Docetaxel/Oxaliplatin/Capecitabine (TEX) triplet followed by continuation monotherapy in advanced gastric cancer

Introduction: Docetaxel/oxaliplatin/capecitabine (TEX) is a commonly used combination chemotherapeutic regimen in advanced gastric cancer (AGC). Application strategies in routine clinical practice are reported in this study. Materials and Methods: Patients diagnosed with AGC, receiving biweekly TEX (docetaxel - 60 mg/m (2)-D1; oxaliplatin - 85 mg/m (2)-D1, and capecitabine 500–625 mg/m (2) orally twice daily for 14 days) between July 2012 and May 2016 were retrospectively analyzed for tolerance, prognostic factors, event-free survival (EFS), and overall survival (OS). The proportion of patients continuing and terminating chemotherapy at various time-points was enumerated. Results: Overall, 208 patients were started on TEX. Median EFS was 6.34 months (95% confidence interval [CI] 5.80–6.87), and median OS was 15.31 (95% CI 12.65–17.96). Post 8 cycles of TEX, further 30 patients (14.4%) were continued on chemotherapy (docetaxel, capecitabine, or TEX) whereas 47 patients (22.6%) were on observation only, and there was a statistically significant difference in the median OS of these two groups (22.55 months vs. 14.89 months; P = 0.028). Raised serum alkaline phosphatase (SAP) levels (>100 U/L) predicted inferior survival (P = 0.006). Conclusion: TEX chemotherapy is a feasible, efficacious triplet regimen that can be used in clinical practice. SAP levels >100 U/L is a poor prognostic factor, as observed in this study. An initial “induction” such as combination chemotherapy regimen followed by monotherapy as continuation requires further evaluation

Viral complement regulators: the expert mimicking swindlers.

The complement system is a principal bastion of innate immunity designed to combat a myriad of existing as well as newly emerging pathogens. Since viruses are obligatory intracellular parasites, they are continuously exposed to host complement assault and, therefore, have imbibed various strategies to subvert it. One of them is molecular mimicry of the host complement regulators. Large DNA viruses such as pox and herpesviruses encode proteins that are structurally and functionally similar to human regulators of complement activation (RCA), a family of proteins that regulate complement. In this review, we have presented the structural and functional aspects of virally encoded RCA homologs (vRCA), in particular two highly studied vRCAs, vaccinia virus complement control protein (VCP) and Kaposi's sarcoma-associated herpesvirus complement regulator (kaposica). Importance of these evasion molecules in viral pathogenesis and their role beyond complement regulation are also discussed.

Viral mimicry of the complement system.

The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.