Infections of Blastocystis hominis and microsporidia in cancer patients: are they opportunistic?

Chemotherapy can cause immunosuppression, which may trigger latent intestinal parasitic infections in stools to emerge. This study investigated whether intestinal parasites can emerge as opportunistic infections in breast and colorectal cancer patients (n=46 and n=15, respectively) undergoing chemotherapy treatment. Breast cancer patients were receiving a 5-fluorouracil/epirubicin/cyclophosphamide (FEC) regimen (6 chemotherapy cycles), and colorectal cancer patients were receiving either an oxaliplatin/5-fluorouracil/folinic acid (FOLFOX) regimen (12 cycles) or a 5-fluorouracil/folinic acid (Mayo) regimen (6 cycles). Patients had Blastocystis hominis and microsporidia infections that were only present during the intermediate chemotherapy cycles. Thus, cancer patients undergoing chemotherapy should be screened repeatedly for intestinal parasites, namely B. hominis and microsporidia, as they may reduce the efficacy of chemotherapy treatments.

Dual potency anti-HER2/neu and anti-EGFR anthracycline immunoconjugates in chemotherapeutic-resistant mammary carcinoma combined with cyclosporin A and verapamil P-glycoprotein inhibition.

Immunoconjugates of epirubicin were synthesized with monoclonal antibodies against the epidermal growth factor receptors, HER2/neu and EGFR, by creating a sulfhydryl-reactive epirubicin intermediate applying heterobifunctional succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), which was introduced at alpha-monoamide groups of the epirubicin carbohydrate moiety. In parallel, N-succinimidyl-S-acetylthioacetate (SATA) was used to incorporate a sulfhydryl group into immunoglobulin at the terminal amine position of -lysine amino acid residues. Eprirubicin-SMCC-SATA-IgG immunoconjugates were produced by reacting epirubicin-SMCC and SATA-IgG at appropriate molar ratios. Epirubicin-(anti-HER2/neu) and epirubicin-(anti-EGFR) had greater potency against chemotherapeutic-resistant SKBr-3 mammary carcinoma than did epirubicin at epirubicin-equivalent concentrations. Epirubicin-(anti-HER2/neu) was more potent than epirubicin-(anti-EGFR), and a synergistic level of antineoplastic activity was detected with an epirubicin immunoconjugate 50/50 combination. Competitive P-glycoprotein inhibition with cyclosporin A or verapamil enhanced the potency of the epirubicin immunoconjugate 50/50 combination. Minor levels of antineoplastic activity were detected only with an immunoglobulin 50/50 combination of anti-HER2/neu and anti-EGFR. The investigations represent a potential strategy for enhancing the selective internalization, intracellular deposition, and antineoplastic potency of chemotherapeutics in multidrug-resistant neoplasias.

Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study.

Immunotherapy is being increasingly utilized for adjuvant treatment for breast cancer (BC). We have previously described immune functions during primary therapy for BC. The present study describes immune recovery patterns during long-term, unmaintained follow-up after completion of adjuvant therapy.A group of patients with primary BC had been treated with adjuvant radio-chemotherapy (RT + CT) 5-fluorouracil, epirubicin and cyclophosphamide (FEC) (n = 21) and another group with radiotherapy (RT) (n = 20) alone. Immunological testing of NK and T-cell functions was performed initially at the end of adjuvant treatment and repeated after 2, 6 and 12 months. NK cell cytotoxicity was significantly higher (P < 0.05) at all time-points in patients than in age-matched controls and did not differ between the two treatments groups during one year observation. In contrast, lower numbers of CD4 T-cells and lower expression of CD28 on T-cells was observed particularly in RT + CT patients and did not normalize during the observation period. The numbers of T(reg) cells (CD4(+)CD25(high)) were low in the RT + CT group during follow-up, as well as expression of TCRxi, Zap70, p56(lck), P59(fyn) and PI3 k in CD4(+) cells. In contrast, expression of intracellular cytokines (IFN-gamma, IL-2, IL-4) in CD4 and CD8 T cells were significantly higher in RT + CT patients than in the RT group and the difference increased during follow-up. In conclusion, NK-cell cytotoxicity increased during unmaintained long-term follow-up whereas CD4 and regulatory T cells as well as signal transduction molecules remained low following adjuvant radio-chemotherapy.

Search of anti-adriamycin antibodies in serum of cancer patients under chemotherapic treatment.

The exposure to DNA reactive carcinogens is known to elicit a specific humoral immunological response, with the production of antibodies towards the carcinogen adducts. In analogy to chemical carcinogens, any chemotherapic, like Adriamycin, undergoes the same adduct formation, and for this reason could elicit specific antibodies. In this case we can suppose that an eventual immunological response could influence the efficacy of chemotherapy. The aim of this study was to verify if adriamycin adducted to DNA or transport proteins can elicit an immunological response of specific anti-adriamycin (ADM) antibodies in sera of 43 cancer patients treated with the drug. No specific antibodies were detected in these individuals. The lack of anti-adriamycin antibodies suggests that the therapeutic exposure to the drug does not elicit a specific immunological response.

Production and characterization of a monoclonal antibody against epirubicin.

Epirubicin is an anthracyclinic antibiotic that has been increasingly used in the treatment of a variety of malignancies. A hybridoma producing monoclonal antibody (MAb) against the drug was obtained by cell fusion. The MAb is of the IgM isotype and has an affinity constant of 1.4 x 10(-7) M. Inhibition analysis showed that the antibody recognizes an epitope related to the C 4'-hydroxyl group in the amino sugar moiety, distinguishing epirubicin from the closely related doxorubicin. Since the precise mechanism of anthracycline action as well as its immunomodulating effects are still under scrutiny, powerful tools for their study are clearly needed. Moreover, this MAb can be useful in monitoring the levels of epirubicin in treated patients, as well as for the construction of bispecific antibodies in tumor-targeting immunotherapy.