P = .037). Seventy-nine (81%) patients had liver metastases, and 57 underwent >70% liver metastases cytoreduction. Overall survival was 76 months for Lyon Stage ≤1 and >70% liver metastases cytoreduction, 38.5 months for Lyon Stage ≥3 and >70% liver metastases cytoreduction, 22 months for Lyon Stage ≤1 and liver metastases not cytoreduced, and 20 months for Lyon Stage ≥3 and liver metastases not cytoreduced (P = .018). CONCLUSION: A majority of patients with peritoneal carcinomatosis from small bowel neuroendocrine tumors can be cytoreduced. Best survival times are seen with complete clearance; however, there are improved survival times for Lyon Stage ≤1. In patients with liver metastases, best survival after cytoreduction is seen when both Lyon Stage ≤1 and liver metastases >70% are achieved.

Evidence of heterogeneity in the antibody response against the platelet antigen 3a; recognition of an 11-mer peptide carrying the HPA-3a polymorphic determinant.

BACKGROUND: The immune processes involved in the development of alloantibodies against the human platelet antigens in alloimmune disorders remain unclear. Antibody recognition of the platelet antigens on their respective platelet glycoproteins has been shown to be dependent on glycoprotein conformation. Furthermore, the post-translational modification of glycoproteins adds complexity to the alloantigenic determinants. METHODS: Nine anti-HPA-3a sera along with several control sera were tested for reactivity to an 11-mer peptide straddling the HPA-3a/b polymorphism. Sera found to specifically recognize the 3a peptide were further assessed by platelet pre-exposure and immunoblotting. RESULTS: Three of the nine antisera were found to specifically recognize an 11-mer synthetic 3a peptide by ELISA. Further analysis of all anti-HPA-3a sera by Western blot showed that only those reactive to the 3a peptide were able to bind both reduced and non-reduced GPIIb. CONCLUSION: The results presented in this study provide the first known evidence for the identification of an antibody population capable of recognizing a linear and non-glycosylated form of the HPA-3a epitope.

A new chloroquinolinyl chalcone derivative as inhibitor of inflammatory and immune response in mice and rats.

The synthetic chalcone derivative 1-(2,4-dichlorophenyl)-3-(3-(6,7-dimethoxy-2-chloroquinolinyl))-2-propen-1-one (ClDQ) was evaluated for its anti-inflammatory, analgesic and immunomodulatory efficacy in-vitro and in-vivo. ClDQ concentration-dependently inhibited the production of nitric oxide (NO) (IC50 4.3 microM) and prostaglandin E(2) (PGE(2)) (IC50 1.8 microM) in RAW 264.7 macrophages stimulated with lipopolysaccharide. Human mononuclear cell proliferation was significantly inhibited by 10 microM ClDQ. Oral administration of ClDQ (10-30 mg kg(-1)) in the 24-h zymosan-stimulated mouse air-pouch model produced a dose-dependent reduction of cell migration as well as NO and PGE(2) levels in exudates. ClDQ (20 mg kg(-1), p.o.) inhibited ear swelling and leucocyte infiltration in the delayed-type hypersensitivity response to 2,4-dinitrofluorobenzene in mice. In the rat adjuvant-arthritis model, this compound reduced joint inflammation as well as PGE(2) and cytokine levels. In addition, ClDQ displayed analgesic effects in the phenylbenzoquinone-induced abdominal constriction model in mice and in the late phase of the nociceptive response to formalin. Our findings indicated the potential interest of ClDQ in the modulation of some immune and inflammatory conditions.

1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one, a chalcone derivative with analgesic, anti-inflammatory and immunomodulatory properties.

OBJECTIVE AND DESIGN: The synthetic chalcone derivative 1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one (TQ) was evaluated for its immunomodulatory and anti-inflammatory efficacy in vitro and in vivo. MATERIAL AND SUBJECTS: Human neutrophils and lymphocytes from healthy volunteers and RAW 264.7 murine macrophages. Swiss mice and Lewis rats were randomly divided into groups of six animals. TREATMENT: TQ was orally administered in all in vivo assays (10-30 mg/kg). METHODS: Elastase, superoxide and LTB(4) release were assayed in human neutrophils, NO/PGE(2) production and NF-kappaB activation in RAW 264.7, and (3)H thymidine incorporation in human lymphocytes. Zymosan-stimulated air pouches, DNFB-DTH, PBQ-induced writhings and formalin-induced pain were assayed in mice. Adjuvant-induced arthritis was tested in rats. Dunnett's t-test was employed for statistical analysis. RESULTS: Human T-cell proliferation, neutrophil functions and NO/PGE(2) production in murine macrophages were inhibited by TQ (IC(50) in the microM range), which showed anti-inflammatory, immunomodulatory and analgesic effects. CONCLUSIONS: Our findings indicate the potential interest of TQ in the modulation of some immune and inflammatory responses probably by NF-kappaB inhibition.

Mechanical properties of a self-assembling oligopeptide matrix.

We have begun studies of a novel type of biomaterial derived from a recently-discovered class of ionic self-complementary oligopeptides. These short peptides (typically 8, 16, 24, or 32 amino acid residues with internally-repeating sequences) self-assemble in aqueous salt solution into three-dimensional matrices capable of favorable interactions with cells, and offer promise for useful bioengineering design based on rational changes in sequence. In this paper we present preliminary results on mechanical properties, combining experimental and theoretical approaches, of one particular example of these peptide materials, EFK8. The static elastic modulus was measured using an apparatus designed to allow sample fabrication and mechanical testing in the same system with the sample in aqueous solution. The material microstructure was examined by SEM and the measurements interpreted with the aid of a model for cellular solids. Values for the elastic modulus increased from 1.59 +/- 0.06 to 14.7 +/- 1.0 kPa for peptide concentrations increasing from 2.7 to 10 mg ml-1. SEM photographs showed the microstructure to consist of a relatively homogeneous lattice with fiber thickness of 10-30 nm independent of peptide concentration, but with fiber density increasing with peptide concentration. This behavior is consistent with scaling predictions from the cellular solids model and yields an estimate for the individual fiber elastic modulus in the range of 1-20 MPa. We therefore have provided some initial physical principles for guiding improvement of the mechanical properties of these new materials.