Increased cell size, structural complexity and migration of cancer cells acquiring fibroblast organelles by cell-projection pumping.

We recently described a hydrodynamic mechanism for cytoplasmic transfer between cells, termed cell-projection pumping (CPP). Earlier image analysis related altered SAOS-2 osteosarcoma cell morphology, to what we now recognize as CPP uptake of fibroblast cytoplasm. We here examine SAOS-2 phenotype following co-culture with human dermal fibroblasts (HDF) in which organelles were pre-labelled with a fluorescent lipophilic marker.

Plate-assisted Bone Segment Transport With Motorized Lengthening Nails and Locking Plates: A Technique to Treat Femoral and Tibial Bone Defects.

Unlabelled: This article describes a new bone transport technique for femoral and tibial bone defects using lengthening nails combined with locking plates. We term it plate-assisted bone segment transport (PABST).

Methods: Nine patients with five femoral and four tibial bone defects from open fractures or malignancies were treated between 2016 and 2018.

Integrative Medicine Therapies for Pain Management in Cancer Patients.

Pain management for cancer patients should include pharmacologic and nonpharmacologic interventions. Integrative medicine therapies, such as mind-body practice, acupuncture, massage therapy, and music therapy, have been studied for their roles in pain management. Data from randomized controlled trials support the effect of hypnosis, acupuncture, and music therapy in reduction of pain.

Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.

Background: Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.

Methods: We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo.

Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.

Background: In an early-phase study involving patients with advanced non-small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab monotherapy, particularly among patients with tumors that expressed programmed death ligand 1 (PD-L1). Data are needed to assess the long-term benefit of nivolumab plus ipilimumab in patients with NSCLC.

Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IV or recurrent NSCLC and a PD-L1 expression level of 1% or more in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy.

Impact of Unilateral versus Bilateral Breast Reconstruction on Procedure Choices and Outcomes.

Background: In choosing between implant-based and autologous breast reconstruction, surgeons and patients must weigh relative risks and benefits. However, differences in outcomes across procedure types may vary between unilateral versus bilateral reconstructions. Procedure-related differences in complications and patient-reported outcomes were evaluated for unilateral and bilateral reconstruction.

Preventing Treatment-Related Functional Decline: Strategies to Maximize Resilience.

The majority of patients with cancer are older adults. A comprehensive geriatric assessment (CGA) will help the clinical team identify underlying medical and functional status issues that can affect cancer treatment delivery, cancer prognosis, and treatment tolerability. The CGA, as well as more abbreviated assessments and geriatric screening tools, can aid in the treatment decision-making process through improved individualized prediction of mortality, toxicity of cancer therapy, and postoperative complications and can also help clinicians develop an integrated care plan for the older adult with cancer.

Addressing the Unintentional Consequences of Cancer Therapy With Novel Integrative Therapeutics.

There are 15.5 million cancer survivors in the United States because of, in part, improvements in therapy. As a result, there will be an increased burden of long- and late-term complications of cancer care, such as metabolic alterations.

Relationships Among DNP and PhD Students After Implementing a Doctoral Student Organization.

Background: Early career contact, between clinically focused DNP and research-focused PhD nursing students, may encourage desirable intradisciplinary synergies.

Aim: The aim of the study was to assess relationships among DNP and PhD nursing students after initiating a doctoral student organization.

Method: An online survey assessed student interaction pre- and post-doctoral student organization implementation.

Malignant Pleural Mesothelioma: Are There Imaging Characteristics Associated With Different Histologic Subtypes on Computed Tomography?

Objectives: Determine imaging characteristics specific to epithelioid (eMPM), sarcomatoid (sMPM), and biphasic (bMPM) subtypes of malignant pleural mesothelioma (MPM) on computed tomography.

Methods: Preoperative computed tomography scans of patients with MPM were retrospectively assessed for numerous features including primary affected side, volume loss, pleural thickness, pleural calcifications, pleural effusion, and lymphadenopathy.

Results: One hundred twenty-five patients with MPM were included.

Selective Nanoparticle Targeting of the Renal Tubules.

Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs.

Breast Reconstruction and Radiation Therapy: An Update.

With the indications for radiation therapy in the treatment of breast cancer continuing to expand, many patients present for reconstruction having previously had radiation or having a high likelihood of requiring radiation following mastectomy. Both situations are challenging for the plastic surgeon, with different variables impacting the surgical outcome. To date, multiple studies have been performed examining prosthetic and autologous reconstruction in this setting.

Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma.

Background: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial.

Methods: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent.

snoRNAs contribute to myeloid leukaemogenesis.

The mechanism of action of oncogenes in acute myeloid leukaemia is poorly understood. A study now shows that the fusion oncoprotein AML1-ETO regulates leukaemogenesis by increasing the expression of small nucleolar RNAs through post-transcriptional mechanisms, resulting in increased ribosomal RNA methylation, protein translation, and promotion of leukaemic-cell self-renewal and growth.

Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.

Background: Olaparib is an oral poly(adenosine diphosphate-ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation.

Methods: We conducted a randomized, open-label, phase 3 trial in which olaparib monotherapy was compared with standard therapy in patients with a germline BRCA mutation and human epidermal growth factor receptor type 2 (HER2)-negative metastatic breast cancer who had received no more than two previous chemotherapy regimens for metastatic disease. Patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or standard therapy with single-agent chemotherapy of the physician's choice (capecitabine, eribulin, or vinorelbine in 21-day cycles).

Bench-to-Bedside Approaches for Personalized Exercise Therapy in Cancer.

The past 2 decades have witnessed a growing body of work investigating the feasibility and efficacy of exercise therapy on a broad array of outcomes in many different oncology scenarios. Despite this heterogeneity, the exercise therapy prescription approach and the dose tested has been largely similar. Thus, current exercise therapy prescriptions in the oncology setting adopt a one-size-fits-all approach.

Kaposi sarcoma, oral malformations, mitral dysplasia, and scoliosis associated with 7q34-q36.3 heterozygous terminal deletion.

Chromosome 7 germline macrodeletions have been implicated in human congenital malformations and developmental delays. We herein report a novel heterozygous macrodeletion of 7q34-q36.3 in a 16-year-old girl originally from West Indies.

HMG-CoA synthase 1 is a synthetic lethal partner of BRAF in human cancers.

Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using an RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF up-regulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAF-dependent MEK1 activation in human cancer.

RNF11 sequestration of the E3 ligase SMURF2 on membranes antagonizes SMAD7 down-regulation of transforming growth factor β signaling.

The activity of the E3 ligase, SMURF2, is antagonized by an intramolecular, autoinhibitory interaction between its C2 and Hect domains. Relief of SMURF2 autoinhibition is induced by TGFβ and is mediated by the inhibitory SMAD, SMAD7. In a proteomic screen for endomembrane interactants of the RING-domain E3 ligase, RNF11, we identified SMURF2, among a cohort of Hect E3 ligases previously implicated in TGFβ signaling.

Participation in Activities Associated With Quality of Life for Long-Term Survivors of Rectal Cancer.

Context: Cancer patients' participation in social, recreational, and civic activities is strongly associated with quality of life (QOL), but these activities are not well integrated into cancer survivorship research or interventions.

Objective: Test the hypothesis that for long-term (≥ 5 years) survivors of rectal cancer, clinical factors (type of surgery and bowel function) are associated with long-term participation in activities and that participation in activities is associated with long-term QOL.

Design: Observational study with longitudinal and cross-sectional components.

Update on Ophthalmic Oncology 2014: Retinoblastoma and Uveal Melanoma.

Purpose: The aim of this study was to review peer-reviewed articles on ophthalmic oncology (specifically retinoblastoma and uveal melanoma) published from January to December 2014.

Design: This study is a literature review.

Methods: The terms retinoblastoma and uveal melanoma were used in a MEDLINE literature search.