Responsiveness of ovarian adenylyl cyclases to luteinizing hormone (LH), found to be 5 to 10-fold in cell-free preparations under optimal conditions, required gentle homogenizations and storage in sucrose-containing media. Assay conditions required the use of an ATP-regenerating system consisting of creatine kinase, creatine phosphate, and myokinase for the preservation of ATP levels. LH-stimulated adenylyl cyclase (AC) in rabbit CL showed the following properties: 1) The pH optimum of basal activity was about 8.0; that of LH-stimulated activity was about 7.5. 2) The relative response to LH was low (1.5 to 2-fold) at 0.1 mM ATP and increased with increasing ATP, but not with increasing GTP. At low (0.1 mM) ATP, GTP increased catalytic efficacy of the system, both in the absence and in the presence of LH (no effect on relative stimulation). 3) The optimal relative stimulation by LH was obtained at about 1.0 mM MgCl2 in excess of added magnesium-binding ingredients. 4) The sensitivity to stimulation by LH (about 0.2 mug/ml NIH-LH-B8) was unaffected by either pH, nucleotides (ATP and GTP), or MgCl2 concentration. 5) Under the assay conditions used, activity was stimulated by prostaglandin E1 (PGE1) about 1.5 to 2-fold, and by epinephrine about 3 to 4-fold. In all aspects tested, LH-stimulated AC in rat CL resembled that in rabbit CL, except that about 5-fold higher concentrations of NIH-LH-B8 were needed for half-maximal stimulation. The AC activity in pig Graafian follicles, however, differed from that in rabbit CL in that 1) the ATP concentration needed for optimal stimulation by LH was lower (in the micromolar rather than the millimolar range); 2) catecholamines elicited only a 1.3 to 1.4-fold stimulation; and 3) NIH-LH-B8 elicited half-maximal stimulation at 0.008 to 0.020 mug/ml. We were unable to detect LH-responsive AC activity in either homogenates or washed particles of CL from either cycling or pregnant pigs. LH fractions of three origins (human, bovine, and ovine) and of varying specific activities (from 0.041 to 2.0 NIH-LH-S18 units/mg) were tested and the relative potencies by OAAD assay were found to correlate well with the relative potencies in the adenylyl cyclase assays (rat CL, rabbit CL, and pig follicles), consistent with the possibility that AC receptors are responsible for biologic actions of LH.

Background Reference centers (RCs) are a key point for improving the survival of patients with soft‐tissue sarcomas (STS). The aim of this study was to evaluate selected items in the management of patients with STS, comparing results between RC and local hospitals (LHs). Materials and Methods Diagnostic and therapeutic data from patients diagnosed between January 2004 and December 2011 were collected. Correlation with outcome was performed. Results A total of 622 sarcomas were analyzed, with a median follow‐up of 40 months. Imaging of primary tumor preoperatively (yes vs. no) correlated with a higher probability of free surgical margins (77.4% versus 53.7%; p = .006). The provenance of the biopsy (RC vs. LH) significantly affected relapse‐free survival (RFS; 3‐year RFS 66% vs. 46%, respectively; p = .019). Likewise, 3‐year RFS was significantly worse in cases with infiltrated (55.6%) or unknown (43.4%) microscopic surgical margins compared with free margins (63.6%; p < .001). Patients managed by RCs had a better 3‐year overall survival compared with those managed by LHs (82% vs. 70.4%, respectively; p = .003). Perioperative chemotherapy in high‐risk STS, more frequently administered in RCs than in LHs, resulted in significantly better 3‐year RFS (66% vs. 44%; p = .011). In addition, patients with stage IV disease treated in RCs survived significantly longer compared with those in LHs (30.4 months vs. 18.5 months; p = .036). Conclusion Our series indicate that selected quality‐of‐care items were accomplished better by RCs over LHs, all with significant prognostic value in patients with STS. Early referral to an RC should be mandatory if the aim is to improve the survival of patients with STS. Implications for Practice This prospective study in patients diagnosed with soft‐tissue sarcoma shows the prognostic impact of reference centers in the management of these patients. The magnitude of this impact encompasses all steps of the process, from the initial management (performing diagnostic biopsy) to the advanced disease setting. This is the first prospective evidence showing improvement in outcomes of patients with metastatic disease when they are managed in centers with expertise. This study provides extra data supporting referral of patients with sarcoma to reference centers.

Background: Pericardial synovial sarcomas (PSS) are very rare tumors, with dismal prognosis and limited data. We describe the clinical features and identify prognostic factors of primary PSS. Case Report: We describe the case of a 56-year-old male patient with PSS managed by the multidisciplinary team of thoracic oncology. The therapeutic plan comprised surgery, chemotherapy, stereotactic radiosurgery and targeted therapy, with excellent results. Materials and Methods: Data from 37 cases reported in English during the past 20 years were gathered and analyzed. PSS was found to occur at a mean age of 36±17.082 (range=13-67) years. Survival analysis was performed on 20 cases with follow-up of at least 6 months. Conclusion: Only complete resection of the tumor seems to be an independent prognostic factor. To our knowledge, this is the first report on the safety and effectivity of pazopanib in PSS and may provide guidance for similar cases in the future.

Soft tissue sarcomas (STS) are rare tumors; they do not even equate to 1% of all malignant tumor cases. One-fifth of all STS occur in the upper extremities, where epithelioid sarcoma, synovial sarcoma, clear cell sarcoma and malignant fibrohistiocytoma are the most frequent subtypes. Surgical resection is the cornerstone of treatment. However, accomplishment of optimal oncological and functional results of STS of the upper extremities may represent a challenge for hand surgeons, due to the complex anatomy. In several cases, preoperative therapies are needed to facilitate tumor resection and improve the oncological outcome. Oligometastatic disease may also be a challenging scenario as curative strategies can be applied. Radiotherapy and chemotherapy are commonly used for this purpose albeit with conflicting evidence. Novel drug combinations have also been approved in the metastatic setting, further improving the quality of life and survival of eligible patients. Thus, prior to any approach, every case should be individually discussed in sarcoma centers with specialized multidisciplinary tumor boards. The aim of the present review was to gather the multidisciplinary experiences of the available therapeutic strategies for STS of the upper extremities.

Despite significant advances in multidisciplinary treatment strategies including surgery, radiotherapy, targeted therapy and chemotherapy there are yet no substantial improvements in the clinical benefit of patients with sarcomas. Current understanding of the underlying cellular and molecular pathways which govern the dynamic interactions between the tumor stroma, tumor cells and immune infiltrates in sarcoma tissues, led to the clinical development of new therapeutic options based on immunotherapies. Moreover, progress of the treatment of sarcomas also depends on the identification of biomarkers with prognostic and predictive values for selecting patients most likely to benefit from these new therapeutic treatments and also serving as potent therapeutic targets. Novel combinations with radiotherapy, chemotherapy, targeted therapy, vaccines, CAR-T cells and treatments targeting other immune components of the tumor microenvironment are underway aiming to bypass known resistance mechanisms. This review focuses on the role of tumor microenvironment in sarcoma, prognosis and response to novel immunotherapies.