The role of metformin on the radiosensitising effect of cisplatin is not clear. Here we investigated the radiosensitising effect of metformin alone and combined with cisplatin in HeLa cells, as well ...as the implications of the adenosine monophosphate-activated protein kinase (AMPK) pathway on the radiosensitising effect.
HeLa cells were treated with ionising radiation, metformin, cisplatin, A769662 (AMPK activator) and dorsomorphin (AMPK inhibitor) or in combination. A cell proliferation assay, Western blot and flow cytometry were carried out.
Metformin potentiated cisplatin cytotoxicity when administered 4 h before ionising radiation. Although the radiosensitising effects of metformin and cisplatin alone were observed, which is more apparent at high ionising radiation doses, the metformin–cisplatin combination did not increase the radiosensitivity of cisplatin at any ionising radiation dose. Dorsomorphin alone significantly decreased cell proliferation and potentiated the radiosensitising effects of cisplatin with ionising radiation. Administration of A769662 24 h prior to cisplatin treatment resulted in an increased AMPK level that yielded resistance to cisplatin, but this effect was not observed in HeLa cells concomitantly treated with A769662 and cisplatin.
Modulation of AMPK may have a role in cervical cancer treatment. Increased AMPK levels result in higher sensitivity to ionising radiation but causes resistance to cisplatin. Dorsomorphin is proven to be a potent radiosensitising agent. The use of metformin alone may be an option as a radiosensitiser during high-dose ionising radiation (e.g. intracavitary brachytherapy).
•Increased AMPK levels result in higher sensitivity to ionising radiation, while causing resistance to cisplatin.•Dorsomorphin proves to be a potent radiosensitising agent.•Metformin alone may be an option as a radiosensitiser during high-dose ionising radiation (e.g. intracavitary brachytherapy).
Somatic mutations or deletions of TP53 and PTEN in ductal carcinoma in situ lesions have been implicated in progression to invasive ductal carcinomas. A recent molecular and mutational analysis of ...breast cancers revealed that inactivation of tumor suppressors, p53 and PTEN, are strongly associated with triple negative breast cancer. In addition, these tumor suppressors have important roles in regulating self-renewal in normal and malignant stem cells. To investigate their role in breast carcinogenesis, we knocked down these genes in human mammary cells and in non-transformed MCF10A cells. p53 and PTEN knockdown synergized to activate pro-inflammatory interleukin-6 (IL6)/Stat3/nuclear factor κB signaling. This resulted in generation of highly metastatic epithelial-to-mesenchymal transition-like cancer stem cells resulting in tumors whose gene expression profile mimicked that found in basal/claudin-low molecular subtype within the triple negative breast tumors. Constitutive activation of this loop in transformed cells was dependent on proteolytic degradation of suppressor of cytokine signaling 3 (SOCS3) resulting in low levels of this protein in basal/claudin-low cell lines and primary tumors. In non-transformed cells, transient activation of the IL6 inflammatory loop induced SOCS3 expression leading to pathway inactivation. In transformed cells, enforced expression of SOCS3 or interfering with IL6 pathway via IL6R blockade inhibited tumor growth and metastasis in mouse xenograft models. Furthermore, circulating tumor cells were significantly reduced in tumor-bearing animals when treated with anti-IL6R antibodies. These studies uncover important connections between inflammation and carcinogenesis and suggest that blocking pro-inflammatory cytokines may be utilized as an attractive strategy to target triple negative breast tumors, which currently lacks molecularly targeted therapies.
The purpose of this study was to determine the effects of arbuscular mycorrhizal (AM) inoculation on the quality of einkorn wheat straw (EWS) and in vitro gas production (GP). It was found that AM ...inoculation of EW seed before sowing caused significant increases in crude protein (CP), ether extract (EE), neutral detergent fibre (NDF), zinc (Zn), copper (Cu), and iron (Fe) levels of straw, and a (P 0.05). Thus, inoculation of einkorn wheat with AM altered the nutritional value of the straw produced creating a roughage with decreased value for feeding ruminant livestock.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The optimal management of locally recurrent prostate cancer after curative radiotherapy is still unknown. In this study, we evaluated the preliminary results of reirradiation using stereotactic body ...radiotherapy for locally recurrent prostate cancer after initial definitive local radiotherapy.
Between April 2016 and February 2019, 11 patients with recurrent disease at the previously irradiated prostate were treated. Local recurrence was detected by radiological with or without functional imaging modalities including prostate multiparametric/pelvic MRI or positron-emission tomography–computerised tomography with (68Ga)-labelled prostate-specific membrane antigen performed after rising prostate specific antigen serum level during follow-up. All patients received stereotactic body radiotherapy to the recurrent nodule to a total dose of 30Gy in five fractions. Hyaluronic acid spacer was injected between prostate and rectum in seven patients to decrease the rectal dose. Acute toxicity was evaluated by using Common Terminology Criteria for Adverse Events version 4.0, and late toxicity was evaluated by using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema.
At the diagnosis, the median age was 64 years, and the mean prostate specific antigen serum concentration was 17.7ng/mL. The median interval time between local recurrence and initial definitive radiotherapy was 63 months. Mean prostate specific antigen concentration nadir value during follow-up was 0.43ng/mL. With a median follow up of 19 months, three patients developed either local or distant relapse. One patient had grade 3 acute rectal toxicity, and one patient had grade 2 late urinary toxicity. We did not observe any acute or late toxicity due to hyaluronic acid spacer injection.
Reirradiation after local recurrence following initial definitive radiotherapy together with hyaluronic acid spacer use seems to be effective and safe.
La prise en charge optimale du cancer de la prostate récidivant localement après radiothérapie à visée curative est encore inconnue. Dans cette étude, nous avons évalué les résultats préliminaires de la réirradiation en utilisant la radiothérapie en conditions stéréotaxiques corporelles pour une récidive locale après radiothérapie à visée curative.
Entre avril 2016 et février 2019, 11 patients atteints d’une maladie récidivante de la prostate précédemment irradiée ont été pris en charge. La décision de récidive a été prise par les modalités d’imagerie radiologique métabolique ou non, y compris l’IRM multiparamétrique/pelvienne de la prostate ou la tomographie par émission de positrons–scanographie à l’antigène membranaire spécifique de la prostate marquée au gallium-68 effectuées après une augmentation de la concentration sérique d’antigène spécifique de la prostate pendant le suivi. Tous les patients ont reçu une radiothérapie en conditions stéréotaxiques du nodule récidivant de 30Gy en cinq fractions. Un espaceur d’acide hyaluronique a été injecté entre la prostate et le rectum chez sept patients pour abaisser la dose dans le rectum. La toxicité aiguë a été évaluée en utilisant la version 4.0 des Common Terminology Criteria for Adverse Events (CTCAE), et la toxicité tardive en utilisant le schéma de notation de la morbidité tardive du Radiation Therapy Oncology Group (RTOG) et de l’European Organisation for Research and Treatment of Cancer (EORTC).
L’âge médian des patients était de 64 ans et la concentration moyenne d’antigène spécifique de la prostate de 17,7ng/mL. Une récidive locale a été retrouvée avec une médiane de 63 mois après la radiothérapie initiale. La valeur moyenne du nadir d’antigène spécifique de la prostate pendant le suivi était de 0,43ng/mL. Avec une durée médiane de suivi de 19 mois, trois patients ont été atteints d’une rechute locale ou distante et deux d’entre eux d’une maladie systémique sur l’imagerie 6 mois après la radiothérapie en conditions stéréotaxiques. Au cours du suivi, un patient a souffert d’une toxicité rectale aiguë de grade 3 et un, d’une toxicité urinaire tardive de grade 2. Les patients chez qui l’espaceur d’acide hyaluronique a été utilisé n’ont signalé aucune toxicité aiguë ni tardive.
La réirradiation après une récidive locale après une radiothérapie initiale semble efficace et sûre. L’utilisation d’un espaceur d’acide hyaluronique n’était associée à aucune toxicité liée au traitement.
The purpose of this study was to determine the effect of arbuscular mycorrhizae (AM) inoculation, which was administered to increase the quality of einkorn wheat in its fatty acid composition, ...quality and mineral concentration. Wheat grown from AM inoculated seed (AM+) had increased the dry matter (DM), iron (Fe), monounsaturated fatty acids (MUFA), especially oleic acid, and alpha-linolenic acid, and cis-5,-8,-11,14, and cis-17 eicosapentaenoic acid from polyunsaturated fatty acids (PUFA) (P <0.05), but decreased crude ash (CA), potassium (K), and total saturated fatty acids (UFA), especially myristic acid, palmitic acid, stearic acid and monounsaturated fatty acids, especially cis-palmitoleic acid, cis-10-heptadecenoic acid, cis11 eicosenoic acid, erucic acid, and linoleic acid (P <0.05) compared with einkorn wheat grown from noninoculated seed (AM-). Crude protein (CP) content ranged from 10.56% to 10.68%, and ether extract (EE) content varied between 2.03% and 2.41%, neither of which was significantly different between treatments. Significant increases were observed in UFA, and in the ratios of UFA to SFA and PUFA to SFA in AM+ compared with AM-.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemic clones of
Acinetobacter baumannii
, described as European clones I, II, and III, are associated with hospital epidemics throughout the world. We aimed to determine the molecular ...characteristics and genetic diversity between European clones I, II, and III from Turkey and Azerbaijan. In this study, a total of 112 bloodstream isolates of carbapenem-resistant
Acinetobacter
spp. were collected from 11 hospitals across Turkey and Azerbaijan. The identification of
Acinetobacter
spp. using conventional and sensitivity tests was performed by standard criteria. Multiplex polymerase chain reaction (PCR) was used to detect OXA carbapenemase-encoding genes (
bla
OXA-23-like
,
bla
OXA-24-like
,
bla
OXA-51-like
, and
bla
OXA-58-like
). Pulsed-field gel electrophoresis (PFGE) typing was used to investigate genetic diversity. The
bla
OXA-51-like
gene was present in all 112 isolates, 75 (67 %) carried
bla
OXA-23-like
, 7 (6.2 %) carried
bla
OXA-58-like
genes, and 5 (4.5 %) carried
bla
OXA-24-like
genes. With a 90 % similarity cut-off value, 15 clones and eight unique isolates were identified. The largest clone was cluster D, with six subtypes. Isolates from clusters D and I were widely spread in seven different geographical regions throughout Turkey. However, F cluster was found in the northern and eastern regions of Turkey. EU clone I was grouped within J cluster with three isolates found in Antalya, Istanbul, and Erzurum. EU clone II was grouped in the U cluster with 15 isolates and found in Kayseri and Diyarbakır. The
bla
OXA-24-like
gene in carbapenemases was identified rarely in Turkey and has been reported for the first time from Azerbaijan. Furthermore, this is the first multicenter study in Turkey and Azerbaijan to identify several major clusters belonging to European clones I and II of
A. baumannii
.
Background: Controlling Nutritional Assessment (CONUT) score has been shown to have a higher predictive value compared to other nutritional scores in acute coronary syndrome. Aim: To determine the ...relationship between CONUT score and long-term mortality in patients with chronic coronary syndrome (CCS). Methods: Between 2017 and 2020, 585 consecutive patients newly diagnosed and proven to have CCS by coronary angiography were included in the study. CONUT score and demographic and laboratory data of all patients were evaluated. The relationship between results and mortality was evaluated. Results: The mean age of the patients was 64 years and 75% were male. Mortality was observed in 56 (9.6%) patients after a median follow-up period of 3.5 years. The median CONUT score was significantly higher in patients with mortality ( P < 0.001). In multivariate regression analysis, the CONUT score was associated with mortality (Hazard ratio (HR): 1.63 (95% confidence interval (CI): 1.34–1.98 P < 0.001)). The area under curve (AUC) for long-term mortality estimation for the CONUT score was 0.75 (95% CI 0.67–0.82 P < 0.001). When the CONUT score value was accepted as 0.5, the sensitivity was 78% and the specificity was 60 %. Conclusion: CONUT score was found to be predictive of mortality in long-term follow-up of patients with CCS.
Summary
A new model to predict the non-ideal detonation behaviour of commercial explosives in rock blasting is presented. The model combines the slightly divergent flow theory, polytropic equation of ...state, simple pressure-dependent rate law and statistical expressions to model the effect of confinement on detonation. The model has been designated as DeNE, an acronym for the Detonics of Non-ideal Explosives. It is aimed at predicting the detonation state and subsequent rarefaction (Taylor) wave to provide the pressure history for different explosive, rock type and blasthole diameter combinations. It enables the prediction and comparison of the performance of commercial explosives in different blasting environments. The unconfined detonation velocity data has been obtained from the testing of six commercial explosives to calibrate DeNE. A detailed sensitivity analysis has been conducted to evaluate the model. The model has been validated using the results of hydrocodes as well as measured and published in-hole detonation velocity data.
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