Role of the Metal Center in the Ethylene Polymerization Promoted by Group 4 Complexes Supported by a Tetradentate [OSSO]-Type Bis(phenolato) Ligand

ACS Catalysis ◽  
2011 ◽  
Vol 1 (11) ◽  
pp. 1460-1468 ◽  
Author(s):  
Massimo Mella ◽  
Lorella Izzo ◽  
Carmine Capacchione
Keyword(s):  
Ethylene Polymerization ◽  
Metal Center ◽  
Group 4

Role of metal center and coordination environment in M-(Z)-N-((E)-pyridin-2-ylmethylene)isonicotinohydrazonate (M = LaIII, ZnII, CdII or HgII) catalyzed cyanosilylation of aldehydes

Polyhedron ◽  
2021 ◽  
Vol 209 ◽  
pp. 115453
Author(s):  
Fatali E. Huseynov ◽  
Ghodrat Mahmoudi ◽  
Sevinc R. Hajiyeva ◽  
Nazim T. Shamilov ◽  
Fedor I. Zubkov ◽  
...  
Keyword(s):  
Metal Center ◽  
Coordination Environment

Elucidating the Key Role of Phosphine−Sulfonate Ligands in Palladium-Catalyzed Ethylene Polymerization: Effect of Ligand Structure on the Molecular Weight and Linearity of Polyethylene

ACS Catalysis ◽  
2016 ◽  
Vol 6 (9) ◽  
pp. 6101-6113 ◽  
Author(s):  
Ryo Nakano ◽  
Lung Wa Chung ◽  
Yumiko Watanabe ◽  
Yoshishige Okuno ◽  
Yoshikuni Okumura ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Ethylene Polymerization ◽  
Ligand Structure ◽  
Palladium Catalyzed

TMOD-26. MYC OVEREXPRESSION AND SMARCA4 LOSS IN GRANULE CELL PRECURSORS COOPERATE TO DRIVE MEDULLOBLASTOMA FORMATION IN MICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi221-vi221
Author(s):  
Carolin Göbel ◽  
Dörthe Holdhof ◽  
Melanie Schoof ◽  
Catena Kresbach ◽  
Ulrich Schüller
Keyword(s):  
Granule Cell ◽  
Clinical Course ◽  
Tumor Development ◽  
Tumor Formation ◽  
Human Group ◽  
Group 4 ◽  
Small Cohort ◽  
Group 3 ◽  
Granule Cell Precursors

Abstract Mutations in SMARCA4 are frequently identified in medulloblastoma, the most common pediatric malignant brain tumor. However, the functional significance of these mutations and their suitability as a therapeutic target remain largely unclear. Medulloblastomas are divided into 4 subgroups according to their localization, molecular biology, and clinical course: WNT, SHH, Group 3, and Group 4. Group 3 medulloblastomas are associated with the poorest outcome and frequently show amplifications of the oncogene MYC. Additionally, SMARCA4 is mutated in around 15 % of cases. The few mouse models developed for this entity so far all involve the overexpression of MYC, mostly in combination with other drivers. However, none of these models include alterations in Smarca4. In our approach, we combined an overexpression of MYC with a loss of SMARCA4 in granule cell precursors, which successfully induced tumor formation in mice. For this purpose, granule cell precursors were isolated from 7-day-old Math1-creER T2 ::Smarca4 fl/fl pups after tamoxifen induced loss of SMARCA4. MYC overexpression was achieved by lentiviral transduction and transduced cells were transplanted into immunodeficient CD1 nu/nu mice. Preliminary results within a small cohort showed tumor formation in 5/19 transplanted mice (26 %) after 6 months. Immunohistochemically, tumors all stained negative for SMARCA4. In a next step, additional cohorts will elucidate if tumor development is indeed accelerated by or even dependent on the loss of SMARCA4. Additionally, the neoplastic potential of tumor cells will be verified with the aid of secondary recipient mice. To evaluate to what extent the generated tumors are comparable to human Group 3 medulloblastomas, tumors will be extensively analyzed on a morphological, transcriptional, and epigenetic level. Altogether, we hope to establish a suitable mouse model for SMARCA4 mutated Group 3 medulloblastoma that will help to elucidate the role of SMARCA4 in tumor development and to identify new therapeutic targets.

P5392Epicardium derived cells promote sympathetic ganglionic outgrowth towards myocardium in vitro

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Ge ◽  
A M Smits ◽  
J C Van Munsteren ◽  
T Van Herwaarden ◽  
A M D Vegh ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Autonomic Innervation ◽  
Cardiac Damage ◽  
Group 4 ◽  
Group 3 ◽  
Cervical Ganglia ◽  
Group 2 ◽  
Group 1

Abstract Background The autonomic nerve system is essential to maintain homeostasis in the body. In the heart, autonomic innervation is important for adjusting the physiology to the continuously changing demands such as stress responses. After cardiac damage, excessive neurite outgrowth, referred to as autonomic hyperinnervation, can occur which is related to ventricular arrhythmias and sudden cardiac death. The cellular basis for this hyperinnervation is as yet unresolved. Here we hypothesize a role for epicardium derived cells (EPDCs) in stimulating sympathetic neurite outgrowth. Purpose To investigate the potential role of adult EPDCs in promoting sympathetic ganglionic outgrowth towards adult myocardium. Method Fetal murine superior cervical ganglia were dissected and co-cultured with activated adult mesenchymal epicardium-derived cells (EPDCs) or/and adult myocardium in a 3D collagen gel culture system. Four experiment groups were included: Group 1: Vehicle cultures (ganglia cultured without EPDC/myocardium) (n=48); Group 2: ganglia co-cultured with EPDCs (n=38); Group 3: ganglia co-cultured with myocardium (n=95); and group 4: ganglia co-cultured with both EPDCs and myocardium (n=96). The occurrence of neurite outgrowth was assessed in each group. The density of neurites that showed directional sprouting (i.e. sprouting towards myocardium) was assessed as well with a semi-automatic quantification method. Finally, sub-analyses were made by taking gender into account. Results Cervical ganglia cultured with EPDCs alone (group 2) showed increased neurite outgrowth compared to vehicle cultures (group 1), however the neurites did not show directional sprouting towards EPDCs. When co-cultured with myocardium (group 3), directional neurite outgrowth towards myocardium was observed. Compared to the ganglia-myocardium co-cultures, directional outgrowth was significantly increased in co-cultures combining myocardium and EPDCs (group 4), and the neurite density was also significantly augmented. Comparison between males and female ganglia demonstrated that more neurite outgrowth occurred in female-derived ganglia than in male-derived ganglia under the same co-culture conditions. Conclusion Activated adult EPDCs promote sympathetic ganglionic outgrowth in vitro. Sex differences exist in the response of ganglia to EPDCs, and female-derived ganglia appear more sensitive to EPDC-signalling. Results support a role of EPDCs in cardiac autonomic innervation and open avenues for exploring of their role in ventricular hyperinnervation after cardiac damage.

Experimental model of posttraumatic syringomyelia: the role of adhesive arachnoiditis in syrinx formation

1994 ◽  
Vol 80 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Ki Hong Cho ◽  
Yoshinobu Iwasaki ◽  
Hiroyuki Imamura ◽  
Kazutoshi Hida ◽  
Hiroshi Abe
Keyword(s):  
Normal Saline ◽  
Subarachnoid Space ◽  
Saline Solution ◽  
Traumatic Injury ◽  
Content Type ◽  
Group 4 ◽  
Kaolin Injection ◽  
Group 3 ◽  
Group 2

✓ An experimental model was devised to elucidate the role of spinal blockade in posttraumatic syringomyelia. Thirty-eight Japanese White rabbits, each weighing about 3 kg, were used in this study. The animals were divided into four groups: in Group 1, eight animals received traumatic injury only; in Group 2, 12 animals received traumatic injury following injection of 100 mg kaolin suspended in 1 cc normal saline solution into the subarachnoid space at the site of trauma; in Group 3, nine animals received traumatic injury following injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space at the site of trauma; and in Group 4, nine animals without traumatic injury received an injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid space. The subjective criteria for syrinx formation were the presence of a definite round cyst having a smooth margin and an upper or lower extension of more than 2 cm from the injured site. Syrinx formation was seen in 12.5% (one of eight rabbits) in Group 1, 41.7% (five of 12 animals) in Group 2, 55.5% (five of nine rabbits) in Group 3 and 0% (none of nine animals) in Group 4 (p < 0.05). There was a tendency for the combined trauma/kaolin injection groups to be more prone to develop a syrinx. In the kaolin injection only group (Group 4), no animal showed a definite cyst or an extending cavity during the experimental period. The results suggest that kaolin enhances the extension of multiple small cavities that have already formed at the time of initial injury. The difference between the frequency of syrinx formation and the time of survival was statistically significant well beyond the 0.05% level. The overall difference, relating to the frequency of syrinx development, group, and duration of survival, was also statistically significant. In summary, subarachnoid block secondary to adhesive arachnoiditis is important in initiating the extension of the syringomyelia cavity.

Diaphragmatic failure during group B streptococcal sepsis in piglets: the role of thromboxane A2

1995 ◽  
Vol 78 (2) ◽  
pp. 491-498 ◽  
Author(s):  
T. D. Murphy ◽  
R. L. Gibson ◽  
T. A. Standaert ◽  
D. E. Woodrum
Keyword(s):  
Group B Streptococcus ◽  
Thromboxane A2 ◽  
Treated Group ◽  
Arachidonic Acid Metabolism ◽  
Group 4 ◽  
Group 2 ◽  
Txa2 Receptor Antagonist ◽  
Group B ◽  
Spontaneously Breathing

Group B Streptococcus (GBS) causes an impairment of diaphragmatic pressure generation (Pdi) in 2-wk-old piglets, whereas 4-wk-old piglets are unaffected. In this study, we examined the effect on 4-wk-old piglets of a higher dose of GBS than previously utilized. We sought to determine whether an eicosanoid product of arachidonic acid metabolism accounted for the decrease in Pdi during GBS infusion and whether thromboxane A2 (TxA2) is the putative eicosanoid mediator of decreased Pdi during GBS infusion. Measuring Pdi during phrenic nerve stimulation, we studied four groups of anesthetized spontaneously breathing 4-wk-old piglets. Group 1 (GBS) was infused with live GBS, which caused a decrease in Pdi by 1 h at 20-, 30-, 50-, and 100-Hz stimulation frequencies. Group 2 [GBS + indomethacin (Indo)] was pretreated with Indo before GBS infusion. In the GBS + Indo group, Pdi did not decrease throughout 4 h of GBS infusion. Because Indo proved to be protective of Pdi during GBS infusion, we examined the role of TxA2, the only eicosanoid present at 1 h in the serum of GBS-infused piglets. Group 3 was infused with the TxA2 analogue U-46619 only for 1 h. Group 4 was treated with the TxA2-receptor antagonist SQ-29548 before and concomitant with GBS infusion for 1 h; the SQ-29548 was then discontinued, and GBS was continued for 1 h more. In the U-46619-infused group, Pdi decreased at 1 h, and in the SQ-29548-treated group, Pdi did not decrease during GBS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Preclinical Models of Craniospinal Irradiation for Medulloblastoma

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 133 ◽  
Author(s):  
Jennifer L. Stripay ◽  
Thomas E. Merchant ◽  
Martine F. Roussel ◽  
Christopher L. Tinkle
Keyword(s):  
Small Animal ◽  
Craniospinal Irradiation ◽  
Tumor Control ◽  
Preclinical Models ◽  
Treatment Interventions ◽  
Leptomeningeal Seeding ◽  
Group 4 ◽  
Pediatric Medulloblastoma ◽  
Group 3

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors.

Impact of cytoreductive nephrectomy on disease-specific survival (DSS) in the cytokine and targeted therapy eras: Age- and TNM-stage matched analysis of SEER data.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4579-4579
Author(s):  
Rebecca A. Nelson ◽  
Nicholas J. Vogelzang ◽  
Sumanta Kumar Pal
Keyword(s):  
Targeted Therapy ◽  
Clear Cell ◽  
Tnm Stage ◽  
Cytoreductive Nephrectomy ◽  
Clinicopathologic Characteristics ◽  
Group 4 ◽  
Seer Data ◽  
N Stage ◽  
Prospective Trials

4579 Background: The role of cytoreductive nephrectomy (CN) for patients with mRCC was well-defined in the cytokine era. However, its role is controversial in the era of targeted therapies. Methods: The Survival, Epidemiology, and End Results (SEER) Database was queried to compare the relative benefit of CN in the cytokine era (defined as 1992-2004) as compared to the targeted therapy era (defined as 2005-2009). Patients with mRCC and clear cell, papillary or chromophobe histology were identified, and divided into cohorts with and without CN. Within each category, patients diagnosed during the cytokine era were matched by age and TNM stage to patients diagnosed during the targeted therapy era. Associations between clinicopathologic characteristics and DSS were explored through univariate and multivariate analyses. Results: Amongst matched pts who had received CN (n=2,218), no significant differences in age, gender, race, histology (clear cell v non-clear cell), T-stage, or N-stage were observed. Median DSS was superior in those patients diagnosed during the targeted therapy era as compared to the cytokine era (22 mos v 17 mos, P<0.0001). On multivariate analysis including the aforementioned clinicopathologic variables and DSS, diagnosis during the targeted therapy era was an independent predictor of improved survival amongst patients who had received CN (HR 0.78, 95%CI 0.70-0.87; P<0.0001). Amongst matched pts who had not received CN (n=4,214), there were no differences in clinicopathologic characteristics. Median DSS was similar in patients diagnosed during the targeted therapy era as compared to the cytokine era within this group (4 mos for each; P=NS). Conclusions: Patients who received CN during the targeted therapy era had a superior DSS as compared to patients who received the procedure during the cytokine era. In contrast, patients who had not received CN had a similar DSS across both time periods. While prospective trials mature (i.e., CARMENA and EORTC 30073), these data support the continued use of CN in the context of targeted agents.

A Discrimination Based on Punishment

1952 ◽  
Vol 4 (1) ◽  
pp. 27-45 ◽  
Author(s):  
James A. Dinsmoor
Keyword(s):  
The Other ◽  
Control Group ◽  
Experimental Session ◽  
Group 4 ◽  
White Rats ◽  
The Difference ◽  
Avoidance Reactions ◽  
Experimental Group ◽  
Rate Of Response

Twelve white rats learned to press a bar or lever when this act was intermittently followed by pellets of food. Once a stable rate of pressing had been established, the animals were subjected to electric shock as a punishment for each response during alternate five minute periods within the experimental session. A difference in rates during the safe and punished phases was manifested both by the experimental group (8 rats), who were provided with a light as a signal when it was safe to respond, and also, contrary to expectation, by the control group (4 rats), who continued in darkness throughout the session. The differential responding by the control group was greatly reduced, however, when the duration of each phase was reduced from five minutes to one. The investigation was then continued to determine the role of some of the other factors in the situation. Increasing the severity of the shock increased the difference between the light and the dark rates. Withholding the pellets of food reduced the overall rates but did not affect the light-dark discrimination. Withholding the shock, on the other hand, permitted an increase in rate and caused the animals to lose their discrimination; when food had previously been withheld, however, so that the rate of response was relatively low, this deterioration in the discrimination was not as rapid as before. Restoration of the discrimination training under a lower hunger drive confirmed the finding that the formation of the discrimination was quite rapid and showed that the level of drive did not affect the proportionality between the rates in the light and in the darkness. These findings were interpreted by comparing the current procedure with those previously used in studies of avoidance reactions and conflict.

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