Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer

IntroductionBreast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk.Patients and MethodsThirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups.ResultsEstrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer.ConclusionThe decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.     

Microtubule-targeting agents in the treatment of non-small cell lung cancer: insights on new combination strategies and investigational compounds

Introduction: The management of non-small cell lung cancer (NSCLC) has been substantially improved in the last few years; it has been revolutionized by a patient-tailored approach, especially in the oncogene addicted disease, and by novel combinations containing immune checkpoint inhibitors. However, chemotherapy still represents a mainstay that persists over the decades with limited novelties. Tubulin inhibitors belong to different sub-classes of drugs that share the capability to interfere with mitosis by a direct action on the microtubule system. Among them, taxanes and vinca alkaloids still have a prominent role in clinical practice.

Areas covered: This review summarizes the mechanisms of action, current role and future directions of microtubule targeting agents; we focus on investigational agents in phase I and II clinical trials.

Expert opinion: Chemotherapy maintains a pivotal role in the treatment of NSCLC. New generation agents that have the potential to overcome the mechanisms of resistance to the available drugs may provide new therapeutic opportunities. Predictive biomarkers derived from combination strategies and phase III studies are necessary going forward.     

Poor outcomes among elderly patients hospitalized for influenza-like illness

Background and objective: Global Influenza Hospital Surveillance Network is a worldwide initiative that aims to document the burden of influenza infections among acute admissions and vaccine effectiveness in particular countries. As a partner of this platform, we aimed to determine the frequency of influenza infections among acute admissions with influenza-like illness and the outcomes of enrolled patients during the 2015–2016 influenza season in selected hospitals in Turkey.

Patients and methods: The investigators screened the hospital admission registries, chart review or available records, and screened all patients hospitalized in the previous 24–48?hours or overnight in the predefined wards or emergency room. A total of 1351 patients were screened for enrollment in five tertiary care referral hospitals in Ankara and 774 patients (57.3% of the initial screened population) were eligible for swabbing. All of the eligible patients who consented were swabbed and tested for influenza with real-time polymerase chain reaction (PCR) based methods.

Results: Overall, influenza positivity was detected in 142 patients (18.4%). The predominant influenza strain was A H1N1pdm09. Outcomes were worse among elderly patients, regardless of the presence of the influenza virus. Half of the patients over 65 years of age were admitted to the intensive care unit, while one third required any mode of mechanical ventilation and one fourth died in the hospital in that particular episode.

Conclusion: These findings can guide hospitals to plan and prepare for the influenza season. Effective influenza vaccination strategies, particularly aimed at the elderly and adults with chronic diseases, can provide an opportunity for prevention of deaths due to influenza-like illness.     

Innate Immune Recovery Predicts CD4+ T Cell Reconstitution after Hematopoietic Cell Transplantation

Innate immune cells are the first to recover after allogeneic hematopoietic cell transplantation (HCT). Nevertheless, reports of innate immune cell recovery and their relation to adaptive recovery after HCT are largely lacking. Especially predicting CD4⁺ T cell reconstitution is of clinical interest, because this parameter directly associates with survival chances after HCT. We evaluated whether innate recovery relates to CD4⁺ T cell reconstitution probability and investigated differences between innate recovery after cord blood transplantation (CBT) and bone marrow transplantation (BMT). We developed a multivariate, combined nonlinear mixed-effects model for monocytes, neutrophils, and natural killer (NK) cell recovery after transplantation. A total of 205 patients undergoing a first HCT (76 BMT, 129 CBT) between 2007 and 2016 were included. The median age was 7.3years (range, .16 to 23). Innate recovery was highly associated with CD4⁺ T cell reconstitution probability (P < .001) in multivariate analysis correcting for covariates. Monocyte (P < .001), neutrophil (P < .001), and NK cell (P < .001) recovery reached higher levels during the first 200days after CBT compared with BMT. The higher innate recovery after CBT may be explained by increased proliferation capacity (measured by Ki-67 expression) of innate cells in CB grafts compared with BM grafts (P?=?.041) and of innate cells in vivo after CBT compared with BMT (P?=?.048). At an individual level, patients with increased innate recovery after either CBT or BMT had received grafts with higher proliferating innate cells (CB; P?=?.004, BM; P?=?.01, respectively). Our findings implicate the use of early innate immune monitoring to predict the chance of CD4⁺ T cell reconstitution after HCT, with respect to higher innate recovery after CBT compared with BMT.     

Evaluation of bond strength of various margin ceramics to a zirconia ceramic

OBJECTIVE: This study evaluated the bond strengths of four different margin ceramics based on fluoroapatite and feldspath to a zirconia ceramic. METHODS: Zirconia cores (Zirconzahn) (N=28, n=7/margin ceramic group) were fabricated according to the manufacturers' instructions (diameter: 4mm; thickness: 2mm) and ultrasonically cleaned. Four different margin ceramics (thickness: 5mm) (Cerabien Zr, Noritake; Ceramco PFZ, Ceramco; e.max, Ivoclar Vivadent and Triceram, Dentaurum) were vibrated and condensed in a stainless steel mould and fired onto their zirconia cores. After trying the specimens in the mould for minor adjustments, they were again ultrasonically cleaned and embedded in PMMA. The specimens were stored in distilled water at 37 degrees C for 1 week and shear bond strength (MPa+/-S.D.) tests were performed in a universal testing machine (crosshead speed: 0.5mm/min). Failure modes were recorded under SEM. RESULTS: Significant effect of margin ceramic types were found on the bond strength values (P<0.05). The mean bond strength values of Ceramco margin ceramic to zirconia was significantly lower (25.4+/-4.5MPa) (P<0.05) than those of Cerabien (31.6+/-6.4MPa), e.max (35.9+/-8.4MPa), and Triceram margin ceramic (38.8+/-7.1MPa) systems. CONCLUSIONS: Margin ceramics, compatible with zirconia framework material tested in the present study, exhibited high bond strength values. Variations in thermal expansion coefficients might influence their bond strength values.