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Nowadays, extracellular DNA or circulating cell-free DNA is considered to be a molecule with clinical applications (diagnosis, prognosis, monitoring of treatment responses, or patient follow-up) in diverse pathologies, especially in cancer. Nevertheless, because of its molecular characteristics, it can have many other functions. This review focuses on the participation of extracellular DNA (exDNA) in fundamental processes such as cell signaling, coagulation, immunity, evolution through horizontal transfer of genetic information, and adaptive response to inflammatory processes. A deeper understanding of its role in each of these processes will allow development of better tools to monitor and control pathologies, as well as helping to generate new therapeutic options, beyond the applicability of DNA in liquid biopsy.

Pérez-Cárdenas E, Taja-Chayeb L, Trejo-Becerril C, et al. Onco Targets Ther. 2018;11:8823–8833. The authors have advised that an error during the preparation of the slide images for Figure 2C, on page 8827, led to the inadvertent duplication of features on the HV slide. All the original data was retained and the correct image for the HV treated chamber was used as a replacement. The correct Figure 2 is shown in Download Article. &nbsp

Introduction: Beyond early stages of cervical cancer (1A1, IA2, IB1, IIA1,), locally advanced disease (IB2, IIA2, IIA2, IIB, IIIA, IIIB, IIIC, IVA) and advanced (metastatic, recurrent or pe...

Introduction: There is evidence of the association of DNA methylation alterations with cancer development and progression.Areas covered: This review will briefly discuss the basis of epigenetics an...

Cancer cells have increased glycolysis and glutaminolysis. Their third feature is increased de novo lipogenesis. As such, fatty acid (FA) synthesis enzymes are over-expressed in cancer and their depletion causes antitumor effects. As fatty acid synthase (FASN) plays a pivotal role in this process, it is an attractive target for cancer therapy.This is a review of the lipogenic phenotype of cancer and how this phenomenon can be exploited for cancer therapy using inhibitors of FASN, with particular emphasis on orlistat as a repurposing drug.Disease stabilization only has been observed with a highly selective FASN inhibitor used as a single agent in clinical trials. It is too early to say whether the absence of tumor responses other than stabilization results because even full inhibition of FASN is not enough to elicit antitumor responses. The FASN inhibitor orlistat is a 'dirty' drug with target-off actions upon at least seven targets with a proven role in tumor biology. The development of orlistat formulations suited for its intravenous administration is a step ahead to shed light on the concept that drug promiscuity can or not be a virtue.

Objectives To evaluate the activity and safety of hydralazine and valproate (Transkrip) in cutaneous T-cell lymphoma (CTCL). Methods Previously untreated and progressive/refractory CTCL patients received hydralazine at 83 mg or 182 mg/day for slow and rapid acetylators respectively plus magnesium valproate at a total dose of 30 mg/Kg t.i.d daily in continuous 28-day cycles in this phase II study. The primary objective was overall response rate (ORR) measured by the modified severity weighted assessment tool (m-SWAT), secondary end-points were time to response (TTR), time to progression (TTP), duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Results Fourteen patients were enrolled (7 untreated and 7 pretreated). ORR was 71% with 50% complete and 21% partial. Two had stable disease and two progressed. At a median follow-up of 36 months (5-52), median TTR was 2 months (1-4); median DOR was 28 months (5-45); median PFS 36 and not reached for OS. There were no differences in median TTR, DOR, and PFS between treated and pretreated patients. Pruritus relieve was complete in 13 out of 14 patients. No grade 3 or 4 toxicities were observed. Conclusion The combination of hydralazine and valproate is safe, very well tolerated and effective in CTCL.

Epigenetic alterations are associated with cancer and their targeting is a promising approach for treatment of this disease. Among current epigenetic drugs, histone deacetylase (HDAC) inhibitors induce changes in gene expression that can lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range. However, it is known that VPA is a hepatotoxic drug. Therefore, the aim of this study was to design a set of VPA derivatives adding the arylamine core of the suberoylanilide hydroxamic acid (SAHA) with different substituents at its carboxyl group. These derivatives were submitted to docking simulations to select the most promising compound. The compound 2 (N-(2-hydroxyphenyl)-2-propylpentanamide) was the best candidate to be synthesized and evaluated in vitro as an anti-cancer agent against HeLa, rhabdomyosarcoma and breast cancer cell lines. Compound 2 showed a better IC50 (μM range) than VPA (mM range) on these cancer cells. And also, 2 was particularly effective on triple negative breast cancer cells. In conclusion, 2 is an example of drugs designed in silico that show biological properties against human cancer difficult to treat as triple negative breast cancer.

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m(2) as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m(2)) or cisplatin (50 mg/m(2)) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were 163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.

Aplastic anemia (AA) is a hematological disease characterized by the deficient production of blood cells. The incidence of AA worldwide is low (1-5 new cases per 10(6) individuals per year). In contrast to other countries, no current reports exist on the incidence of this disorder in Mexico. In the present study, we have determined the incidence of AA in a defined subpopulation from Mexico City during the period 1996-2000. For the purpose of this study, we focused on the experience from a single medical institution: the Mexican Institute of Social Security (IMSS), which covers around 50% of Mexico's population. The incidence of AA was determined based on the actual number of patients diagnosed with this disease at the IMSS in Mexico City in a given year and the total number of individuals registered at the IMSS in Mexico City in the same year. Considering the IMSS population as a whole, the annual incidence of AA was 3.9 new cases per 10(6) individuals per year. In the pediatric population, the annual incidence was 4.2 new cases per 10(6) individuals per year, whereas in people 15-years-old and older the incidence was 3.8 new cases per 10(6) individuals per year. These incidences were higher than those reported in most studies from the USA, Europe and Israel. Compared to the incidence in Thailand, the incidence we observed in children was considerably higher, whereas the one in adults was similar to the one in that country. The results of the present study suggest that the incidence of AA in Mexico City is one of the highest worldwide, particularly in terms of the pediatric population; however, these results must be taken with caution since this study comprises only a subpopulation from Mexico City and not the entire population. Thus, further studies including a broader population, both in Mexico City and other urban and rural areas of this country, will be necessary in order to obtain better and more complete estimates of the actual incidence of AA in Mexico.