Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs

Governmental surveillance system of healthcare-associated infection in Brazil

Objective: This study aimed to describe the structure of governmental surveillance systems for Healthcare Associated Infection (HAI) in the Brazilian Southeastern and Southern States. Method: A cross-sectional, descriptive and exploratory study, with data collection by means of two-phases: characterization of the healthcare structure and of the HAI surveillance system. Results: The governmental teams for prevention and control of HAI in each State ranged from one to six members, having at least one nurse. All States implemented their own surveillance system. The information systems were classified into chain (n=2), circle (n=4) or wheel (n=1). Conclusion: Were identified differences in the structure and information flow from governmental surveillance systems, possibly limiting a nationwide standardization. The present study points to the need for establishing minimum requirements in public policies, in order to guide the development of HAI surveillance systems

Gauge-independent MS‾\overline{MS} renormalization in the 2HDM

We present a consistent renormalization scheme for the CP-conserving Two-Higgs-Doublet Model based on $\overline{MS}$ renormalization of the mixing angles and the soft-$Z_2$-symmetry-breaking scale $M_{sb}$ in the Higgs sector. This scheme requires to treat tadpoles fully consistently in all steps of the calculation in order to provide gauge-independent $S$-matrix elements. We show how bare physical parameters have to be defined and verify the gauge independence of physical quantities by explicit calculations in a general $R_{\xi}$-gauge. The procedure is straightforward and applicable to other models with extended Higgs sectors. In contrast to the proposed scheme, the $\overline{MS}$ renormalization of the mixing angles combined with popular on-shell renormalization schemes gives rise to gauge-dependent results already at the one-loop level. We present explicit results for electroweak NLO corrections to selected processes in the appropriately renormalized Two-Higgs-Doublet Model and in particular discuss their scale dependence.Comment: 52 pages, PDFLaTeX, PDF figures, JHEP version with Eq. (5.23) correcte

Tree amplitudes and color decomposition in broken SU(2)

We propose a color decomposition for general tree amplitudes in a SU(2) gauge theory which is spontaneously broken via the Higgs mechanism. Working in the unitary gauge, we construct color-ordered amplitudes by explicitly presenting a set of color-ordered Feynman rules. Those primitive amplitudes are gauge-invariant, and they preserve perturbative unitarity in the high-energy limit. Serving as building blocks of color-dressed tree amplitudes, they allow for efficient evaluation of tree-level scattering amplitudes involving gauge bosons and the Higgs boson via the Berends-Giele recursion relations for color-ordered currents. We demonstrate the efficiency of this computational scheme by calculating on-shell amplitudes for scattering of five, six and nine W-bosons in the limit of vanishing Weinberg angle.Comment: 31 pages, 11 figure

Scattering AMplitudes from Unitarity-based Reduction Algorithm at the Integrand-level

SAMURAI is a tool for the automated numerical evaluation of one-loop corrections to any scattering amplitudes within the dimensional-regularization scheme. It is based on the decomposition of the integrand according to the OPP-approach, extended to accommodate an implementation of the generalized d-dimensional unitarity-cuts technique, and uses a polynomial interpolation exploiting the Discrete Fourier Transform. SAMURAI can process integrands written either as numerator of Feynman diagrams or as product of tree-level amplitudes. We discuss some applications, among which the 6- and 8-photon scattering in QED, and the 6-quark scattering in QCD. SAMURAI has been implemented as a Fortran90 library, publicly available, and it could be a useful module for the systematic evaluation of the virtual corrections oriented towards automating next-to-leading order calculations relevant for the LHC phenomenology.Comment: 35 pages, 7 figure

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001–14: a case only analysis

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18–89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001–14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001–14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53–1·70; fully adjusted OR 1·45, 95% CI 1·38–1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22–1·30; fully adjusted OR 1·18, 1·14–1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2–49·5) and lowest for women who were white with university education (29·4%, 28·2–30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%–17·2% in 1970–74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50–69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa

Ethnoracial and social trends in breast cancer staging at diagnosis in Brazil, 2001–14: a case only analysis

Background: Policies for early detection of breast cancer, including clinical breast examinations and mammographic screening, were introduced in Brazil in 2004, but their effect on disease stage at diagnosis is unclear. We aimed to assess whether these policies have led to a decrease in the prevalence of late-stage breast cancer at diagnosis. Methods: In this case only analysis, using an anonymised nationwide hospital based-cancer registry network, we identified women aged 18–89 years who had been diagnosed with an invasive breast cancer in Brazil during 2001–14. We extracted individual patient-level data on patient demographics, tumour variables, and health-care provider variables for the centre where the patient was diagnosed. Our objectives were to estimate the prevalence of late-stage breast cancer (TNM stage III or IV) at diagnosis overall, across age groups, and by ethnoracial and social strata (ie, self-reported ethnoracial group, as white, black, brown, Asian, or Indigenous, and educational level, marital status, and region of residence) across the study period, and compare these estimates with international data from high-income countries (Norway and the USA). We used logistic regression to estimate odds ratios (ORs) for late-stage versus early-stage (TNM stage I or II) breast cancer at diagnosis in relation to relevant exposures, either minimally adjusted (for age, year of diagnosis, and region of residence) or fully adjusted (for all patient, tumour, and health-care provider variables). Findings: We identified 247 719 women who were diagnosed with invasive breast cancer between Jan 1, 2001, and Dec 31, 2014, with a mean age at diagnosis of 55·4 years (SD 13·3), of whom 36·2% (n=89 550) identified as white, 29·8% (n=73 826) as black or brown, and 0·7% (n=1639) as Asian or Indigenous. Prevalence of late-stage breast cancer at diagnosis remained high throughout 2001–14, at approximately 40%, was inversely associated with educational level (p value for linear trend <0·0001), and was higher for women who identified as black (minimally adjusted OR 1·61, 95% CI 1·53–1·70; fully adjusted OR 1·45, 95% CI 1·38–1·54) and brown (minimally adjusted OR 1·26, 95% CI 1·22–1·30; fully adjusted OR 1·18, 1·14–1·23) than those who identified as white. The predicted prevalence of late-stage cancer at diagnosis was highest for women who were black or brown with little or no formal education (48·8%, 95% CI 48·2–49·5) and lowest for women who were white with university education (29·4%, 28·2–30·6), but both these prevalences were higher than that of all women diagnosed with breast cancer in Norway before the introduction of mammography screening (ie, 16·3%, 95% CI 15·4%–17·2% in 1970–74). Similar ethnoracial and social patterns emerged in analyses restricted to the age group targeted by screening (50–69 years). Interpretation: The persistently high prevalence of late-stage breast cancer at diagnosis across all ethnoracial and social strata in Brazil, although more substantially among the most disadvantaged populations, implies that early detection policies might have had little effect on breast cancer mortality so far, and highlights the need to focus primarily on timely diagnosis of symptomatic breast cancer rather than on screening for asymptomatic disease. Funding: Newton Fund, Research Councils UK, and Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa