The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation.

Small ubiquitin-like modifier (SUMO) is a member of a ubiquitin-like protein superfamily. SUMOylation is a reversible posttranslational modification that has been implicated in the regulation of various cellular processes including inflammatory responses and expression of type 1 interferons (IFN1). In this report, we have explored the activity of the selective small molecule SUMOylation inhibitor subasumstat (TAK-981) in promoting antitumor innate immune responses.

A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models.

SUMOylation, the covalent conjugation of small ubiquitin-like modifier (SUMO) proteins to protein substrates, has been reported to suppress type I interferon (IFN1) responses. TAK-981, a selective small-molecule inhibitor of SUMOylation, pharmacologically reactivates IFN1 signaling and immune responses against cancers. In vivo treatment of wild-type mice with TAK-981 up-regulated IFN1 gene expression in blood cells and splenocytes.

Pan-TGFβ inhibition by SAR439459 relieves immunosuppression and improves antitumor efficacy of PD-1 blockade.

TGFβ is a pleiotropic cytokine that may have both tumor inhibiting and tumor promoting properties, depending on tissue and cellular context. Emerging data support a role for TGFβ in suppression of antitumor immunity. Here we show that SAR439459, a pan-TGFβ neutralizing antibody, inhibits all active isoforms of human and murine TGFβ, blocks TGFβ-mediated pSMAD signaling, and TGFβ-mediated suppression of T cells and NK cells.

Predicting neutropenia risk in patients with cancer using electronic data.

Objectives: Clinical guidelines recommending the use of myeloid growth factors are largely based on the prescribed chemotherapy regimen. The guidelines suggest that oncologists consider patient-specific characteristics when prescribing granulocyte-colony stimulating factor (G-CSF) prophylaxis; however, a mechanism to quantify individual patient risk is lacking. Readily available electronic health record (EHR) data can provide patient-specific information needed for individualized neutropenia risk estimation.

The Relationship Between Education and Prostate-Specific Antigen Testing Among Urban African American Medicare Beneficiaries.

Purpose: We examined the association between socioeconomic status (SES) and prostate-specific antigen (PSA) cancer screening among older African American men.

Methods: We analyzed baseline data from a sample of 485 community-dwelling African American men who participated in the Cancer Prevention and Treatment Demonstration Trial. The outcome was receipt of PSA screening within the past year.

Effect of Patient Navigation on Breast Cancer Screening Among African American Medicare Beneficiaries: A Randomized Controlled Trial.

Background: There is growing evidence that patient navigation improves breast cancer screening rates; however, there are limited efficacy studies of its effect among African American older adult women.

Objective: To evaluate the effect of patient navigation on screening mammography among African American female Medicare beneficiaries in Baltimore, MD.

Design: The Cancer Prevention and Treatment Demonstration (CPTD), a multi-site study, was a randomized controlled trial conducted from April 2006 through December 2010.

Extensive Deep Venous Thrombosis Resulting from Anterior Lumbar Spine Surgery in a Patient with Iliac Vein Compression Syndrome: A Case Report and Literature Review.

Study Design Case report. Objective Although May-Thurner syndrome or iliac vein compression syndrome is covered in the vascular literature, it remains absent from the orthopedic and neurosurgery literature and has not been previously reported to occur in concordance with spine surgery. We review the salient points of disease presentation, diagnosis, and treatment.

Effect of patient navigation on colorectal cancer screening in a community-based randomized controlled trial of urban African American adults.

Purpose: In recent years, colorectal cancer (CRC) screening rates have increased steadily in the USA, though racial and ethnic disparities persist. In a community-based randomized controlled trial, we investigated the effect of patient navigation on increasing CRC screening adherence among older African Americans.

Methods: Participants in the Cancer Prevention and Treatment Demonstration were randomized to either the control group, receiving only printed educational materials (PEM), or the intervention arm where they were assigned a patient navigator in addition to PEM.

Cyclin D activates the Rb tumor suppressor by mono-phosphorylation.

The widely accepted model of G1 cell cycle progression proposes that cyclin D:Cdk4/6 inactivates the Rb tumor suppressor during early G1 phase by progressive multi-phosphorylation, termed hypo-phosphorylation, to release E2F transcription factors. However, this model remains unproven biochemically and the biologically active form(s) of Rb remains unknown. In this study, we find that Rb is exclusively mono-phosphorylated in early G1 phase by cyclin D:Cdk4/6.

Multiple myeloma in the very old: an IASIA conference report.

Multiple myeloma (MM) in patients aged greater than 80 years poses an increasingly common challenge for oncology providers. A multidisciplinary workshop was held in which MM-focused hematologists/oncologists, geriatricians, and associated health-care team members discussed the state of research for MM therapy, as well as themes from geriatric medicine that pertain directly to this patient population. A summary statement of our discussions is presented here, in which we highlight several topics.

Calcium pyrophosphate dihydrate crystal deposition disease (pseudogout) of lumbar spine mimicking osteomyelitis-discitis with epidural phlegmon.

Calcium pyrophosphate dihydrate crystal deposition disease (pseudogout) of the axial spine is rare. To our knowledge, there are few reports of the disease presenting with a presumed diagnosis of infection in the lumbar spine. As reported here, the diagnosis of osteomyelitis-discitis with epidural phlegmon was presumed before intervention.

Gender differences in correlates of colorectal cancer screening among Black Medicare beneficiaries in Baltimore.

Background: Previous research has shown colorectal cancer (CRC) screening disparities by gender. Little research has focused primarily on gender differences among older Black individuals, and reasons for existing gender differences remain poorly understood.

Methods: We used baseline data from the Cancer Prevention and Treatment Demonstration Screening Trial.

High-grade adult isthmic L5-s1 spondylolisthesis: a report of intraoperative slip progression treated with surgical reduction and posterior instrumented fusion.

Adult isthmic spondylolisthesis most commonly occurs at the L5-S1 level of the lumbar spine. Slip progression is relatively rare in adults with this condition and slippage is typically associated with advanced degeneration of the disk below the pars defect. When symptomatic, radiculopathy is the typical complaint in adults with isthmic spondylolisthesis.

Activity of topotecan 21-day infusion in patients with previously treated large cell lymphoma: long-term follow-up of an Eastern Cooperative Oncology Group study (E5493).

The purpose of this study was to determine the activity of topotecan given by 21-day continuous infusion in patients previously treated with one prior therapy for a diffuse large-cell lymphoma or immunoblastic lymphoma. Patients with appropriate histology and measurable disease who had been treated with one prior chemotherapy regimen were eligible for study. Slides of tumor biopsies were submitted for central review of pathology.

Strong foreign promoters contribute to innate inflammatory responses induced by adenovirus transducing vectors.

E1-deleted adenovirus (FG Ad) transducing vectors are limited for use in vivo by their induction of strong innate and adaptive inflammatory responses. We have examined the contribution of the transgene cassette, particularly the foreign promoter driving transgene expression, in the induction of innate inflammation using a mouse ear model in which swelling is measured as a sensitive surrogate marker of the total innate inflammatory response. The commonly used cytomegalovirus major immediate early (CMV) promoter led to high-level swelling that was independent of transgene expression, while the Rous sarcoma virus and human ubiquitin C promoters led to intermediate levels of swelling and the Ad E1A promoter or no promoter led to equally low levels of swelling.

Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.

Introduction: Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC.

A randomized trial of a representational intervention to decrease cancer pain (RIDcancerPain).

Objective: Based on theories regarding cognitive representations of illness and processes of conceptual change, a representational intervention to decrease cancer pain (RIDcancerPain) was developed and its efficacy tested.

Design: A two-group RCT (RIDcancerPain versus control) with outcome and mediating variables assessed at baseline (T1) and 1 and 2 months later (T2 and T3). Subjects were 176 adults with pain related to metastatic cancer.

Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer.

Purpose: Perillyl alcohol (POH) is a naturally occurring lipid with preclinical activity against mammary carcinomas. We conducted a phase II multi-institutional study of oral POH administered four times daily in women with advanced treatment-refractory breast cancer.

Methods: Eligible women were treated with POH four times daily at 1,200-1,500 mg m(-2) dose(-1) on a 28-day cycle.

Recombinant adenoviral vectors can induce expression of p73 via the E4-orf6/7 protein.

Despite the utility of recombinant adenoviral vectors in basic research, their therapeutic promise remains unfulfilled. Most engineered adenoviral vectors use a heterologous promoter to transcribe a foreign gene. We show that adenoviruses containing the cytomegalovirus immediate-early promoter induce the expression of the proapoptotic cellular protein TAp73 via the cyclin-dependent kinase-retinoblastoma protein-E2F pathway in murine embryonic fibroblasts.

Multilevel spinal growth modulation with an anterolateral flexible tether in an immature bovine model.

Study Design: A bovine model was used to evaluate the effects of a multilevel anterolateral flexible tether in a growing spine.

Objective: To evaluate the radiographic changes in a growing spine with a multilevel anterolateral tether.

Summary Of Background Data: Spinal growth modulation has long been considered as a conceptually attractive and elegant possible alternative to arthrodesis in the treatment of idiopathic scoliosis.

Thoracic vertebral screw impingement on the aorta in an in vivo bovine model.

Study Design: A bovine model was used to evaluate the effects of thoracic vertebral screw impingement of the aorta.

Objectives: To evaluate the histologic and biomechanical changes in aortic wall tissue that was severely impinged by abutting instrumentation.

Summary Of Background Data: Case reports of vascular injury associated with spinal instrumentation generally describe intraoperative injury; some report delayed presentation of large vessel damage.