Purpose: The unique mechanism of tumor destruction by photodynamic therapy (PDT), resulting from apoptotic and necrotic killing of tumor cells accompanied by local inflammatory reaction and induction of heat shock proteins (HSPs), prompted us to investigate the antitumor effectiveness of the combination of PDT with administration of immature dendritic cells (DCs). Experimental Design: Confocal microscopy and Western blotting were used to investigate the influence of PDT on the induction of apoptosis and expression of HSP expression in C-26 cells. Confocal microscopy and flow cytometry studies were used to examine phagocytosis of PDT-treated C-26 cells by DCs. Secretion of interleukin (IL)-12 was measured with ELISA. Cytotoxic activity of lymph node cells was evaluated in a standard 51Cr-release assay. The antitumor effectiveness of PDT in combination with administration of DCs was investigated in in vivo model. Results: PDT treatment resulted in the induction of apoptotic and necrotic cell death and expression of HSP27, HSP60, HSP72/73, HSP90, HO-1, and GRP78 in C-26 cells. Immature DCs cocultured with PDT-treated C-26 cells efficiently engulfed killed tumor cells, acquired functional features of maturation, and produced substantial amounts of IL-12. Inoculation of immature DCs into the PDT-treated tumors resulted in effective homing to regional and peripheral lymph nodes and stimulation of cytotoxic activity of T and natural killer cells. The combination treatment with PDT and administration of DCs produced effective antitumor response. Conclusions: The feasibility and antitumor effectiveness demonstrated in these studies suggest that treatment protocols involving the administration of immature DCs in combination with PDT may have clinical potential.
The diaphragm is the primary muscle involved in active inspiration and serves also as an important anatomical landmark that separates the thoracic and abdominal cavity. However, the diaphragm muscle like other structures and organs in the human body has more than one function, and displays many anatomic links throughout the body, thereby forming a ‘network of breathing’. Besides respiratory function, it is important for postural control as it stabilises the lumbar spine during loading tasks. It also plays a vital role in the vascular and lymphatic systems, as well as, is greatly involved in gastroesophageal functions such as swallowing, vomiting, and contributing to the gastroesophageal reflux barrier. In this paper we set out in detail the anatomy and embryology of the diaphragm and attempt to show it serves as both: an important exchange point of information, originating in different areas of the body, and a source of information in itself. The study also discusses all of its functions related to breathing.
1 February 2018 in Critical Reviews in Oncology/Hematology
The diaphragm is well known for its role as the principal muscle of respiration. However, according to previous studies, its role is multifactorial, from breathing through pain perception, regulation of emotional sphere, collaborating in gastroesophageal functions, facilitating the venous and lymphatic return, to an essential role in the maintenance of lumbar spine stability. The purpose of the study was to examine whether diaphragm function parameters (thickness and range of motion) are associated with static balance maintenance. A total of 142 participants were examined and divided into three groups: G1—patients qualified for lung resection due to cancer; G2 –patients after lobe resection; G3 –healthy subjects. Diaphragm thickness and excursion was measured using ultrasonography. Stabilometric parameters of balance were assessed by Zebris FDM-S platform. Greater diaphragm thickening during active breathing and diaphragm thickness fraction were associated with better static balance parameters. Limitation of diaphragm motion during quiet breathing and deep breathing was linked to balance disorders. There was no correlation between diaphragm muscle excursion during sniff maneuvers and balance parameters. Deterioration of diaphragm function observed after thoracic surgery was closely related with deterioration of balance maintenance. Impairment of diaphragm function manifested by decrease of muscle thickness and movement restriction is strongly associated with balance disorders in a clinical sample and among healthy subjects.
In the global context, the epidemic of breast cancer (BC) is evident for the early 21st century. Evidence shows that national mammography screening programs have sufficiently reduced BC related mortality. Therefore, the great utility of the mammography-based screening is not an issue. However, both false positive and false negative BC diagnosis, excessive biopsies, and irradiation linked to mammography application, as well as sub-optimal mammography-based screening, such as in the case of high-dense breast tissue in young females, altogether increase awareness among the experts regarding the limitations of mammography-based screening. Severe concerns regarding the mammography as the “golden standard” approach demanding complementary tools to cover the evident deficits led the authors to present innovative strategies, which would sufficiently improve the quality of the BC management and services to the patient. Contextually, this article provides insights into mammography deficits and current clinical data demonstrating the great potential of non-invasive diagnostic tools utilizing circulating miRNA profiles as an adjunct to conventional mammography for the population screening and personalization of BC management.
19 May 2017 in Journal of Cellular and Molecular Medicine
It is supposed that plant functional foods, rich in phytochemicals, may potentially have preventive effects in carcinogenesis. In this study, the anticancer effects of cloves in the in vivo and in vitro mammary carcinoma model were assessed. Dried flower buds of cloves (CLOs) were used at two concentrations of 0.1% and 1% through diet during 13 weeks after the application of chemocarcinogen. After autopsy, histopathological and immunohistochemical analyses of rat mammary carcinomas were performed. Moreover, in vitro evaluation using MCF‐7 cells was carried out. Dietary administered CLO caused the dose‐dependent decrease in tumour frequency by 47.5% and 58.5% when compared to control. Analysis of carcinoma cells in animals showed bcl‐2, Ki67, VEGFA, CD24 and CD44 expression decrease and Bax, caspase‐3 and ALDH1 expression increase after high‐dose CLO administration. MDA levels were substantially decreased in rat carcinomas in both CLO groups. The evaluation of histone modifications revealed increase in lysine trimethylations and acetylations (H4K20me3, H4K16ac) in carcinomas after CLO administration. TIMP3 promoter methylation levels of CpG3, CpG4, CpG5 islands were altered in treated cancer cells. An increase in total RASSF1A promoter methylation (three CpG sites) in CLO 1 group was found. In vitro studies showed antiproliferative and pro‐apoptotic effects of CLO extract in MCF‐7 cells (analyses of cytotoxicity, Brdu, cell cycle, annexin V/PI, caspase‐7, Bcl‐2 and mitochondrial membrane potential). This study showed a significant anticancer effect of clove buds in the mammary carcinoma model in vivo and in vitro.