Factors that influence the antiemetic activity of metoclopramide to cisplatin based chemotherapy.

Some clinical parameters play a role in developing effective antiemetic therapy. In the present study, 310 patients entered and 301 were evaluable. They received cisplatin based combination chemotherapy (100 mg/m2), with antiemetic therapy based in metoclopramide, at a standard dose and schedule (2 mg/kg in 5 doses).

Somatic hypermutation of immunoglobulin variable region genes: focus on follicular lymphoma and multiple myeloma.

Analysis of the rearranged immunoglobulin variable region gene hypermutation has provided important information concerning the clonal history and ontogenetic origin of various B-cell lymphoproliferative disorders. Under the selective pressure of antigen, mutational events in immunoglobulin genes will fine tune survival of B-cell clones bearing immunoglobulin with high affinity for antigen. Our studies aimed at analyzing neoplastic disorders originating from germinal and post-germinal center B-cells: follicular lymphoma and multiple myeloma, respectively.

Clinical symptomatology of coronary artery disease and results of exercise thallium scintigraphy: gender-related differences.

Exercise thallium stress test is the mainstay of the noninvasive assessment of patients with symptomatology suggestive of coronary artery disease. The diagnostic accuracy of thallium scintigraphy as a screening test for coronary artery disease in women as compared to men, however, remains controversial. In order to determine whether gender-related differences in the detection of coronary artery disease using exercise thallium scintigraphy are demonstrable in all age groups, we analyzed the exercise thallium results in 335 outpatients (189 male, 146 female), who were referred by their primary physicians to our institution for evaluation of clinically suspected coronary artery disease.

t(14;18) chromosomal translocation in follicular lymphoma: an event occurring with almost equal frequency both at the D to J(H) and at later stages in the rearrangement process of the immunoglobulin heavy chain gene locus.

bcl-2/IgH fusion is considered a genetic error which occurs at the diversity (D) to joining (J(H)) stage of the gene rearrangement process in the immunoglobulin heavy chain (IgH) gene locus. Translocations of the bcl-2 protooncogene to the IgH locus at ontogenetically later IgH gene rearrangements are thought to represent exceptions. In the present study we analysed the junctional nucleotide sequence of 18 bcl-2/IgH fusion genes identifiable by polymerase chain reaction performed on DNA extracted from diagnostic lymph node tissue of 14 follicular lymphoma patients.

Chemotherapy of non small cell lung cancer. A prospectively randomized study of cisplatin-etoposide versus cisplatin-mitomycin-vinblastine.

Based on preclinical studies showing synergism between cisplatin and etoposide, we randomized patients with non small cell lung cancer (NSCLC) to receive either the above combination (cisplatin 100 mg/m2 day 1, etoposide 130 mg/m2 days 1-3) or the combination of cisplatin-mitomycin-c and vinca drugs (MVP) (cisplatin 100 mg/m2, vinblastine 6 mg/m2, mitomycin 10 mg/m2 day 1), a regimen with a steady response rate. Partial responses were achieved in 12/44 (27%) of the cisplatin-etoposide group and in 11/43 (26%) of the MVR group. No difference in median survival could be demonstrated between the two groups (36 weeks versus 38 weeks).

A feasibility study of 1-h paclitaxel infusion in patients with solid tumors.

The optimal schedule for paclitaxel administration has not yet been determined. This phase I/II study was carried out to evaluate the safety of paclitaxel administration by 1-h infusion in the outpatient setting. A total of 43 patients with advanced pretreated malignancies (18 breast, 18 ovarian, and 7 non-small-cell lung cancers) received at least 2 cycles of paclitaxel given at 175 mg/ m2 in a single dose by 1-h i.

Follicular lymphoma immunoglobulin kappa light chains are affected by the antigen selection process, but to a lesser degree than their partner heavy chains.

Follicular lymphoma cells carry surface immunoglobulin whose heavy chain variable (VH) regions exhibit considerable divergence from the aminoacid sequence predicted by the germline nucleotide sequence as a result of the somatic hypermutation process. The present study examined the extent of somatic hypermutation in follicular lymphoma kappa light chain variable region (V kappa) genes about which the available data is limited. DNA extracted from fresh frozen lymph node tissue of 14 patients with follicular lymphoma at diagnosis was subjected to polymerase chain reaction (PCR) amplification aimed at detecting clonal VH and VL (L: light chain) gene rearrangements.

Time-limited efficacy of pacing electrodes following open heart surgery.

Temporary epicardial pacing electrodes have been utilised since the 1960s in the postoperative management of cardiac surgical patients, both as a diagnostic tool and therapeutic intervention. To determine the efficacy of the epicardial pacing wires over time after open heart surgery, 30 patients (20M/10F) who underwent coronary artery bypass surgery, were evaluated by standard 12-lead EKG, atrial electrogram, and atrial and ventricular pacing thresholds immediately after surgery and on postoperative day 5. Both atrial and ventricular pacing thresholds were significantly increased on postoperative day 5 as compared to baseline.

5-Fluorouracil, epirubicin, and mitomycin C versus 5-fluorouracil, epirubicin, mitomycin C, and leucovorin in advanced gastric carcinoma. A randomized trial.

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based on these data, we performed a randomized trial with 5FU, epirubicin (EPI), mitomycin C(MMC) with/ without LV in advanced gastric cancer (AGC). The purpose of our study was to investigate if the addition of LV improved the response rate of the combination 5FU EPI, MMC (FEM) over FEM.

Evidence for immunoglobulin heavy chain variable region gene replacement in a patient with B cell chronic lymphocytic leukemia.

Immunoglobulin heavy chain variable (V) gene replacement is an unusual recombinatorial event characterized by rearrangement of a germline V gene to a preformed VDJ gene complex. This phenomenon has occasionally been implicated in the emergence of clonal subpopulations during the course of acute lymphoblastic leukemia; it has also been found in murine precursor B cell lines. V gene replacement has never been described in lymphoproliferative disorders corresponding to more differentiated stages of B cell ontogeny.

Analysis of the kappa light chain variable region in multiple myeloma.

The study of immunoglobulin heavy chain gene rearrangements in multiple myeloma has revealed extensive divergence from the germline sequences, but no intraclonal diversity with disease evolution. Our study investigated the state of the rearranged kappa light chain variable region (V kappa) gene segments as well as abortive V kappa family gene usage in cases of multiple myeloma expressing lambda light chain. We studied 11 cases of kappa and five cases of lambda light chain-expressing multiple myeloma.

A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer.

Combination chemotherapy (CT) has, in some groups of patients with gastric cancer (GC), who are at a high risk for relapse, resulted in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting. Based on the above data, we studied adjuvant CT with FEM (5-fluorouracil (5-FU), epirubicin, mitomycin C) in a randomized study of patients with completely resected stage III GC and patients with stages T1-3 with a low histologic grade. CT was started 2-3 weeks after surgery.

Monomorphic right ventricular tachycardia in a patient with mitral valve prolapse.

A patient with mitral valve prolapse and symptomatic ventricular ectopy underwent an electrophysiological study during which a sustained monomorphic ventricular tachycardia with a left bundle branch block/right axis deviation morphology was induced. This morphology was replicated by pace mapping at the right ventricular outflow tract. To the best of our knowledge, this finding has not been previously described and suggests that the association between ventricular arrhythmias and mitral valve prolapse may not necessarily be causal.

Biochemical modulation of fluorouracil: comparison of methotrexate, folinic acid, and fluorouracil versus folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial.

Recent advances in biochemical pharmacology have revealed the basis for the biological modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and folinic acid (FA). Sequential use of MTX given 24 h prior to 5-FU has resulted in enhanced cell kill in vitro and in vivo. In addition, administration of FA prior to 5-FU has led to potentiation of 5-FU action by stabilization of the ternary complex of thymidine synthase.

5-Fluorouracil, folinic acid and cisplatin in advanced colorectal cancer: a pilot study.

The combination of 5-fluorouracil (5-FU) and folinic acid (FA) has demonstrated activity in colorectal cancer (CC). Cisplatin is reported to have synergistic activity with 5-FU. We examined the combination FA + 5-FU + cisplatin in patients who had previously received chemotherapy with FA + 5-FU and relapsed.

Anti-chelate antibodies after intraperitoneal yttrium-90-labeled monoclonal antibody immunoconjugates for ovarian cancer therapy.

Unlabelled: The development of stable chelating agents for metal isotopes (e.g., 90Y) such as CITC-DTPA, a benzyl-analog of DTPA, allowed us to evaluate the efficacy of 90Y-labeled HMFG1 MAb administered intraperitoneally in patients with ovarian cancer.

Activation of cellular immunity after intracavitary monoclonal antibody therapy of ovarian cancer.

Background: Murine monoclonal antibodies (MoAbs) are now used for targeted tumor therapy. A major obstacle in their successful application is the development of a humoral antiglobulin response, which limits the use of repeated cycles of therapy. The cellular aspects of that response are not well understood.

Pharmacokinetics and toxicity of an yttrium-90-CITC-DTPA-HMFG1 radioimmunoconjugate for intraperitoneal radioimmunotherapy of ovarian cancer.

Background: The intracavitary route for the administration of monoclonal antibodies is used in a variety of locally spreading cancers. The authors have been treating patients with ovarian cancer in Phase I and II studies assessing toxicity and response to improved radioimmunoconjugates.

Methods: Nineteen patients, 34-65 years of age, were treated with a new radioimmunoconjugate, 90Y-CITC-DTPA-HMFG1, instilled in the peritoneal cavity after second-look laparoscopy.

Targeting of tumours with murine and reshaped human monoclonal antibodies against placental alkaline phosphatase: immunolocalisation, pharmacokinetics and immune response.

Anti-tumour monoclonal murine and humanised (reshaped human) antibodies (H17E2 and Hu2PLAP, respectively) against placental alkaline phosphatase (PLAP), radioactively labelled with indium-111 (111In) and iodine-123 (123I), were evaluated for their ability to localise mainly testicular and ovarian tumours in sequential pilot studies of the Hammersmith Oncology Group. 33 patients with active primary and/or metastatic testicular cancer were studied with the [111In]- or [123I]H17E2 antibody. 8 patients with testicular cancer were studied with the same antibody after being rendered free of disease after induction chemotherapy and surgical resection of residual tumour.

Review: advances in monoclonal antibody tumour targeting.

Since the breakthrough in producing monoclonal antibodies was achieved, this new tool has opened up numerous avenues in basic science and clinical investigation. In the area of oncology, monoclonal antibodies were initially seen as offering new hopes of a cure and many investigations in the last decade therefore focused on applying these reagents in tumour diagnosis and therapy. The results to date have been less encouraging and have served as a basis for understanding current limitations in the application of monoclonal antibodies and designing future strategies to overcome these problems.

Effects of phorbol esters and cytokines (interleukin-2,-4, and -6) on the proliferation and surface phenotype of Epstein-Barr virus immortalised human B lymphocytes.

Epstein-Barr virus (EBV)-induced in vitro infection of peripheral blood mononuclear cells (PBMCs) leads to a polyclonal proliferation and immortalisation of B lymphocytes. In the present study we determined the effects of three different cytokines, interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-6 (IL-6), and the tumour promoting phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on EBV-immortalised B lymphocytes. These factors have known activities on normal B cells.

Development of humoral immune responses against a macrocyclic chelating agent (DOTA) in cancer patients receiving radioimmunoconjugates for imaging and therapy.

The development of stable immunoconjugates by the advent of macrocyclic metal chelating agents (DOTA) has enabled us to study the ability of 111In-DOTA-labeled monoclonal antibodies to detect tumor lesions in a pilot radioimmunolocalization study, as well as to evaluate the kinetics, toxicity, and efficacy of i.p. administered 90Y-DOTA-labeled murine monoclonal antibody in a Phase I/II clinical trial of advanced ovarian cancer.

Tumour localisation with a radioactively labelled reshaped human monoclonal antibody.

A genetically reshaped human IgG1 monoclonal antibody (Hu2PLAP) with anti-tumour specificity, was radiolabelled with Indium-111 by chelation with a new macrocyclic compound (DOTA) which allows the production of stable radioimmunoconjugates for in vivo application. This was used to image seven patients with malignant disease, of whom two had been previously exposed to mouse monoclonal antibodies and had developed human anti-mouse antibodies (HAMA). Successful tumour localisation was seen in the four patients with active disease and antigen positive tumours.