The prognostic impact of treatment centralization in patients with testicular germ cell tumors: analysis of hospital-based cancer registry data in Japan.

BACKGROUND: To identify the prognostic impact of treatment centralization in patients with testicular germ cell tumors (TGCT). METHODS: We used a hospital-based cancer registry data in Japan to extract seminoma and non-seminoma cases that were diagnosed in 2013, histologically confirmed, and received the first course of treatment. To compare the 5-years overall survival (OS) rates of patients stratified by institutional care volume, we performed a Cox proportional hazards regression analysis using inverse probability of treatment weighting (IPTW) method to adjust patient backgrounds. RESULTS: A total of 1767 TGCT patients were identified. The 5-years OS rates for stage II and III TGCT patients treated at low-volume institutions (< 7 cases) were significantly worse than high-volume institutions (≥ 7 cases) (91.2% vs. 83.4%, p = 0.012). Histological stratification revealed that 5-year OS rates for stage II and III seminoma patients in the low-volume group were significantly worse than the high-volume group (93.5% vs. 84.5%, p = 0.041). Multivariate OS analysis using an IPTW-matched cohort showed that institutional care volume was an independent prognostic factor (hazard ratio 2.13 [95% confidence interval: 1.23-3.71], p = 0.0072). CONCLUSION: Our results indicate that stage II and III TGCT patients experience lower survival rates at low-volume institutions and would benefit from treatment centralization.

Neutral and Cationic Molybdenum Imido Alkylidene Cyclic Alkyl Amino Carbene (CAAC) Complexes for Olefin Metathesis.

The first neutral and cationic Mo imido alkylidene cyclic alkyl amino carbene (CAAC) complexes of the general formulae [Mo(N-Ar)(CHCMe2 Ph)(X)2 (CAAC)] and [Mo(N-Ar)(CHCMe2 Ph)(X)(CAAC)][B(ArF )4 ] (X=Br, Cl, OTf, OC6 F5 ; CAAC=1-(2,6-iPr2 -C6 H3 )-3,3,5,5-tetramethyltetrahydropyrrol-2-ylidene) have been synthesized from molybdenum imido bishalide alkylidene DME precursors. Different combinations of the imido and "X" ligands have been employed to understand synthetic peculiarities. Selected complexes have been characterized by single-crystal X-ray analysis. Due to the pronounced σ-donor/π-acceptor characteristics of CAACs, the corresponding neutral and cationic molybdenum imido alkylidene CAAC complexes do not require the presence of stabilizing donor ligands such as nitriles. Calculations on the PBE0-D3BJ/def2-TZVP level for PBE0-D3BJ/def2-SVP optimized geometries revealed partial charges at molybdenum similar to the corresponding molybdenum imido alkylidene N-heterocyclic carbene (NHC) complexes with a slightly higher polarization of the molybdenum alkylidene bond in the CAAC complexes. All cationic complexes have been tested in olefin metathesis reactions and showed improved activity compared to the analogous NHC complexes for hydrocarbon-based substrates, allowing for turnover numbers (TONs) up to 9500 even at room temperature. Some Mo imido alkylidene CAAC complexes are tolerant towards functional groups like thioethers and sulfonamides.

Cationic molybdenum oxo alkylidenes stabilized by N-heterocyclic carbenes: from molecular systems to efficient supported metathesis catalysts.

Cationic d0 group 6 olefin metathesis catalysts have been recently shown to display in most instances superior activity in comparison to their neutral congeners. Furthermore, their catalytic performance is greatly improved upon immobilization on silica. In this context, we have developed the new family of molecular cationic molybdenum oxo alkylidene complexes stabilized by N-heterocyclic carbenes of the general formula [Mo(O)(CHCMe3)(IMes)(OR)[X-]] (IMes = 1,3-dimesitylimidazol-2-ylidene; R = 1,3-dimesityl-C6H3, C6F5; X- = B(3,5-(CF3)2C6H3)4 -, B(ArF)4, tetrakis(perfluoro-t-butoxy)aluminate (PFTA)). Immobilization of [Mo(O)(CHCMe3)(IMes)(O-1,3-dimesityl-C6H3)+B(ArF)4 -] on silica via surface organometallic chemistry yields an active alkene metathesis catalyst that shows the highest productivity towards terminal olefins amongst all existing molybdenum oxo alkylidene catalysts.

Clinicopathological features of adrenal malignancies: Analysis of hospital-based cancer registry data in Japan.

OBJECTIVE: To identify the clinicopathological features of adrenal malignancies and analyze the prognoses of patients with adrenal cortical carcinoma (ACC) and malignant pheochromocytoma (MPCC). PATIENTS AND METHODS: We used a hospital-based cancer registry data in Japan to extract cases of adrenal malignancies that were histologically confirmed, diagnosed, and initially treated from 2012-2015. For survival analysis, we used data from the 2008-2009 cohort to estimate 5-year overall survival (OS) by the Kaplan-Meier method. RESULTS: A total of 989 adrenal malignancies were identified in the 2012-2015 cohort. The most common histologies were ACC (26.4%), diffuse large B-cell lymphoma (DLBCL; 25.4%), neuroblastoma (22.2%), and MPCC (11.9%). While most ACC and MPCC patients were in their 60s, DLBCL patients accounted for 61.5% of adrenal malignancies in the over-70 cohort. Among ACC patients with clinical staging data, 46.3% of patients were stage IV. Although surgery was a chief strategy for all stages, younger patients tended to receive combination therapy, including surgery and chemotherapy or hormone therapy. In the 2008-2009 cohort, the 5-year OS rates of ACC (n = 49) and MPCC (n = 23) patients were 56.2% and 86.4% while ACC patients without surgery had 1- and 2-year OS rates of 25.0% and 12.5%. CONCLUSION: In Japan, DLBCL accounted for the majority of adrenal malignancies in older patients. Despite advanced staging, ACC patients were mainly treated with surgery and their prognosis was not satisfactory. Such epidemiological data may be useful in considering initial management strategies.

Interstitial Granulomatous Drug Reaction to Ustekinumab.

Interstitial granulomatous drug reaction (IGDR) is a distinct inflammatory process that often presents as annular, violaceous plaques distributed on the extremities, proximal trunk, and intertriginous areas. The list of drugs implicated for inciting IGDR is growing, but most prominently includes ACE inhibitors, antihistamines, beta-blockers, antidepressants, and anticonvulsants. Ustekinumab is a human monoclonal antibody that targets inflammatory cytokines IL-12 and IL-23 and has been have shown to be effective in treating IGDR. However, we present a case that suggests ustekinumab can also act as an inciting agent for IGDR.

Olefin-Surface Interactions: A Key Activity Parameter in Silica-Supported Olefin Metathesis Catalysts.

Molecularly defined and classical heterogeneous Mo-based metathesis catalysts are shown to display distinct and unexpected reactivity patterns for the metathesis of long-chain α-olefins at low temperatures (<100 °C). Catalysts based on supported Mo oxo species, whether prepared via wet impregnation or surface organometallic chemistry (SOMC), exhibit strong activity dependencies on the α-olefin chain length, with slower reaction rates for longer substrate chain lengths. In contrast, molecular and supported Mo alkylidenes are highly active and do not display such dramatic dependence on the chain length. State-of-the-art two-dimensional (2D) solid-state nuclear magnetic resonance (NMR) spectroscopy analyses of postmetathesis catalysts, complemented by Fourier transform infrared (FT-IR) spectroscopy and molecular dynamics calculations, evidence that the activity decrease observed for supported Mo oxo catalysts relates to the strong adsorption of internal olefin metathesis products because of interactions with surface Si-OH groups. Overall, this study shows that in addition to the nature and the number of active sites, the metathesis rates and the overall catalytic performance depend on product desorption, even in the liquid phase with nonpolar substrates. This study further highlights the role of the support and active site composition and dynamics on activity as well as the need for considering adsorption in catalyst design.

CXCL12 Retargeting of an Oncolytic Adenovirus Vector to the Chemokine CXCR4 and CXCR7 Receptors in Breast Cancer.

Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant progress has been made in developing targeted therapies for breast cancer, advanced breast cancer continues to have high mortality, with poor 5-year survival rates. Thus, current therapies are insufficient in treating advanced stages of breast cancer; new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We showed that the modified virus targets and infects CXCR4- and CXCR7-overexpressing breast cancer cells more efficiently than a wild-type control vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the results of this study demonstrate the feasibility of retargeting adenovirus vectors to chemokine receptor-positive tumors.

Cationic Group VI Metal Imido Alkylidene N-Heterocyclic Carbene Nitrile Complexes: Bench-Stable, Functional-Group-Tolerant Olefin Metathesis Catalysts.

Despite their excellent selectivities and activities, Mo-and W-based catalysts for olefin metathesis have not gained the same widespread use as Ru-based systems, mainly due to their inherent air sensitivity. Herein, we describe the synthesis of air-stable cationic-at-metal molybdenum and tungsten imido alkylidene NHC nitrile complexes. They catalyze olefin metathesis reactions of substrates containing functional groups such as (thio-) esters, (thio-) ethers and alcohols without the need for prior activation, for example, by a Lewis acid. The presence of a nitrile ligand was found to be essential for their stability towards air, while no decrease in activity and productivity could be observed upon coordination of a nitrile. Variations of the imido and anionic ligand revealed that alkoxide complexes with electron-withdrawing imido ligands offer the highest reactivities and excellent stability compared to analogous triflate and halide complexes.

SurA is a cryptically grooved chaperone that expands unfolded outer membrane proteins.

The periplasmic chaperone network ensures the biogenesis of bacterial outer membrane proteins (OMPs) and has recently been identified as a promising target for antibiotics. SurA is the most important member of this network, both due to its genetic interaction with the ß-barrel assembly machinery complex as well as its ability to prevent unfolded OMP (uOMP) aggregation. Using only binding energy, the mechanism by which SurA carries out these two functions is not well-understood. Here, we use a combination of photo-crosslinking, mass spectrometry, solution scattering, and molecular modeling techniques to elucidate the key structural features that define how SurA solubilizes uOMPs. Our experimental data support a model in which SurA binds uOMPs in a groove formed between the core and P1 domains. This binding event results in a drastic expansion of the rest of the uOMP, which has many biological implications. Using these experimental data as restraints, we adopted an integrative modeling approach to create a sparse ensemble of models of a SurA•uOMP complex. We validated key structural features of the SurA•uOMP ensemble using independent scattering and chemical crosslinking data. Our data suggest that SurA utilizes three distinct binding modes to interact with uOMPs and that more than one SurA can bind a uOMP at a time. This work demonstrates that SurA operates in a distinct fashion compared to other chaperones in the OMP biogenesis network.

Mechanistic studies of cytotoxic activity of the mesoionic compound MIH 2.4Bl in MCF-7 breast cancer cells.

In the present study, the cytotoxic effects of a 1,3-thiazolium-5-thiolate derivative of a mesoionic compound, MIH 2.4Bl, were assessed in the MCF-7 breast cancer cell line. The cytotoxic effects of MIH 2.4Bl were determined using a crystal violet assay. Using a dose-response curve, the IC50 value of MIH 2.4Bl was determined to be 45.8±0.8 µM. Additionally, the effects of MIH 2.4Bl on mitochondrial respiration were characterized using oxygen consumption rate analysis. Treating MCF-7 cells with increasing concentrations of MIH 2.4Bl resulted in a significant reduction in all mitochondrial respiratory parameters compared with the control cells, indicative of an overall decrease in mitochondrial membrane potential. The induction of autophagy by MIH 2.4Bl was also examined by measuring changes in the expression of protein markers of autophagy. As shown by western blot analysis, treatment of MCF-7 cells with MIH 2.4Bl resulted in increased protein expression levels of Beclin-1 and ATG5, as well as an increase in the microtubule-associated protein 1A/1B light chain 3B (LC3B)-II to LC3B-I ratio compared with the control cells. Microarray analysis of changes in gene expression following MIH 2.4Bl treatment demonstrated 3,659 genes exhibited a fold-change ≥2. Among these genes, 779 were up-regulated, and 2,880 were down-regulated in cells treated with MIH 2.4Bl compared with the control cells. Based on the identity of the transcripts and fold-change of expression, six genes were selected for verification by reverse transcription-quantitative (RT-q)PCR; activating transcription factor 3, acidic repeat-containing protein, heparin-binding EGF-like growth factor, regulator of G-protein signaling 2, Dickkopf WNT signaling pathway inhibitor 1 and adhesion molecule with Ig like domain 2. The results of RT-qPCR analysis of RNA isolated from control and MIH 2.4Bl treated cells were consistent with the expression changes identified by microarray analysis. Together, these results suggest that MIH 2.4Bl may be a promising candidate for treating breast cancer and warrants further in vitro and in vivo investigation.

Domain interactions determine the conformational ensemble of the periplasmic chaperone SurA.

SurA is thought to be the most important periplasmic chaperone for outer membrane protein (OMP) biogenesis. Its structure is composed of a core region and two peptidylprolyl isomerase domains, termed P1 and P2, connected by flexible linkers. As such these three independent folding units are able to adopt a number of distinct spatial positions with respect to each other. The conformational dynamics of these domains are thought to be functionally important yet are largely unresolved. Here we address this question of the conformational ensemble using sedimentation equilibrium, small-angle neutron scattering, and folding titrations. This combination of orthogonal methods converges on a SurA population that is monomeric at physiological concentrations. The conformation that dominates this population has the P1 and core domains docked to one another, for example, "P1-closed" and the P2 domain extended in solution. We discovered that the distribution of domain orientations is defined by modest and favorable interactions between the core domain and either the P1 or the P2 domains. These two peptidylprolyl domains compete with each other for core-binding but are thermodynamically uncoupled. This arrangement implies two novel insights. Firstly, an open conformation must exist to facilitate P1 and P2 exchange on the core, indicating that the open client-binding conformation is populated at low levels even in the absence of client unfolded OMPs. Secondly, competition between P1 and P2 binding paradoxically occludes the client binding site on the core, which may serve to preserve the reservoir of binding-competent apo-SurA in the periplasm.

Cytotoxic Activity of the Mesoionic Compound MIH 2.4Bl in Breast Cancer Cell Lines.

In this work, we report the synthesis of a new 1,3-thiazolium-5-thiolate derivative of a mesoionic compound (MIH 2.4Bl) and the characterization of its selective cytotoxicity on a panel of breast cancer cells lines. The cytotoxic effect of MIH 2.4Bl on breast cancer cell lines was determined by XTT and crystal violet assays, flow cytometry analysis, electron microscopy characterization, and terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) apoptosis assays. As determined using XTT cell growth and survival assays, MIH 2.4Bl exhibited growth inhibition activity on most breast cancer cell lines tested, compared with normal human mammary epithelial cells. Three breast cancer cell lines (MCF-7, T-47D, and ZR-75-1) showed a more potent sensitivity index to growth inhibition by MIH 2.4Bl than the other breast cancer cell lines. Interestingly, these 3 cell lines were derived from tumors of Luminal A origin and have ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2) positive expression. Additional analysis of cytotoxicity mediated by MIH 2.4Bl was performed using the MCF-7 cell line. MCF-7 cells displayed both time- and dose-dependent decreases in cell growth and survival, with a maximum cytotoxic effect observed at 72 and 96 hours. The MCF-7 cells were also characterized for cell cycle changes upon treatment with MIH 2.4Bl. Using flow cytometry analysis of cell cycle distribution, a treatment-dependent effect was observed; treatment of cells with MIH 2.4Bl increased the G2/M population to 34.2% compared with 0.1% in untreated (control) cells. Ultrastructural analysis of MFC-7 cells treated with MIH 2.4Bl at 2 different concentrations (37.5 and 75 µM) was performed by transmission electron microscopy. Cells treated with 37.5 µM MIH 2.4Bl showed morphologic changes beginning at 6 hours after treatment, while cells treated with 75 µM showed changes beginning at 3 hours after treatment. These changes were characterized by an alteration of nuclear morphology and mitochondrial degeneration consistent with apoptotic cell death. Results of a TUNEL assay performed on cells treated for 96 hours with MIH 2.4Bl supported the observation of apoptosis. Together, these results suggest that MIH 2.4Bl is a promising candidate for treating breast cancer and support further in vitro and in vivo investigation.

Reversible N-Heterocyclic Carbene-Induced α-H Abstraction in Tungsten(VI) Imido Dialkyl Dialkoxide Complexes.

The first reversible N-heterocyclic carbene (NHC) induced α-H abstraction in tungsten(VI) imido-dialkyl dialkoxide complexes is reported. Treatment of W(NAr)(CH2 Ph)2 (OtBu)2 (Ar=2,6-dichlorophenyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl) with different NHCs leads to the formation of complexes of the type W(NAr)(CHPh)(NHC)(CH2 Ph)(OtBu) in excellent isolated yields of up to 96 %. The highly unusual release of the tert-butoxide ligand as tBuOH in the course of the reaction was observed. The formed alkylidene complexes and tBuOH are in an equilibrium with the NHC and the dialkyl complexes. Reaction kinetics were monitored by 1 H NMR spectroscopy. A correlation between the steric and electronic properties of the NHC and the reaction rates was observed. Kinetics of a deuterium-labeled complex in comparison to its non-deuterated counterpart revealed the presence of a strong primary kinetic isotope effect (KIE) of 4.2, indicating that α-H abstraction is the rate-determining step (RDS) of the reaction.

Regio- and Stereospecific Cyclopolymerization of α,ω-Diynes by Cationic Molybdenum Imido Alkylidene N-Heterocyclic Carbene Complexes.

Both solvent-free and acetonitrile-containing cationic molybdenum imido alkylidene N-heterocyclic carbene (NHC) complexes of the general formula [Mo(NR')(CHCMe2 R)(NHC)(X)+ A- ] (R' = 2,6-Cl2 -C6 H3 , tBu, 2-CF3 -C6 H4 , 2-tBu-C6 H4 , 2,6-iPr2 -C6 H3 , 2,6-Me2 -C6 H3 ; R = Me, Ph; NHC = 1,3-dimesitylimidazol-2-ylidene (IMes), 1,3-di-iPr-imidazol-2-ylidene (IPr), 1,3,5-triphenyl-1,3,4-triazol-2-ylidene); X = CF3 SO3 , C6 F5 O, OCH(CF3 )2 , OC(CF3 )3 , pyrrolide, C6 F5 COO, 2,6-(CF3 )2 -C6 H3 COO; A- = B(ArF )4 - , Al(OC(CF3 )3 )4 - ), have been investigated for their propensity to cyclopolymerize 4,4-disubstituted 1,6-heptadiynes. All metal complexes contain a stereogenic (chiral) metal center, which accounts for the high reactivity and high regioselectivity of insertion (>99%) that are observed for all metal complexes, leading to highly conjugated, α-insertion-derived polyenes that are based on a highly regular polymer backbone and that show absorption maxima close to 600 nm. With the chiral monomer 4-(ethoxycarbonyl)-4-(1S,2R,5S)-(-)-menthoxycarbonyl-1,6-heptadiyne, high syndiospecifity (>99% syndiotactic) is observed. A mechanism explaining the high regio- and stereoselectivity is presented. Thus, α-addition of the monomers proceeds chain-end-controlled trans to the NHC and is preferred over ß-addition through intramolecular Mo-O chelation. Insertion of the monomers entails double inversion at the stereogenic metal center in the course of one complete monomer insertion.

La anticoncepción en la mujer obesa / Contraception in obese women

La creciente prevalencia de mujeres obesas en edad fértil es una crisis de salud pública y social. La anticoncepción es un tema clave en mujeres con obesidad. Las mujeres obesas tienen una actividad sexual similar a las mujeres de peso normal y en ellas se considera que el uso de anticoncepción es menos eficaz, teniendo mayor riesgo de embarazo no deseado. Debido a una variedad de alteraciones del metabolismo, la obesidad es un factor de riesgo cardiovascular que puede aumentar, cuando se combina con la anticoncepción hormonal. Todos estos factores deben considerarse al elegir un método anticonceptivo en una mujer obesa. El objetivo de esta revisión es evaluar el riesgo-beneficio de cada tipo de anticoncepción disponible y la problemática de anticoncepción después de la cirugía bariátrica, proporcionando al médico una guía práctica sobre el uso de píldoras anticonceptivas orales en mujeres obesas

The increasing prevalence of obese women of childbearing age is a public and social health crisis. Contraception is a key issue in women with obesity. Obese women have a sexual activity no different from women of normal weight, and the use of contraception is considered less effective, as there is a higher risk of having an unwanted pregnancy. Due to a variety of metabolic disorders, obesity is a cardiovascular risk factor that can increase when combined with hormonal contraception. All these factors should be considered when choosing a contraceptive method in an obese woman. The objective of this review is to evaluate the risk-benefit of each type of available contraception, and the problem of contraception after bariatric surgery, in order to provide doctors with a practical guide on the use of oral contraceptive pills in obese women

Tumor-Targeting NIRF NanoGUMBOS with Cyclodextrin-Enhanced Chemo/Photothermal Antitumor Activities.

The near-infrared fluorescent (NIRF) dye, IR780, is recognized as a promising theranostic agent and has been widely investigated for imaging, chemotherapeutic, and phototherapeutic applications. However, its poor photostability and nonselective toxicities toward both cancer and normal cells limit its biological applications. Herein, we introduce the use of GUMBOS (a group of uniform materials based on organic salts) developed through counter-anion exchange with IR780 and subsequent nanomaterials (nanoGUMBOS) formed by complexation with cyclodextrin (CD) for enhanced chemo/photothermal therapy. Such CD-based nanoGUMBOS display improved aqueous stability, photostability, and photothermal effects relative to traditional IR780. The examination of in vitro cytotoxicity reveals that CD-based nanoGUMBOS are selectively toxic toward cancer cells and exhibit synergistically enhanced cytotoxicity toward cancer cells upon NIR laser irradiation. Additionally, in vivo NIRF imaging demonstrated selective accumulation of these nanoGUMBOS within the tumor site, indicating tumor-targeting properties. Further in vivo therapeutic study of these CD-based nanoGUMBOS suggests excellent chemo/photothermal antitumor effects. Using these studies, we herein demonstrate a promising strategy, via conversion of IR780 into nanoGUMBOS, that can be used for improved theranostic cancer treatment.

Synthesis, Characterization, and Evaluation of Near-IR Boron Dipyrromethene Bioconjugates for Labeling of Adenocarcinomas by Selectively Targeting the Epidermal Growth Factor Receptor.

A series of five boron dipyrromethene (BODIPY) bioconjugates containing an epidermal growth factor receptor (EGFR)-targeted pegylated LARLLT peptide and/or a glucose or biotin ethylene diamine group were synthesized, and the binding capability of the new conjugates to the extracellular domain of EGFR was investigated using molecular modeling, surface plasmon resonance, fluorescence microscopy, competitive binding assays, and animal studies. The BODIPY conjugates with a LARLLT peptide were found to bind specifically to EGFR, whereas those lacking the peptide bound weakly and nonspecifically. All BODIPY conjugates showed low cytotoxicity (IC50 > 94 µM) in HT-29 cells, both in the dark and upon light activation (1.5 J/cm2). Studies of nude mice bearing subcutaneous human HT-29 xenografts revealed that only BODIPY conjugates bearing the LARLLT peptide showed tumor localization 24 h after intravenous administration. The results of our studies demonstrate that BODIPY bioconjugates bearing the EGFR-targeting peptide 3PEG-LARLLT show promise as near-IR fluorescent imaging agents for colon cancers overexpressing EGFR.

Synthesis and investigation of phthalocyanine-biotin conjugates.

An isothiocyanato-functionalized phthalocyanine (Pc) was synthesized in good yield from the corresponding amine-substituted Pc. This Pc reacted with ethanolamine, biotin hydrazine, and biotin diethylamine under mild conditions (room temperature in DMF or DMSO in the presence of TEA) to produce the corresponding thiourea products in 60-75% yields. All Pcs showed intense Q absorptions in DMF around 677 nm, emissions centered at 683 nm, and fluorescence quantum yields in the range 0.18-0.27. The Pcs were phototoxic to human carcinoma HEp2 cells (IC50 ~ 7 at 1.5 J/cm2) and localized in multiple organelles, including the lysosomes, Golgi and ER. One biotin-Pc conjugate was injected via tail vein into nude mice bearing HT-29 tumors and demonstrated selective localization in the tumor tissue.

Oncolytic Virotherapy for Breast Cancer Treatment.

Breast cancer continues to be a leading cause of mortality among women. While at an early stage, localized breast cancer is easily treated; however, advanced stages of disease continue to carry a high mortality rate. The discrepancy in treatment success highlights that current treatments are insufficient to treat advanced-stage breast cancer. As new and improved treatments have been sought, one therapeutic approach has gained considerable attention. Oncolytic viruses are uniquely capable of targeting cancer cells through intrinsic or engineered means. They come in many forms, mainly from four major virus groups as defined by the Baltimore classification system. These vectors can target and kill cancer cells, and even stimulate immunotherapeutic effects in patients. This review discusses not only individual oncolytic viruses pursued in the context of breast cancer treatment but also the emergence of combination therapies with current or new therapies, which has become a particularly promising strategy for treatment of breast cancer. Overall, oncolytic virotherapy is a promising strategy for increased treatment efficacy for advanced breast cancer and consequently provides a unique platform for personalized treatments in patients.

Can we use robotic surgery for the treatment of pelvic recurrence and locally advanced tumors in gynecological surgery?

Over the past 20 years, feasibility of laparoscopic approaches has been validated in gynecologic surgery. This procedure has specific challenges due its longer learning curve and the limits imposed by the technique. For the surgical treatment of recurrent pelvic cancers or locally advanced tumors, open surgery remains the gold standard for most surgical teams. Robotic assistance could be an interesting alternative. The aim of this study is to present our department's robotic surgical procedures in this specific field and show its feasibility and reproducibility on several patients.