Anger expression and adaptation to childhood sexual abuse: The role of disclosure context

Previous research on anger and childhood sexual abuse (CSA) is largely cross-sectional and retrospective. In this study, we prospectively examined the consequences of expressing anger among sexually abused women in contexts of either voluntarily disclosing or not disclosing a previous abuse episode. All CSA survivors in the study had documented histories of CSA. These participants and a matched, nonabused sample were asked to describe their most distressing experience while being videotaped to allow coding of anger expression. Approximately two thirds of the CSA survivors voluntarily disclosed a previous abuse experience. Participants completed measures of internalizing symptoms and externalizing symptoms at the time of disclosure and again two years later. The expression of anger was associated with better long-term adjustment (decreased internalizing and externalizing symptoms) but only among CSA survivors who had expressed anger while not disclosing an abuse experience. For CSA survivors who disclosed an abuse experience, anger expression was unrelated to long-term outcome. These findings suggest that the benefits of anger expression for CSA survivors may be context specific

Trimeth­yl(triphenyl­meth­oxy)silane

In the title mol­ecule, C22H24OSi, the Si—O—C angle is 139.79 (11)°, the O—C—C angles of the triphenyl­meth­oxy group are in the range 106.13 (13)–109.22 (14)° and the O—Si—C angles of the trimethyl­sil­yloxy group are in the range 103.08 (10)–113.53 (10)°. In the crystal, face-to-face π–π interactions are observed between the phenyl rings [centroid separation = 4.194 (1) Å, interplanar spacing = 3.474 Å and centroid shift = 2.35 Å]. The three phenyl groups of the triphenyl­methyl substituent are mutually nearly perpendicular, with dihedral angles in the range 80.49 (8)–81.53 (8)°. There are only weak inter­molecular van der Waals inter­actions in the crystal

3-(4-Chloro­anilino)-5,5-dimethyl­cyclo­hex-2-en-1-one

The asymmetric unit of the title compound, C14H16ClNO, contains two independent mol­ecules, both with the cyclo­hexene ring in a sofa conformation. In the crystal, N—H⋯O hydrogen bonds link the mol­ecules related by translation along the a axis into two crystallographically independent chains. Weak C—H⋯π inter­actions are also observed

2-Methylxanthen-9-one

In the title compound, C14H10O2, the tricycle is not planar, being bent with a dihedral angle of 4.7 (1)° between the two benzene rings. In the crystal, π–π inter­actions between the six-membered rings of neighbouring mol­ecules [centroid–centroid distances = 3.580 (3) and 3.605 (3) Å] form stacks propagating along [101]

(E)-4-(4-Meth­oxy­phen­yl)but-3-en-2-one

In the title compound, C11H12O2, the dihedral angle between the benzene ring and the but-3-en-2-one group is 4.04 (5)°. The crystal packing features chains, parallel to [-101], composed of dimers connected by weak C—H⋯O inter­actions.

SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery.

Since the publication of the Society for Immunotherapy of Cancer\u27s (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients

Mocetinostat for patients with previously treated, locally advanced/metastatic urothelial carcinoma and inactivating alterations of acetyltransferase genes

BackgroundThe authors evaluated mocetinostat (a class I/IV histone deacetylase inhibitor) in patients with urothelial carcinoma harboring inactivating mutations or deletions in CREB binding protein [CREBBP] and/or E1A binding protein p300 [EP300] histone acetyltransferase genes in a singleâ arm, openâ label phase 2 study.MethodsEligible patients with platinumâ treated, advanced/metastatic disease received oral mocetinostat (at a dose of 70 mg 3 times per week [TIW] escalating to 90 mg TIW) in 28â day cycles in a 3â stage study (ClinicalTrials.gov identifier NCT02236195). The primary endpoint was the objective response rate.ResultsGenomic testing was feasible in 155 of 175 patients (89%). Qualifying tumor mutations were CREBBP (15%), EP300 (8%), and both CREBBP and EP300 (1%). A total of 17 patients were enrolled into stage 1 (the intentâ toâ treat population); no patients were enrolled in subsequent stages. One partial response was observed (11% [1 of 9 patients; the population that was evaluable for efficacy comprised 9 of the 15 planned patients]); activity was deemed insufficient to progress to stage 2 (null hypothesis: objective response rate of â ¤15%). All patients experienced â ¥1 adverse event, most commonly nausea (13 of 17 patients; 77%) and fatigue (12 of 17 patients; 71%). The median duration of treatment was 46 days; treatment interruptions (14 of 17 patients; 82%) and dose reductions (5 of 17 patients; 29%) were common. Mocetinostat exposure was lower than anticipated (doseâ normalized maximum serum concentration [Cmax] after TIW dosing of 0.2 ng/mL/mg).ConclusionsTo the authorsâ knowledge, the current study represents the first clinical trial using genomicâ based selection to identify patients with urothelial cancer who are likely to benefit from selective histone deacetylase inhibition. Mocetinostat was associated with significant toxicities that impacted drug exposure and may have contributed to modest clinical activity in these pretreated patients. The efficacy observed was considered insufficient to warrant further investigation of mocetinostat as a single agent in this setting.After the genomicâ based selection of patients with urothelial cancer with inactivating mutations/deletions in the histone acetyltransferase genes CREBBP and/or EP300, singleâ agent mocetinostat appears to be associated with significant toxicities that limit drug exposure. This may have contributed to the limited activity noted in the current phase 2 study (response rate of 11%) among heavily pretreated patients with platinumâ refractory disease.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147860/1/cncr31817_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147860/2/cncr31817.pd