Figure S6 from Optimized EGFR Blockade Strategies in <i>EGFR</i> Addicted Gastroesophageal Adenocarcinomas
Simona CorsoFilippo PietrantonioMaria ApicellaCristina MiglioreDaniela ConticelliAnnalisa PetrelliLaura D’ErricoStefania DurandoDaniel Moya-RullSara E. BellomoStefano UghettoMaurizio DegiuliRossella ReddavidUberto FumagalliStefano De PascaleGiovanni SgroiEmanuele RausaGian Luca BaiocchiSarah MolfinoGiovanni De ManzoniMaria BencivengaSalvatore SienaAndrea Sartore‐BianchiFederica MoranoSalvatore CoralloMichele PrisciandaroMaria Di BartolomeoAnnunziata GloghiniSilvia MarsoniAntonino SottileAnna SapinoCaterina MarchiòÅsa Dahle-SmithZosia MiedzybrodzkaJessica LeeSiraj M. AliJeffrey S. RossBrian M. AlexanderVincent A. MillerRussell PettyAlexa B. SchrockSilvia Giordano
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<p>Supplementary Figure 6_Revised</p>SUMMARY The effects of adrenergic α and β receptor blockade on the thyrotrophin and prolactin responses to TRH were studied in groups of hyperthyroid patients who received either oral propranolol and phenoxybenzamine or intravenous propranolol and rogitine. The flat TSH and prolactin responses to TRH in the untreated hyperthyroid patients were not altered by oral or intravenous adrenergic α and β receptor blockade suggesting that catecholamines do not play a major role in the feedback suppression of TSH and prolactin in hyperthyroidism.
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Abstract Glioblastoma (GBM) is refractory to current T cell-based immunotherapies such as checkpoint blockade. GBM is characterized by extensive infiltration of immunosuppressive macrophages that contribute to the treatment resistance. Here we develop a dual-targeting strategy to synergistically activate tumor-associated macrophages (Mφs), which efficiently overcomes GBM resistance to therapeutic blockade of the PD1 and CTLA4 checkpoints. Consistent with a pro-tumor role of IL-6 in alternative Mφ polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mφs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mφs. Combination of IL-6 inhibition with CD40 stimulation reverses Mφ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models. Notably, this antibody cocktail-based combination immunotherapy with checkpoint blockade almost doubles animal survival in the genetically engineered mouse GBM model and induces complete tumor regression in the GL261 model. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting therapeutic opportunities for GBM.
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Jæger, P.; Grevstad, U.; Henningsen, M. H.; Gottschau, B.; Mathiesen, O.; Dahl, J. B. Author Information
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Lumbar, paravertebral sympathetic block injections with a lidocaine and contrast solution resulted in significant peridural spread of contrast solution. Bilateral, extensive peridural effusion was demonstrated by multiple roentgenographic techniques. Preliminary studies indicate that agents used in stellate block procedures also extend to the peridural space. These studies cast doubt on the specificity of sympathetic blockade techniques. The findings offer an explanation for some of the sensory and motor phenomena resulting from sympathetic blocks. Neurolytic drugs used in large volumes for sympathetic blocks cannot be assumed to always produce their effects by acting within the area of injection. Sympathetic block procedures are useful for diagnosis and treatment; however, the volume of injected agent used in sympathetic block procedures should be limited, and increased vigilance for complications which may result should be practiced.
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*Department of Anesthesiology, Albany Medical College of Union University and Albany Medical Center Hospital, Albany, New York. †Department of Anesthesiology, University of Miami School of Medicine, Miami, Florida, and the Winter Haven Hospital, Winter Haven, Florida. Presented at Southern Society of Anesthesiologists Meeting, New Orleans, Louisiana, March 26, 1966.
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Although single-shot caudal blockade is known as a relatively safe procedure, it is not always without complications.We present a case of accidental bladder puncture that was identified with fluoroscopy by chance after single-shot caudal blockade in a 17-months-old, 12 kg boy who underwent inguinal hernioplasty.(
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Lumbar, paravertebral sympathetic block injections with a lidocaine and contrast solution resulted in significant peridural spread of contrast solution. Bilateral, extensive peridural effusion was demonstrated by multiple roentgenographic techniques. Preliminary studies indicate that agents used in stellate block procedures also extend to the peridural space. These studies cast doubt on the specificity of sympathetic blockade techniques. The findings offer an explanation for some of the sensory and motor phenomena resulting from sympathetic blocks. Neurolytic drugs used in large volumes for sympathetic blocks cannot be assumed to always produce their effects by acting within the area of injection. Sympathetic block procedures are useful for diagnosis and treatment; however, the volume of injected agent used in sympathetic block procedures should be limited, and increased vigilance for complications which may result should be practiced.
Sympathetic nervous system
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