The outcomes of three-dimensional conformal radiotherapy for early-stage non-small-cell lung cancer patients eligible and ineligible for stereotactic body radiotherapy

Wstęp: Radioterapia stereotaktyczna (SBRT) daje obiecujące, porównywalne z leczeniem chirurgicznym, wyniki u chorych na niedrobnokomórkowego raka płuca (NDRP) we wczesnych stopniach zaawansowania. Jednak nie wszyscy chorzy z tej grupy kwalifikują się do tej metody leczenia. Dokonano retrospektywnej oceny wyników radioterapii konformalnej (3D-CRT) u chorych na NDRP w I i II stopniu zaawansowania, ze szczególnym uwzględnieniem wyników chorych, którzy byliby kandydatami do SBRT, lecz u których z braku dostępu do tej techniki zastosowano 3D-CRT. Materiał i metody: Oceniono kolejnych 132 chorych na NDRP (I&#8211;II stopień) napromienianych radykalnie techniką 3D-CRT w latach 1998&#8211;2009. Stosowano różne schematy napromieniania. W związku z tym dokonano przeliczenia dawek na dawki biologicznie równoważne (BED). W grupie tej 68 chorych spełniało kryteria napromieniania techniką SBRT (obwodowy guz T1&#8211;3N0, średnica &#163; 5 cm). Przeżycie całkowite i wolne od progresji miejscowej oszacowano metodą Kaplana-Meiera dla całej grupy oraz grupy spełniającej kryteria i niespełniającej kryteriów SBRT. Dokonano oceny czynników rokowniczych w analizie jedno- i wielowariantowej. Wyniki: Mediana BED w całej grupie wyniosła 74 Gy (58&#8211;82 Gy). Chorzy spełniający kryteria SBRT mieli mniejszą objętość guza niż pozostali (p < 0,00001). Trzyletnie przeżycie całkowite i przeżycie wolne od progresji miejscowej wyniosły odpowiednio 37% i 50%. Porównując grupy potencjalnie kwalifikujące się i niekwalifikujące się do SBRT, uzyskano znamienną statystycznie różnicę jedynie w 3-letnim przeżyciu bez progresji miejscowej (odpowiednio 58% i 35%, p = 0,04). W analizie wielowariantowej tylko objętość guza, stan ogólny i stopień zaawansowania miały statystycznie znamienny związek z miejscową wyleczalnością. Wnioski: Wykazano poprawę wyleczalności miejscowej po zastosowaniu techniki 3D-CRT w przypadku guzów spełniających kryteria kwalifikacji do SBRT w stosunku do pozostałych. Jednak również w tych przypadkach miejscowa wyleczalność była gorsza od podawanych w piśmiennictwie wyników SBRT. Pneumonol. Alergol. Pol. 2011; 79, 5: 326&#8211;336Introduction: Stereotactic body radiotherapy (SBRT) in early-stage non-small-cell lung cancer (NSCLC) results in promising outcomes, comparable with the outcomes of surgery. However, not all such patients are good candidates for this treatment. We conducted a retrospective evaluation of the outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with stage I/II NSCLC with a special focus on the outcomes of patients who were eligible for SBRT but received 3D-CRT due to the unavailability of the former. Material and methods: We evaluated 132 consecutive patients with stage I/II NSCLC who had received radical 3D-CRT between 1998 and 2009. As various radiotherapy schedules had been used, biologically equivalent doses (BEDs) were calculated for all the patients. A total of 68 patients were eligible for SBRT (peripheral T1-3 N0 tumours < 5 cm in diameter). Overall survival (OS) and local progression free survival (LPFS) were estimated using Kaplan-Meier methodology for the entire study population and for the groups eligible and ineligible for SBRT. Univariate and multivariate analyses were performed for the prognostic factors. Results: Median BED in the study population was 74 Gy (58&#8211;82 Gy). Patients eligible for SBRT had a significantly lower gross tumour volume (GTV) than the other patients (p < 0.00001). Three-year OS and LPFS were 37% and 50%, respectively. When we compared patients eligible for SBRT and those ineligible for SBRT the only significant difference was for three-year LPFS (58% v. 35%, p = 0.04). Multivariate analysis showed that only GTV, performance status and tumour stage were significantly correlated with local curability. Conclusions: We showed an improved local control following 3D-CRT in patients eligible for SBRT compared to the other patients. However, also in these cases, local control was inferior compared to the outcomes of SBRT reported in the literature. Pneumonol. Alergol. Pol. 2011; 79, 5: 326&#8211;33

Isolated nodal failure after chemo-radiotherapy in limited disease small cell lung cancer (LD-SCLC)

BackgroundThe irradiation volume for treatment of limited disease small cell lung cancer (LD-SCLC), are still controversial. One of the aspects of radiation volume is the use of elective nodal irradiation (ENI), which has never been subjected to randomized study in SCLC patients.AimTo review retrospectively patterns of failure in relation to the radiation field after chemoradiotherapy (CHT-RT) in patients with limited disease small cell lung cancer (LD-SCLC).Material and MethodsBetween 1997 and 2006, 117 consecutive patients with LD-SCLC received chemotherapy with sequential radiotherapy (70%) and concurrent or alternating CHT-RT (30%). All but one case had predefined elective nodal irradiation (ENI) without inclusion of supraclavicular regions. Prophylactic cranial irradiation (PCI) was administered to 39% of patients.ResultsThe median follow-up for the 20 living patients was 33 months. The overall survival at 2 years was 36% (median survival: 18 months). In-field locoregional progression was observed in 42 patients (36%). Distant metastases occurred in 71 patients (61%). Five patients (4%) developed isolated nodal failure (INF) without local progression in the supraclavicular region. Patients with INF had N3 disease more often than those without INF (60% vs 21%, p = 0.04). There was 5% RTOG grade 3 or higher early radiation toxicity.ConclusionsINF failures are rare; however, the need for extension of ENI to supraclavicular areas may be reconsidered in N3 patients

Pegylation – in search of balance and enhanced bioavailability

In the process of finding better therapeutics, thousands of new molecules are synthesised every day. Many of these can be poorly soluble in water, leading to a potentially promising drug being rejected during testing due to its poor solubility. Polyethylene glycol (PEG) has become known as an excellent modification to remedy this and was initially used to increase circulation time and reduce the immunogenicity of therapeutic proteins. Thus significantly increasing their safety and range of use. Another group of compounds in which significant benefits of pegylation have been seen are photosensitisers. Used in photodynamic therapy, they are often characterised by very high hydrophobicity. Pegylation of their structure significantly increases their affinity for cancer cells and facilitates their penetration through cell membranes. Classical small-molecule drugs can benefit from temporary combinations hydrolysed in the body or very short PEG chains. This approach allows a significant increase in the bioavailability of the drug while avoiding the disadvantages of small molecule pegylation. However, the most common motive for pegylation recently is the creation of drug carriers. Liposomes and nanoparticles make it possible to exploit the advantages of PEG to stabilise their structure and increase circulation time while not modifying the structure of the active compound. Unfortunately, PEGs also have their drawbacks. The first is their high molecular weight range, especially for longer chains, which poses difficulties in purification. Another is the emergence of antibodies directed against PEG. Nevertheless, pegylation is still an up-and-coming method for modifying pharmaceutically active molecules

Characterization of AIIIBV\mathrm{A^{III}B^V} superlattices by means of synchrotron diffraction topography and high-resolution X-ray diffraction

New possibilities are presented for the characterization of A$^{III}$B$^V$ mixed superlattice compounds by the complementary use of synchrotron diffraction topography and rocking curves. In particular, using a synchrotron white beam and the section diffraction pattern of a 5 µm slit taken at a 10 cm film-to-crystal distance, it was possible to reproduce a set of stripes corresponding to interference fringes. These are analogous to the interference maxima revealed in high-resolution rocking curves, but are created by the changes in orientation of the planes inclined to the surface which are induced by unrelaxed strain. The section diffraction topographic method enabled examination of the sample homogeneity along the narrow intersecting beam. This was important in the case of the present sample containing a twin lamella in the InP substrate wafer. Both the section and projection Bragg case topographic methods enabled the crystallographic identification of the twin lamella. Another characteristic feature indicated in the section topography was the bending of the stripes corresponding to the superlattice peaks close to the boundaries of the twin lamella. The most probable interpretation of this phenomenon is an increase in the thickness of the deposited layers close to the lamella, together with possible changes in the chemical composition, leading to a decrease in the mean lattice parameter in the superlattice

Characterization of A

New possibilities are presented for the characterization of A$^{III}$B$^V$ mixed superlattice compounds by the complementary use of synchrotron diffraction topography and rocking curves. In particular, using a synchrotron white beam and the section diffraction pattern of a 5 µm slit taken at a 10 cm film-to-crystal distance, it was possible to reproduce a set of stripes corresponding to interference fringes. These are analogous to the interference maxima revealed in high-resolution rocking curves, but are created by the changes in orientation of the planes inclined to the surface which are induced by unrelaxed strain. The section diffraction topographic method enabled examination of the sample homogeneity along the narrow intersecting beam. This was important in the case of the present sample containing a twin lamella in the InP substrate wafer. Both the section and projection Bragg case topographic methods enabled the crystallographic identification of the twin lamella. Another characteristic feature indicated in the section topography was the bending of the stripes corresponding to the superlattice peaks close to the boundaries of the twin lamella. The most probable interpretation of this phenomenon is an increase in the thickness of the deposited layers close to the lamella, together with possible changes in the chemical composition, leading to a decrease in the mean lattice parameter in the superlattice

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

Resveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxidant and phytoestrogen. The phytoestrogenic activity of resveratrol was assayed in different in vitro and in vivo models. Although these works brought some, on the first look, conflicting results, it is commonly accepted that resveratrol interacts with estrogen receptors and functions as a mixed agonist/antagonist. It is widely accepted that the hydroxyl groups are crucial for resveratrol’s cytotoxic and antioxidative activity and are responsible for binding estrogen receptors. In this work, we assayed 11 resveratrol analogues, seven barring methoxy groups and six hydroxylated analogues in different combinations at positions 3, 4, 5 and 3′,4′,5′. For this purpose, recombined estrogen receptors and estrogen-dependent MCF-7 and Ishikawa cells were used. Our study was supported by in silico docking studies. We have shown that, resveratrol and 3,4,4′5′-tetrahydroxystilbene, 3,3′,4,5,5′-pentahydroxystilbene and 3,3′,4,4′,5,5′-hexahydroxystilbene may act as selective estrogen receptor modulators

High Potency of a Novel Resveratrol Derivative, 3,3′,4,4′-Tetrahydroxy-trans-stilbene, against Ovarian Cancer Is Associated with an Oxidative Stress-Mediated Imbalance between DNA Damage Accumulation and Repair

We explored the effect of a new resveratrol (RVT) derivative, 3,3′,4,4′-tetrahydroxy-trans-stilbene (3,3′,4,4′-THS), on viability, apoptosis, proliferation, and senescence of three representative lines of ovarian cancer cells, that is, A2780, OVCAR-3, and SKOV-3, in vitro. In addition, the mechanistic aspects of 3,3′,4,4′-THS activity, including cell redox homeostasis (the production of reactive oxygen species, activity of enzymatic antioxidants, and magnitude of DNA damage accumulation and repair), and the activity of caspases (3, 8, and 9) and p38 MAPK were examined. The study showed that 3,3′,4,4′-THS affects cancer cell viability much more efficiently than its parent drug. This effect coincided with increased generation of reactive oxygen species, downregulated activity of superoxide dismutase and catalase, and excessive accumulation of 8-hydroxy-2′-deoxyguanosine and its insufficient repair due to decreased expression of DNA glycosylase I. Cytotoxicity elicited by 3,3′,4,4′-THS was related to increased incidence of apoptosis, which was mediated by caspases 3 and 9. Moreover, 3,3′,4,4′-THS inhibited cancer cell proliferation and accelerated senescence, which was accompanied by the activation of p38 MAPK. Collectively, our findings indicate that 3,3′,4,4′-THS may constitute a valuable tool in the fight against ovarian malignancy and that the anticancer capabilities of this stilbene proceed in an oxidative stress-dependent mechanism