Human papillomavirus infection mediates response and outcome of vulvar squamous cell carcinomas treated with radiation therapy.

PURPOSE: Human papillomavirus (HPV) is implicated as a causative factor in vulvar squamous cell carcinoma (VSCC). This study evaluates if p16-positivity, a surrogate for HPV, predicts for better response rates to chemoradiation therapy and survival. MATERIALS AND METHODS: We conducted a retrospective chart review of women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000 to 2016 for VSCC. p16 stain-positivity was defined as diffuse strong "block" immunoreactivity within invasive tumor. RESULTS: Seventy-three women with median follow-up of 13.4 months were analyzed. Thirty-three (45.2%) had p16+ tumors. Median age was 73 years (range: 37-89); with p16+ tumors, the median age was 60 years vs 73 years for women with p16- tumors (p < 0.001). The distribution of tumor size and stage by p16-status were similar. The complete clinical response (cCR) rate for p16+ tumors was 63.6% vs 35.0% for p16- tumors (p = 0.014). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 53.8% vs 31.4% for p16+ vs p16-, respectively (p = 0.067). The combined complete response (cCR orpCR [CCR]) rate was 63.6% for p16+ and 30.0% for p16- (p = 0.004). Two-year vulvar control (VC) for women with p16+ tumors was 75.5% vs. 49.5% for p16- (p = 0.008). In women with p16+ tumors who achieved CCR, 2-year VC was 92.3% vs 52.1% for CIR (p = 0.009). For p16- tumors, 2-year VC was 67.3% vs 41.1% for CCR and CIR (p = 0.072). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p = 0.013). OS was not statistically different between p16+ cohorts, but was improved for p16- patients with CR vs CIR, 72.9% vs 18.8% (p = 0.026). CONCLUSIONS: p16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes.

Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.

Endoluminal management of bronchogenic carcinoma in 2010: diagnosis, staging, and therapy.

Endoluminal bronchogenic carcinoma, though a minority of lung cancer cases, presents a unique opportunity to utilize techniques for the diagnosis and therapy that are unavailable for more peripheral tumors. This review explores current techniques for the diagnosis, staging, and therapy of endoluminal central bronchogenic tumors and also introduces techniques currently under investigation as potential improvements or replacements for current techniques using recent literature. Additionally, the new staging criteria set forth in the 7th edition of the TMN staging system as a result of the American Joint Committee on Cancer (AJCC), International Union Against Cancer (IUCC), and the International Association for the Study of Lung Cancer (IASLC) are discussed with respect to endoluminal bronchogenic carcinoma.

Immunohistochemical evidence for an association of ribosomes with microfilaments in 3T3 fibroblasts.

Ribosome distribution in cultured fibroblasts was investigated immunohistochemically using antibodies which recognize the 60S ribosomal subunit. After treatment of cells with buffer containing 25mM KCl and 0.05% Nonidet-P40 immunostained material was present in punctate patterns and linear arrays consistent with some ribosomes being associated with the cytoskeleton. Treatment of the cells with 130mM KCl caused loss of both the beaded lines of immunostaining and micro-filaments. Double immunostaining showed ribosomes to be closely associated with microfilaments.

Increased association of ribosomes with myofibrils during the skeletal-muscle hypertrophy induced either by the beta-adrenoceptor agonist clenbuterol or by tenotomy.

Ribosome distribution in skeletal-muscle myofibres was investigated by immunohistochemistry and microdensitometry by using anti-(60 S ribosomal subunit) antibodies. Administration of the beta-adrenoceptor agonist clenbuterol caused an increase in the staining of the myofibrillar region with this antibody relative to that found in the subsarcolemmal cytoplasm. A similar effect was observed during hypertrophy of the plantaris muscle following severance of the tendon to the gastrocnemius. The results suggest that increased association of ribosomes with the myofibrils occurs during muscle hypertrophy.

Immunological localization of ribosomes in striated rat muscle. Evidence for myofibrillar association and ontological changes in the subsarcolemmal:myofibrillar distribution.

Ribosome distribution in skeletal-muscle fibres was investigated immunohistochemically by using polyclonal antibodies raised against large-ribosomal-subunit proteins isolated from rat liver. Immunoblot analysis showed the antibodies to recognize five major proteins of the large subunit; these were identified as L4, L6, L7, L15 and L17 by two-dimensional electrophoresis. Immunohistochemistry of frozen rat skeletal-muscle sections showed staining of both the subsarcolemmal and intermyofibrillar cytoplasm. A distinct banding pattern was observed, and when peroxidase and phase-contrast images of the same field were compared by image analysis the anti-ribosome staining was found to correspond to the A-bands. These results suggest that a proportion of muscle ribosomes are present in the myofibrillar cytoplasm in a regular fashion, possibly associated with myosin. Densitometric analysis of the peroxidase immunostaining showed that the ratio of myofibrillar to sub-sarcolemmal ribosomal material was lower in muscle from 51-day-old rats compared with those from 14-day-old animals.