Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V

Fernandez, Tahía D.; Torres, Marı́a José; R-Pena, R.; Fuentes, M.S.; Robles, S. R.; Mayorga, Cristobalina; Blanca, Miguel

doi:10.1111/j.1365-2222.2005.02378.x

Cited by 17 publications

(17 citation statements)

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“…The deregulation of c-Myc confers a selective advantage on cancer cells by promoting proliferation, cell survival, and genetic instability, which can contribute to metastasis [9]. By contrast, the activation of c-Myc dramatically sensitizes cells to the apoptotic action of TRAIL by up-regulating the cell surface level of DR5 and activating DISC, thereby playing an important role in determining cellular sensitivity to TRAIL [10].…”

Section: Introductionmentioning

confidence: 99%

High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

Kim

et al. 2011

Molecular Cancer

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BackgroundTumor recurrence and metastasis develop as a result of tumors' acquisition of anti-apoptotic mechanisms and therefore, it is necessary to develop novel effective therapeutics against metastatic cancers. In this study, we showed the differential TRAIL responsiveness of human prostate adenocarcinoma PC3 and human colon carcinoma KM12 cells and their respective highly metastatic PC3-MM2 and KM12L4A sublines and investigated the mechanism underlying high susceptibility of human metastatic cancer cells to TRAIL.ResultsPC3-MM2 and KM12L4A cells with high level of c-Myc and DNA-PKcs were more susceptible to TRAIL than their poorly metastatic primary PC3 and KM12 cells, which was associated with down-regulation of c-FLIPL/S and Mcl-1 and up-regulation of the TRAIL receptor DR5 but not DR4 in both metastatic cells. Moreover, high susceptibility of these metastatic cells to TRAIL was resulted from TRAIL-induced potent activation of caspase-8, -9, and -3 in comparison with their primary cells, which led to cleavage and down-regulation of DNA-PKcs. Knockdown of c-Myc gene in TRAIL-treated PC3-MM2 cells prevented the increase of DR5 cell surface expression, caspase activation and DNA-PKcs cleavage and attenuated the apoptotic effects of TRAIL. Moreover, the suppression of DNA-PKcs level with siRNA in the cells induced the up-regulation of DR5 and active caspase-8, -9, and -3. We also found that 4,5-dimethoxy-2-nitrobenzaldehyde (DMNB), a specific inhibitor of DNA-PK, potentiated TRAIL-induced cytotoxicity and apoptosis in relatively TRAIL-insensitive PC3 and KM12 cells and therefore functioned as a TRAIL sensitizer.ConclusionThis study showed the positive relationship between c-Myc expression in highly metastatic human prostate and colon cancer cells and susceptibility to TRAIL-induced apoptosis and therefore indicated that TRAIL might be used as an effective therapeutic modality for advanced metastatic cancers overexpressing c-Myc and combination of TRAIL therapy with agent that inhibits the DNA-PKcs/Akt signaling pathway might be clinically useful for the treatment of relatively TRAIL-insensitive human cancers.

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Section: Introductionmentioning

confidence: 99%

High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

Kim

et al. 2011

Molecular Cancer

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“…Similar patterns have been detected in patients allergic to cloxacillin or penicillin V (Padial et al 2008;Blanca-Lopez et al 2009;Romano et al 1995;Terrados et al 1995). Moreover, this recognition is maintained over time independently of the BL administered (Fernandez et al 2005). This has recently been shown with clavulanic acid (Torres et al 2010a) where patients developing an IgE response to AX-clavulanic acid administration responded to BP, AX, or clavulanic acid depending on their age.…”

Section: Cross-reactivitymentioning

confidence: 51%

Hypersensitivity Reactions to Beta-lactams

Torres

Mayorga

Blanca‐López

et al. 2013

T Lymphocytes as Tools in Diagnostics and Immunotoxicology

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Beta-lactam antibiotics (BLs) are the most frequent cause of hypersensitivity reactions mediated by specific immunological mechanisms, with two main types, IgE reactions or T-cell-dependent responses. From a practical point of view, these reactions can be classified into immediate, for those appearing within 1 h after drug intake, and non-immediate, for those appearing at least 1 h after and usually within 24 h of BL administration. The clinical symptoms differ according to this classification. Urticaria and anaphylaxis are the most frequently recorded symptoms in immediate reactions and maculopapular exanthema and delayed urticaria in non-immediate reactions. Although the exact diagnostic approach differs depending on the underlying mechanism, it is based on the performance of skin testing, laboratory tests, and drug provocation tests.T cells are a key factor in all types of hypersensitivity reactions to BLs, regulating both IgE production or acting as effector cells, with a different profile of cytokine production. A Th1 pattern is observed in both CD4(+) and CD8(+) peripheral T cells in non-immediate reactions, whereas a Th2 pattern is expressed in CD4(+) T cells in immediate reactions.

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“…These initial studies changed the paradigm that patients with hypersensitivity reactions to any particular penicillin should avoid penicillins altogether. Moreover, it was demonstrated that this response did not change even after repeated doses of BP and penicillin V treatment [30]. This observation, performed in a limited number of patients, was later confirmed in a larger population including 290 patients with proven IgE-mediated hypersensitivity reactions to penicillins [31].…”

Section: Penicillin As An Alternative Treatmentmentioning

confidence: 57%

Cross-Reactivity in Betalactam Allergy: Alternative Treatments

Montañez

Ariza

Mayorga

et al. 2015

Curr Treat Options Allergy

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Opinion statementIt was originally thought that, as all betalactams share a four-member ring, they would cross-react, and so the classical recommendation was for allergic patients to avoid all betalactams. However, later studies found that some individuals selectively responded to one betalactam only and tolerated others. This was shown to be more frequent than initially thought, and this finding has led to a change from the initial recommendations of complete avoidance. Selective responses to amoxicillin are mainly due to recognition of the side chain structure, making benzylpenicillin a safe alternative. These amoxicillin-selective responders comprise up to 55 and 90 % of patients with immediate allergic reactions to amoxicillin and amoxicillin-clavulanic, respectively. Additionally, more than 85 % of penicillin-allergic patients can tolerate cephalosporins with different R 1 side chains, decreasing to 65 % if the side chain is identical. It is known that third and fourth generation cephalosporins are well tolerated by penicillin-allergic patients, probably because their chemical structures differ more from penicillins that those from the first generation. In patients with IgE-mediated allergic reactions to cephalosporins, penicillins can be an alternative treatment in up to 75 % of cases. Moreover, 40 % of patients primarily sensitized to a given cephalosporin also react to others, which might be because some cephaloporins have the same (ceftriaxone and cefotaxime) or very similar (ceftriaxone and cefuroxime) side chain structures. Finally, carbapenems and monobactams are good alternative for patients with penicillin and/or cephalosporin allergy because cross-reactivity occurs in G1 % of these cases. For all betalactams, tolerance is higher in T-cell-mediated reactions than IgE-mediated. These results show that alternative treatments for infectious disease are available to patients with allergic reactions to betalactams, from within the same group of antibiotics. Nevertheless, this general rules need to be analyzed patient by patient, and skin tests and graded challenge with the betalactam that is going to be administered are recommended. Keypoints• Patients with IgE-or T-cell-mediated allergy to betalactams can have selective reactions, specific to one betalactam with good tolerance to others, or be crossreactive, recognizing several different chemically related betalactams.• The percentage of selective reactions to the different betalactam compounds is higher than previously reported and patients should be studied in order to increase the treatment options available.

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Decrease of selective immunoglobulin E response to amoxicillin despite repeated administration of benzylpenicillin and penicillin V

Abstract: Subjects with selective IgE responses to side-chain-specific determinants seem to become negative, with no influence from subsequent administration of a closely related penicillin.

Cited by 17 publications

References 20 publications

High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

High susceptibility of metastatic cells derived from human prostate and colon cancer cells to TRAIL and sensitization of TRAIL-insensitive primary cells to TRAIL by 4,5-dimethoxy-2-nitrobenzaldehyde

Hypersensitivity Reactions to Beta-lactams

Cross-Reactivity in Betalactam Allergy: Alternative Treatments

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