1Instituto de Quimica de São Carlos, Universidade de São Paulo, Brazil
2Departamento de Química, Universidade Federal de São Carlos, Brazil
Photodynamic therapy (PDT) is based on the induction of diseased tissue damage by the combination of three components: a photosensitizer (PS), light of adequated wavelength to the PS, and molecular oxygen leading the cells to produce reactive oxygen species (ROS) and in consequence, apoptotic or necrotic death of the tumor. In this study two new chlorins with L-type shape structure were synthesized from protoporphyrin IX dimethyl ester and 1-(3-phenylpropyl)-1H-pyrrole-2,5-dione by the Diels-Alder reaction aiming to avoid self-aggregation of the chlorins in physiological medium as well as to study the photodynamic action on HEp-2 tumor cells and Vero non-tumor cells. The chlorins CHL-Ph-A e CHL-Ph-B were characterized by 1H-NMR, 13C-NMR, UV-Vis and high resolution mass spectroscopy (HRMS). Their photochemical properties were determined such as quantum yield of singlet oxygen with a value around f0 = 0.69 and fluorescence quantum yield (ff = 0.0148) along with their photodegradation. The partition coefficient (Log P) of the CHL-Ph-A is 1.44 ± 0.06 and 1.42 ± 0.03 for the CHL-Ph-B showing an important amphiphilic character. The synthesized chlorins have a strong emission in 670 nm in DMSO (ԑ = ~2.20 x 104 M-1 cm-1), very low photobleaching, no aggregation, and a good phototoxicity leading to cell death by an apoptotic process in tumor cells as observed by fluorescence microscopy. The IC50 of the chlorins in tumor cells are as low as 65 nM for HEp-2 cells and they exhibited no cytotoxicity in nontumour cells, demonstring selectivity. The results suggest that these chlorins derivatives are potential candidates to photosensitizers for PDT of cancer.
1. Linares, I.A.P., et al., Dyes and pigments, 145 (2017) 518.
2. Uchoa, A.F., et al., J Org Chem, 76 (2011) 8824.
3. Moritz, M.N.O, et al., Photodiagnosis and Photodynamic Therapy, 17 (2017) 39.
4. dos Santos, F.A.B., et al., Dyes and pigments, 99 (2013) 402.
Acknowledgements: The authors wish to thank the CNPq, FAPESP (CEPOF) and CAPES for financial support and fellowships.
Applied Biology, Faculty of Pharmacy and Science of Nutrition and of Health at University of Calabria, Italy
Introduction: Progesterone Receptor (PR) positivity is associated with a good prognosis and better response to breast cancer treatment. Conversely, cyclin D1 (CD1) is retained a marker of poor outcome since it has been associated with breast cancer metastasis in clinical studies.
Material and Method: 17-Hydroxyprogesterone (OHPg) was from Sigma-Aldrich. Antibodies and Protein A/GPLUS-Agarose were from Santa Cruz Biotechnology. T47-D, MCF-7 and MDA-MB-231 human breast cancer cells from the American Type Culture Collection; Total real-time RT-PCR assay; Western blotting and immunoprecipitation; Transfections and luciferase assays; Lipid-Mediated Transfection of siRNA Duplexes; Chromatin immunoprecipitation (ChIP) assays and realtime ChIP; Wound-healing assays; Transmigration assays; Cell invasion assay; Phalloidin staining
Results and Discussion: Herein we provide evidences that OHPg through PR-B isoform, reduces motility and invasion of T47-D and MCF-7 breast cancer cells, by targeting the cytoplasmic CD1. Specifically, OHPg reduces CD1 expression through a transcriptional mechanism due to the occupancy of CD1 promoter at a canonical half progesterone responsive element by PR-B. This allows the recruitment of HDAC1 influencing a less permissive chromatin conformation for gene transcription and release of RNA Pol II. CD1 has an active role in the control of cell migration and metastasis through the interaction with key components of focal adhesion such as Paxillin (Pxn). In untreated T47-D and MCF-7 cells a specific co-immunoprecipitation of endogenous cytoplasmic CD1 with Pxn was observed. In untreated T47-D and MCF-7 cells a specific co-immunoprecipitation of endogenous cytoplasmic CD1 with Pxn was detected. Interestingly, OHPg exposure reduced the interaction between these proteins although total Pxn expression was substantially unaffected. Moreover a concomitant reduction of p-Pxn levels was observed and these effects were required for OHPg/PR-B dependent delay in cell invasion, as evidenced by assays carried out with the phoshomimetic mutants of Pxn.
Conclusions: Collectively these findings support the importance of PR-B expression in breast cancer cells behavior, suggesting potentiating of PR-B signaling as a prospective useful strategy to restrict breast tumour cells invasion and metastasis.
Francesca De Amicis is an Assistant Professor of Applied Biology, Faculty of Pharmacy and Science of Nutrition and of Health at University of Calabria, Italy. In 1992 he did his Ph.D in Experimental Oncology, Italy. From 2005-2006 he was an Postdoctoral Associate at Breast Center, Baylor College of Medicine, Houston-Texas, USA. His Research Interests include Role of Steroid receptors in tumorogenesis of hormone-dependent tissues.
P.A. Hertsen Moscow Oncology Research Center, Russia
Stomach cancer (RJ) remains an urgent health problem.
Purpose of the study: Analysis of the state of oncological care for breast cancer and ways of improvment in the Republic of North Ossetia-Alania (RNO-Alania).
Materials and Methods: Forms No. 7, 35, 5 (Table C51), Table 2 PH, the history of diseases of the deceased.
Results: For 20 years on treatment there were 2499 patients with RZ in the Republican Oncology Dispensary. Men - 1404 (56.2%) and women - 1095 (34.8%). The average age of patients was 65.1 (65.4 m, 66.2 w.).
The standardized indicator (world standard) of the incidence, in general, was 12.1 (m. - 17.8 and w-8.5) per 100 000 population. The incidence of men is 2.1 times greater than that of women. The averaged five-year figures for both sexes in 1993-1997. - 14.5; 1998-2002 - 12.2; 2003-2007 - 11.4; 2008-2012 - 10.4. The indicator of the last 5-year period compared with the first decreased by 1.4 times. In men, these indicators: 21.0, 17.5, 17.1 and 15.5 respectively. Decrease in 1,4 times. In women: 10.3, 8.7, 7.8 and 7.1 decrease by 1.5 times. The overall rate of decline is 37.5 (m. - 33.5 and w.41.7). The average annual rate of decline is 1.9 (m - 1.7 and w. - 2.2).
Died 2204 patients from RZ. M. - 1210 (54.9%) and w. - 994 (45.1%). The average age of the deceased is 66.7 (66.2 m, 66.8 w.). The standardized mortality rate in general is 8.1 (m - 10.9 and w. - 5.7) per 100 000 population. Mortality y is 1.9 times greater than that of women. The averaged five-year figures for both sexes in 1993-1997. - 8.7; 1998-2002 - 8.1; 2003-2007 - 7.6; 2008-2012 6.9. The last 5-year indicator in comparison with the first decreased by 1.2 times. In men, these indicators: 13.8, 11.6, 11.4 and 10.3 respectively. Decrease in 1,3 times. In women: 6,8, 5,8, 5,2 and 4,7 decrease in 1,4 times. The rate of decrease is 28.8 (m - 26.4 and w - 31.8). The average annual rate of decline is 1.8 (m - 1.9 and w. - 2.0).
Active detection of RJ on average 1.1%. Morphological verification of the diagnosis 72,4%. Detection of RJ in the I-II stage was 20.8% on average, III - 36.0% and IV stage - 43.2%. The prevalence of RD is 38.6 per 100 000 population on average. Survival of patients 5 years or more on average 42.5%. In the last 5 years compared with the first increased 1.2 times. On average, only 28.2% of patients received special treatment. Surgical 77.4% and combined 22.1%. In the last 5 years, 56.6% of surgical treatment was received, which is 1.5 times lower compared to the first (86.8%), and combined, respectively 43.3 and 13.2, increased 3.3 times. Mortality in the 1st year is on the average 50.6%. The indicator of the last 5-year period compared with the first decreased by 1.2 times.
Conclusion: Incidence of RJ for the observed period decreased. The active detection and detection of RY I-II stages are low, the percentage of neglect is high. Mortality remains high. Survival is 5 years and lower. It is necessary to increase the literacy of the population, carry out endoscopic screening programs of the population at risk for RJ and precancerous gastroduodenal diseases, and their timely treatment.
P.A. Hertsen Moscow Oncology Research Center, Russia
The treatment of malignant neoplasms, despite the enormous successes in oncology, is the main problem of medicine and public health throughout the world
Purpose of the study: Analysis of the state of cancer care and ways to improve it in malignant tumors in the Republic of North Ossetia-Alania (RNO-Alania).
Materials and Methods: Forms No. 7, No. 35, No. 5 (Table No. C51), Table 2 PH.
Results: The main indicators of oncological care for 43596 patients with malignant neoplasms were analyzed. Active detection of patients averaged 8.6%. At averaged 5-year intervals, it corresponded to: 1990-1994. - 6.7%, 1995-1999. - 7.6%, 2005-2009. - 9.4%, 2000-2004 - 10.1%, 2010-2014. - 9.0%, i.e. Has grown in 1,3 times. The diagnosis was verified morphologically in 82.7%. In the last 5-year period (80.1%) compared with the first (75.2%), an improvement of 1.06 times. In the early (I-II) stage, the disease was detected in 52.1%. In the last 5-year period (55.0%) compared with the first (50.6%), an improvement of 1.09 times. In the third stage, on average, 24.0%, in the last and first 5-year period 22.7% and 21.6%. In the IV stage, 23.8%, 22.2% and 23.8%, respectively. There is no improvement in these indicators. The contingent of patients on the register is 1349.6 per 100 000 population. In the last 5-year period (1913.3) compared with the first (949.2) increased by 2 times. However, an average of 51.8% is recorded on the account for 5 years and more, and the indicator of 5-year survival of the last period (52.9%) has not changed compared to the first (52.3%). That is, the growth of this indicator due to the increase in morbidity. In the first year after the diagnosis was established, 26.2% died. In the last 5-year period (24.2%) in comparison with the first (30.6%) decrease in 1.3 times. One-year mortality rate is 41.3%. The indicator of the last 5-year period (43.5%) compared to the first (42.7%) did not change. The number of patients who completed special treatment is 51.4%. The indicator of the last 5-year period (61.7%) compared to the first (44.2%) increased by 1.4 times. Of these, only surgical treatment is 18.6%. The indicator of the last 5-year period (20.4%) compared to the first (16.1%) increased by 1.3 times. Combined or complex treatment received 18.1%. In the last 5-year period (24.9%) compared to the first (12.8%), it increased 1.9 times. Chemoradiation treatment - 0,9%, only medicinal - 2,6%.
Conclusion: The indicators of active detectability and early detection of patients are low. Loss and mortality are high. A low percentage of surgical treatment and a survival rate of 5 years or more. The introduction of screening programs for cancer, increasing the oncological alertness of doctors of the treatment network and medical literacy of the population are mandatory.
P.A. Hertsen Moscow Oncology Research Center, Russia
In Russia, as in many countries of the world, there is an increase in the incidence of colorectal cancer.
Purpose of the study: A retrospective analysis of the state of oncological care for patients with colon cancer and ways to improve it in the Republic.
Materials and Methods: Forms No. 7, No. 35, No. 5 (Table No. C51), Table 2 of RN, the history of the deceased.
Results: For 20 years in the Republican Oncology Dispensary (ROD) for treatment there were 1,821 patients with ROC at the age of 30 to 85 years. The average age is 67 years. In the structure of all tumors, ROC was 4.9%. Localization: the right half - 37.7%, the transverse colon - 6.2%, the left half - 56.1%.
The standardized indicator (world standard) of RBC morbidity for the entire follow-up period averaged 8.6 (m. -9.6, w. -8.0) per 100 000 population. The averaged 10-year indicator (2003-2012) - 9.5 compared to 7.6 (1993-2002) increased by 1.25 times (m. -10.7 and w. 8.4 increased in 1,3 times, w. - 8.8 and 7.2 grew in 1.2 times). This figure for men is 1.2 times more than for women. The increase in morbidity in both sexes is 37.0 (m - 37.1, w. - 37.5). The average annual growth rate is 2.0 (m -2.4, w. -1.9).
1185 patients died from ROC. M. - 526 (44.4%), w. - 659 (55.6%). The average age is 67.6 years (m - 67.2, w. - 67.7). The standardized indicator averaged 5.7 (m.-6.2, w. -5.3) per 100 000 population. The averaged last 10-year indicator, 6.5 compared to 5.8, was the first to grow by 1.12 times (m -7.1 and w. - 5.3 increased 1.3-fold, w.-5.6 and 4,8 grew in 1.16 times). The figure for men is 1.16 times higher than for women. The increase in mortality in both sexes is 12.1 (m. - 33.9, w.- 20.8 m). The average annual growth rate is 1.2 (m. -1.6, w. -1.1).
Active detectability of ROC is 0.7% on average. Morphological verification of the diagnosis 79.4%. Detection of ROC in the I-II stage was 41.4%, III - 29.2% and IV - 29.4%. In the 1 st ten-year period, the indicator of the I-II stage was 18.1%, the second - 38.5% increased 2.1 times. Stage III - 40.0% and 37.1%, stage IV - 41.7% and 29.8% decrease in 1.3 and 1.4 times, respectively. The prevalence of ROC is on the average 56.2 per 100 000 population. The lethality for the 1st year is on the average 32.3 (in the first 10-year period - 36.2, the second - 28.4, 1.3 times less). The proportion of patients who completed special treatment averaged 53.0%. Surgical 56.0%, combined - 44.0%. Survival of 5 years or more on average - 45.5% (in the first 10 years, 41.7, the second - 47.7, 1.4 times more). Out of 263 cases of deaths from ROC from 2007-2011, Up to a year 45,7% lived, 1-3 years - 26,4%, 3-5 years - 5,9%, 5 years and more - 22,0%.
Conclusion: The incidence and mortality of ROC in the republic are growing. The indicator of active detection of patients is extremely low. The neglect is high. Survival is 5 years and lower. Endoscopic screening of the population at risk for ROC is necessary, increasing oncologic alertness and activating anticancer advocacy.