Specifics of diagnosis and treatment in synchronous colorectal cancers (SCC).

INTRODUCTION: SCC have an incidence of 1,8% up to 12,4% and could have more simultaneous localizations. MATERIAL AND METHOD: Between January 2004 and January 2011, 214 patients with CRC have been operated on in our ward; from those, eight patients had multiple colorectal neoplasms. RESULTS: The majority of SCC (six cases) was hospitalized under emergency status, with incomplete or complete bowel obstruction through colonic obstructive tumour. The favourite localizations were on the sigmoid (six tumours) and the transverse colon (four tumours). The diagnosis was preoperatively assessed in three cases by colonoscopy and barium enema, intraoperative in four cases, postoperative in one case. Curative operations were performed in five cases and palliative operations in three. Immediate postsurgical evolution was good, long time evolution was marked by the complications of the primary disease. Out of five patients that were long term monitored, three have a five year survival, one has survived for three years and one deceased within a nine month period after surgery, with multiple metastases. CONCLUSIONS: Preoperative diagnosis of synchronous lesions can be difficult (emergency hospitalized patient, incomplete bowel preparation, bowel obstruction or intestinal bleeding) and the colonoscopy exam can be incomplete. Rigorous intraoperative colonic examination is necessary in order to diagnose synchronous lesions and avoid surgical reintervention.

A T-cell-selective interleukin 2 mutein exhibits potent antitumor activity and is well tolerated in vivo.

Human interleukin 2 (IL-2; Proleukin) is an approved therapeutic for advanced-stage metastatic cancer; however, its use is restricted because of severe systemic toxicity. Its function as a central mediator of T-cell activation may contribute to its efficacy for cancer therapy. However, activation of natural killer (NK) cells by therapeutically administered IL-2 may mediate toxicity. Here we have used targeted mutagenesis of human IL-2 to generate a mutein with approximately 3,000-fold in vitro selectivity for T cells over NK cells relative to wild-type IL-2. We compared the variant, termed BAY 50-4798, with human IL-2 (Proleukin) in a therapeutic dosing regimen in chimpanzees, and found that although the T-cell mobilization and activation properties of BAY 50-4798 were comparable to human IL-2, BAY 50-4798 was better tolerated in the chimpanzee. BAY 50-4798 was also shown to inhibit metastasis in a mouse tumor model. These results indicate that BAY 50-4798 may exhibit a greater therapeutic index than IL-2 in humans in the treatment of cancer and AIDS.

Further studies on the determinant recognized by naturally-occurring murine autoantibodies reacting with bromelain-treated erythrocytes.

Radioimmunoassays (RIA) have confirmed previous studies that trimethylammonium (TMA) or its derivatives constitute part of the determinant recognized by naturally-occurring antibodies (NOA) with the ability to interact with bromelain-treated mouse erythrocytes (BrMRBC). Further studies on this determinant revealed its presence on erythrocytes from several species in addition to mice. In most cases (except in chickens) the determinant was cryptic and could be exposed only after proteolytic treatment of the erythrocytes. The determinant was also found on certain murine lymphoma cells. We also found that bromelain was not the only enzyme that could be used to expose the determinant. Papain, but not trypsin, was able to unmask the determinant on mouse erythrocytes. Rabbit antibodies directed against the idiotypes of four different monoclonal BrMRBC-binding NOA were prepared. Direct RIA assays and inhibition assays showed that the different monoclonal BrMRBC-binding NOA shared a common idiotype specific to such antibodies. The common idiotype was detected in the serum from several mouse strains and in wild mice.

Binding characteristics of human serum amyloid P component.

Serum amyloid P component (SAP), a normal human plasma glycoprotein, was found in a solid phase ELISA to have Ca2+-dependent binding for keyhole limpet haemocyanin (KLH), pectic acid, trinitrophenylated (TNP) macromolecules, and plastic surfaces. The binding to TNP-KLH was used to develop a sensitive ELISA. The binding of SAP to the ligands mentioned was inhibited by EDTA, KLH, pectic acid, TNP-conjugated macromolecules (bovine serum albumin, polyacrylhydrazide), and p-nitrophenylarsonic acid. Underivatized and DNP-conjugated macromolecules did not inhibit the SAP binding; arsenilic acid, picric acid, and dinitrophenyl were weak inhibitors. SAP bound to TNP-agarose was eluated by either EDTA or p-nitrophenylarsonic acid. Thus, a unique region of SAP is responsible for the polyspecific binding. We suggest that the polyspecific binding of SAP takes place through a Ca2+ bridge: half of the metal coordination sphere is occupied by SAP, with the other half available to interact with metal ligand.

Relationship between choline derivatives and mouse erythrocyte membrane antigens revealed by mouse monoclonal antibodies. I. Anticholine activity of anti-mouse erythrocyte monoclonal antibodies.

Different clones of mouse hybridomas, derived from the fusion of unstimulated mouse peritoneal cells with mouse myeloma cells, producing IgM monoclonal antibodies directed against the membrane of bromelain-treated mouse erythrocytes (MRBC(Br)) have been previously established. We have recently shown that one of these hybridomas produce, in ascites, antibodies cross-reacting with phosphorylcholine derivatives (trimethylammonium (TMA) derivatives). In this work the cross-reactivity for TMA derivatives of the monoclonal antibodies produced by 4 anti-MRBC(Br) hybridomas have been studied at the cell level (plaque-forming cells). Phosphorylcholine, choline bromide and p-aminophenyl-trimethylammonium were found to be potent specific inhibitors of plaque formation (anti MRBC(Br)). The hemolytic activities of ascites and tissue culture supernatants were studied and their inhibition by TMA derivatives was determined. Immunoglobulins from ascites purified on TMA immunoadsorbent column were analyzed by two-dimensional gel electrophoresis, their spectrotype was compared to the spectrotype of immunoglobulins from tissue culture supernatants from the same hybridoma radioactively tagged by internal incorporation of [14C]leucine. It could be shown without ambiguity that the PTMA column retained an IgM with the same characteristics as the IgM secreted in vitro.

The participation of trimethylammonium in the mouse erythrocyte epitope recognized by monoclonal autoantibodies.

Monoclonal IgM anti-erythrocyte autoantibody produced by a NZB-derived hybridoma has been found to react with trimethylammonium-containing compounds. Such compounds are able to prevent the lysis of bromelain-treated mouse erythrocytes (BrMRBC) by those autoantibodies. Using a column of insolubilized betaine hydrazine (BH) the monoclonal anti-erythrocyte antibody has been specifically retained. Elution of this antibody was accomplished by 0.15 M choline (Ch).