Efficacy and Safety of Nimotuzumab Plus Radiotherapy With or Without Cisplatin-Based Chemotherapy in an Elderly Patient Subgroup (Aged 60 and Older) With Nasopharyngeal Carcinoma

OBJECTIVE: This study was conducted to assess the efficacy and safety of nimotuzumab combined with radiotherapy (RT) in elderly patients with nasopharyngeal carcinoma. MATERIALS AND METHODS: The clinical data of 75 nasopharyngeal carcinoma patients, who were initially treated with nimotuzumab combined with RT, were collected and retrospectively reviewed from December 2008 to April 2014. They were aged 60 to 81 years (median 64 years). The distribution of disease was stage II in 10 (13.3%), stage III in 33 (44.0%), and stage IV in 32 (42.7%). Among these patients, 59 cases received cisplatin-based chemotherapy. Survival outcomes and treatment toxicity were analyzed using IBM SPSS 19.0 software. RESULTS: With a median follow-up of 45 months (range, 13-78 months), the estimated 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression failure-free survival (PFS), and overall survival (OS) rates were 95.6%, 95.5%, 98.6%, 89.7%, and 89.2%, respectively. In the subgroup, 3-year OS rate in the patients with concurrent chemotherapy was 90.5% and 77.4% in patients without concurrent chemotherapy (Log-Rank = 1.795, P = .180). Univariate analysis showed that T stage and clinical stage were correlated with OS. Multivariate analysis indicated that age, T stage and tumor response at the end of treatment were independent prognosticators. Nine patients experienced grade 3 to 4 acute mucositis and 26 patients experienced grade 3-4 leukocytopenia, with no cases of skin rash and infusion reaction. Twelve patients developed mild liver function damage. No serious gastrointestinal or renal toxicities were observed. CONCLUSION: The efficacy of combined nimotuzumab with RT in elderly NPC patients was encouraging and the toxicities were accepted. In addition, nimotuzumab provides a better option for elderly patients who cannot be tolerate chemotherapy.     

In Situ Determination of Manganese(II) Speciation in Deinococcus radiodurans by High Magnetic Field EPR: DETECTION OF HIGH LEVELS OF Mn(II) BOUND TO PROTEINS*

High magnetic field high frequency electron paramagnetic resonance techniques were used to measure in situ Mn(II) speciation in Deinococcus radiodurans, a radiation-resistant bacteria capable of accumulating high concentrations of Mn(II). It was possible to identify and quantify the evolution of Mn(II) species in intact cells at various stages of growth. Aside from water, 95-GHz high field electron nuclear double resonance showed that the Mn(II) ions are bound to histidines and phosphate groups, mostly from fructose-1,6-bisphosphate but also inorganic phosphates and nucleotides. During stationary growth phase, 285-GHz continuous wave EPR measurements showed that histidine is the most common ligand to Mn(II) and that significant amounts of cellular Mn(II) in D. radiodurans are bound to peptides and proteins. As much as 40% of the total Mn(II) was in manganese superoxide dismutase, and it is this protein and not smaller manganese complexes, as has been suggested recently, that is probably the primary defense against superoxide.     

Inhibition of Cell Growth by Overexpression of Manganese Superoxide Dismutase (MnSOD) in Human Pancreatic Carcinoma

Manganese superoxide dismutase (MnSOD) levels have been found to be low in human pancreatic cancer [Pancreas26, (2003), 23] and human pancreatic cancer cell lines [Cancer Res.63, (2003), 1297] when compared to normal human pancreas. We hypothesized that stable overexpression of pancreatic cancer cells with MnSOD cDNA would alter the malignant phenotype. MIA PaCa-2 cells were stably transfected with a pcDNA3 plasmid containing sense human MnSOD cDNA or containing no MnSOD insert by using the lipofectAMINE method. G418-resistant colonies were isolated, grown and maintained. Overexpression of MnSOD was confirmed in two selected clones with a 2-4-fold increase in MnSOD immunoreactive protein. Compared with the parental and neo control cells, the MnSOD-overexpressing clones had decreased growth rates, growth in soft agar and plating efficiency in vitro, while in vivo, the MnSOD-overexpressing clones had slower growth in nude mice. These results suggest that MnSOD may be a tumor suppressor gene in human pancreatic cancer.     

Challenges of Radiation Oncology in Spain Today

The increasing cost of health care delivery, coupled with reduced investments and budget cuts in European health care systems, has had a severe negative impact on health care delivery in Spain. This reduction in spending has had particularly negative effects on specialties that are heavily reliant on large capital investments to purchase the latest technologies needed to deliver optimal radiotherapy treatments. The Spanish Society of Radiation Oncology has been proactively working to mitigate the negative impact of budget cuts in Spain. In this paper, the authors describe a variety of solutions and proposals to overcome these challenges.     

Advances and future of Radiation Oncology

Aim

Review of recent advances and vision for future developments in clinical practice of Radiation Oncology.

Background

There have been substantial research and technological developments in Radiation Oncology over the past 40 years.

Materials and methods

The relevant literature was reviewed and the authors offer their perspective on future opportunities for advancement in Radiation Oncology.

Conclusions

Significant innovative technological developments have been introduced in the practice of Radiation Oncology, with more precise target delineation and tracking and three dimensional treatment planning, optimal delivery of radiation therapy to the target and lower doses to surrounding Organs at Risk. This dose optimization and adaptive therapy have enhanced the role of Radiation Therapy to more effectively treat patients with cancer. Further creativity and refinements will continue to advance the field into new applications of ionizing radiations in cancer therapy.     

Birds perching on bushes: Networks to visualize conflicting phylogenetic signals during early avian radiation

Hybridization is increasingly seen as an important source of adaptive genetic variation and biotic diversity. Recent phylogenetic studies on the early evolution of birds suggest that the early diversification of neoavian orders perhaps involved a period of extensive hybridization or incomplete lineage sorting. Phylogenetic error, saturation, long-branch attraction, and convergence make it difficult to detect ancient hybridization events and differentiate them from incomplete lineage sorting using sequence data. We used recently published retroposon marker data to visualize the early radiation of Neoaves within a phylogenetic network approach, and found that the most basal neoavian taxa indeed show a complex pattern of reticulated relationships. Moreover, the reticulation levels of different parts of the network are consistent with the insertion pattern of the retroposon elements. The use of network-based analyses on homoplasy-free data shows true conflicting signals and the taxa involved that are not represented in trees.     

Effects of ionizing radiation on mitochondria

The current concept of radiobiology posits that damage to the DNA in the cell nucleus is the primary cause for the detrimental effects of radiation. However, emerging experimental evidence suggests that this theoretical framework is insufficient for describing extranuclear radiation effects, particularly the response of the mitochondria, an important site of extranuclear, coding DNA. Here, we discuss experimental observations of the effects of ionizing radiation on the mitochondria at (1) the DNA and (2) functional levels. The roles of mitochondria in (3) oxidative stress and (4) late radiation effects are discussed. In this review, we summarize the current understanding of targets for ionizing radiation outside the cell nucleus. Available experimental data suggest that an increase in the tumoricidal efficacy of radiation therapy might be achievable by targeting mitochondria. Likewise, more specific protection of mitochondria and its coding DNA should reduce damage to healthy cells exposed to ionizing radiation.     

Physiological changes leading to anhydrobiosis improve radiation tolerance in Polypedilum vanderplanki larvae

High tolerance against various extreme environments exhibited by some anhydrobionts might be due to being almost completely desiccated, a state where little or no chemical reactions occur. We have shown that anhydrobiotic larvae of Polypedilum vanderplanki have higher tolerance against both high- and low-linear energy transfer (LET) radiation than hydrated larvae. It is of great interest to know how the desiccating larvae gain radiation tolerance. We therefore examined effects of high-LET radiation on four kinds of larvae: (1) normal hydrated (intact) larva, (2) intermediates between the anhydrobiotic and normal hydrated state, (3) almost completely dehydrated (anhydrobiotic) larvae, and (4) immediately rehydrated larvae that are assumed to have a similar molecular profile to anhydrobiotic larvae. The intermediates and immediately rehydrated larvae survived longer after high-LET radiation than intact larvae, indicating that radiation tolerance could be enhanced even in hydrated larvae. Physiological changes toward anhydrobiosis, e.g. accumulation of protectants or increasing damage repair capacity, correlate with improved radiation tolerance in hydrated larvae. In addition, almost complete desiccation further enhanced radiation tolerance, possibly in a different way from the hydrated larvae.     

Structure of the Mn<Subscript>4</Subscript>–Ca cluster as derived from X-ray diffraction

The catalytic centre for light-induced water oxidation in photosystem II (PSII) is a multinuclear metal cluster containing four manganese and one calcium cations. Knowing the structure of this biological catalyst is of utmost importance for unravelling the mechanism of water oxidation in photosynthesis. In this review we describe the current state of the X-ray structure determination at 3.0 A resolution of the water oxidation complex (WOC) of PSII. The arrangement of metal cations in the cluster, their coordination and protein surroundings are discussed with regard to spectroscopic and mutagenesis studies. Limitations of the presently available structural data are pointed out and possible perspectives for the future are outlined, including the combination of X-ray diffraction and X-ray spectroscopy on single crystals.