Page 14 - Read Online

Calais da Silva et al. Systemic humoral responses during BCG treatment

during treatment. relapsing patients [Figure 3]. The increase in IL-1β
is an expected, normal physiological inflammatory
During BCG treatment, significant fast changes were the response to BCG treatment that boosts immune
expression of IL-1β, TNF-α and IL-10, which increased response in bladder tissue. However, it is well known
at the 1st and 6th week, while the expression of GNLY that prolonged exposure to inflammatory cytokines has
and Perf decreased fast at 6th week. Correlations also the potential to stimulate tumor growth through the
found between the fast changes of transcripts coding promotion of proliferation, angiogenesis, DNA damage
several pro-inflammatory cytokines and cytotoxic (due to their capacity to generate reactive oxygen
mediators further demonstrated that BCG promptly and nitrogen species), and other events favorable to
affects the systemic profile of mediators involved in metastasis. In fact, high levels of cytokines induce
[22]
both inflammatory and cytotoxic mechanisms. This reactive oxygen and nitrogen species. This may
[23]
coincides with previous studies demonstrating that explain why patients with an excessive elevation of
BCG instillation influenced local immunological activity systemic expression of IL-1β are more likely to relapse
and a systemic immune response through both sorts than patients who moderately express this cytokine.
of factors. For instance, a higher cytotoxic activity in
[21]
the PBMCs after BCG instillation has been correlated In addition, it was observed that the basal expression
to the appearance of IL-2 and IFN-γ in the serum. [21] profile of the immunomodulators also influences the
response to BCG treatment. Indeed, patients who
Interestingly, our data showed that although the were considered BCG-responders, when compared
expression of IL-1β was higher after BCG instillation, with relapsing patients, exhibited significantly less
there was a significantly lower expression of this potent expression of IFN-γ, HMOX-1 and GNLY immediately
pro-inflammatory cytokine in BCG-responders than in before the treatment at week 6 [Figure 3]. These data

Figure 3: Expression of IL-1β, IFN-γ, HMOX-1 and GNLY genes was significantly different between BCG responders and relapsing patients
at week 6. Relative mRNA levels of IL-1β, IFN-γ, HMOX-1, and GNLY were evaluated by real time PCR, as described in the Methods
section. mRNA was obtained from blood samples of BCG responder and relapsing (rel-) patients, collected before (6WBT) and 24 h after
(6WAT) BCG treatment performed 6 weeks after TURBT. Values were calculated by formula 2 -∆Ct *1,000 and infer the number of mRNA
molecules of a certain gene per 1,000 molecules of the average of the endogenous control (β-actin). Statistical significances (*P < 0.05)
refer to differences between samples from BCG responders and relapsing patients collected before (6WBT) or 24 h after (6WAT) BCG 6
weeks treatment. BCG: Bacille Calmette-Guérin; PCR: polymerase chain reaction; TURBT: transurethral resection of the bladder tumor
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ July 14, 2017 123