Ocean acidification disrupts the orientation of postlarval Caribbean spiny lobsters

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Gravinese, P. M., Page, H. N., Butler, C. B., Spadaro, A. J., Hewett, C., Considine, M., Lankes, D., & Fisher, S. Ocean acidification disrupts the orientation of postlarval Caribbean spiny lobsters. Scientific Reports, 10(1), (2020): 18092, doi:10.1038/s41598-020-75021-9.Anthropogenic inputs into coastal ecosystems are causing more frequent environmental fluctuations and reducing seawater pH. One such ecosystem is Florida Bay, an important nursery for the Caribbean spiny lobster, Panulirus argus. Although adult crustaceans are often resilient to reduced seawater pH, earlier ontogenetic stages can be physiologically limited in their tolerance to ocean acidification on shorter time scales. We used a Y-maze chamber to test whether reduced-pH seawater altered the orientation of spiny lobster pueruli toward chemical cues produced by Laurencia spp. macroalgae, a known settlement cue for the species. We tested the hypothesis that pueruli conditioned in reduced-pH seawater would be less responsive to Laurencia spp. chemical cues than pueruli in ambient-pH seawater by comparing the proportion of individuals that moved to the cue side of the chamber with the proportion that moved to the side with no cue. We also recorded the amount of time (sec) before a response was observed. Pueruli conditioned in reduced-pH seawater were less responsive and failed to select the Laurencia cue. Our results suggest that episodic acidification of coastal waters might limit the ability of pueruli to locate settlement habitats, increasing postsettlement mortality.We thank the Steinwachs Family Foundation, which provided funding that supported Gravinese’s postdoctoral fellowship at Mote Marine Laboratory and Aquarium. We also acknowledge the partial support provided by the St. Petersburg College Titan Achievement minigrant program. Page was supported by a Mote Marine Laboratory and Aquarium Postdoctoral Research Fellowship. Postlarval spiny lobsters were collected with a state-issued Special Activity License (SAL-17-1868G-SR). We also thank those who helped with animal collection throughout this work including in-kind support provided by E. Muller and the Mote CAOS facility, as well as E. Bartels and C. Walter of the Coral Reef Monitoring and Assessment Program at Mote Marine Laboratory and Aquarium, as well as other field personnel including: L. Toth, S. Perry, T. Parker, A. Fine, L. Humphrey, and many undergraduate interns. We also thank L. Toth, E. Ross, B. Sharp, C. Crowley, J. Butler, and B. Crowder for editorial comments

Toward improving practices for submission of diagnostic tissue blocks for National Cancer Institute clinical trials

OBJECTIVES: The National Cancer Institute (NCI) National Clinical Trials Network performs phase II and III clinical trials, which increasingly rely on the submission of diagnostic formalin-fixed, paraffin-embedded tissue blocks for biomarker assessment. Simultaneously, advances in precision oncology require that clinical centers maintain diagnostic specimens for ancillary, standard-of-care diagnostics. This has caused tissue blocks to become a limited resource for advancing the NCI clinical trial enterprise and the practice of modern molecular pathology. METHODS: The NCI convened a 1-day workshop of multidisciplined experts to discuss barriers and strategic solutions to facilitate diagnostic block submission for clinical trial science, from the perspective of patient advocates, legal experts, pathologists, and clinical oncologists. RESULTS: The expert views and opinions were carefully noted and reported. CONCLUSIONS: Recommendations were proposed to reduce institutional barriers and to assist organizations in developing clear policies regarding diagnostic block submission for clinical trials

Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. RESULTS: Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. CONCLUSION: Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC

A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study

PURPOSE: Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer. PATIENTS AND METHODS: Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]). RESULTS: Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD. CONCLUSION: Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity

Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study

This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC

Circulating Tumor Cells In Advanced Cervical Cancer: NRG Oncology-Gynecologic Oncology Group Study 240 (NCT 00803062)

To isolate circulating tumor cells (CTCs) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival (OS) and progression-free survival (PFS). 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the anti-angiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin positive/anti-CD45 negative cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semi-automated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0–18) and, at 36 days post-treatment, was 4 (range, 0–17). The greater the declination in CTCs between time points studied, the lower the risk of death (HR 0.87; 95% CI, 0.79–0.95). Among patients with high (≥ median) pre-treatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR 0.57; 95% CI, 0.32–1.03) and progression (PFS HR 0.59; 95% CI, 0.36–0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pre-treatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker

on the surface

simple method for displaying recalcitrant protein

Anti-PD-L1 (atezolizumab) as an immune primer and concurrently with extended-field chemoradiotherapy for node-positive locally advanced cervical cancer

BackgroundThere is a lack of data exploring the use and optimal timing of immunotherapy and chemoradiation therapy (CRT) in node-positive cervical cancer. Further translational research into mechanisms of response and resistance to immunotherapy in advanced cervical cancer is warranted.Primary objectivesTo determine if sequencing of atezolizumab and CRT result in differential immune activation, as determined by clonal expansion of T cell receptor beta (TCRB) repertoires in peripheral blood on day 21.Study hypothesisThere is a difference for clonal expansion of T cell receptor beta repertoires in the peripheral blood at day 21 between the priming and concurrent atezolizumab and CRT in Arm A vs the concurrent atezolizumab and CRT in Arm B.Trial designLocally advanced cervical cancer patients with lymph node-positive disease will be randomized on this open-label, randomized trial with two experimental arms. Arm A will get one dose of atezolizumab prior to cisplatin CRT, and then two subsequent doses of atezolizumab during the CRT, and Arm B will get three doses during CRT. Patients will be followed for 2 years to assess outcomes.Major inclusion/exclusion criteriaPatients must have histologically confirmed, newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): FIGO 2009 clinical stages IB2/IIA with positive para-aortic nodes, or FIGO 2009 clinical stages IIB/IIIB/IVA with positive pelvic or para-aortic lymph nodes. Exclusion criteria include those who had a prior hysterectomy or lymph node dissection.Primary endpointsClonal expansion of TCRB) repertoires in peripheral blood on day 21.Sample sizeThe sample size will be 40 patients.Estimated dates for completing accrual and presenting resultsWe estimate accrual to finish by the summer of 2020 with presentation of results to follow in 2021.Trial registrationNCT03738228

TP011/#1527 GOG 3039 a phase II study of abemaciclib in combination with letrozole in advanced, recurrent or metastatic endometrioid endometrial cancer

ObjectivesPrimary Objective: To evaluate the efficacy in terms of the probability of surviving progression free for at least 6 months (PFS at 6 mo). Secondary Objective: To determine the proportion responding by RECIST v1.1 in patients with advanced, persistent, or recurrent endometrioid endometrial cancer. To estimate the time to disease progression or death (PFS and OS endpoints). To describe the toxicities in patients receiving combination therapy with letrozole and abemaciclib with advanced/metastatic endometrial cancer.MethodsKey Eligibility Criteria:-Advanced (FIGO 2014 Stage III or IV), persistent, or recurrent endometrial carcinoma -Must have endometrioid histology (all grades allowed) (Hormone receptor status is not required for enrollment). -Must have measurable disease by RECIST v1.1. -Prior chemotherapy in the adjuvant setting for Stage I, II, or III is permitted. -Prior chemoradiotherapy for a pelvic recurrence is permitted. -Prior immunotherapy and/or targeted therapy is allowed in addition to, in combination with, in lieu of, or subsequent to prior chemotherapy. Regardless of circumstances, no more than one prior chemotherapy regimen (including chemo-radiotherapy) is permitted, and no more than one additional systemic therapy is permitted. Hence, eligible patient may have received 0, 1, or 2 prior lines of systemic therapy and for women who received two prior lines of therapy, only one of them may have included chemotherapy. -ECOG performance status of 0–1. -Must be able to swallow oral medications.ResultsTrial in progress: there are no available results at the time of submission.ConclusionsTrial in progress: there are no available conclusions at the time of submission