Intraoperative Embolization during Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

Intraoperative tumor thrombus embolization is a potentially lethal complication during inferior vena cava (IVC) thrombectomy for renal cell carcinoma (RCC). Intraoperative embolization is uncommonly encountered because IVC thrombectomy surgical technique is focused on avoiding this complication. Nonetheless, early recognition of embolization is essential so that emergent management can be instituted.

Developing a post-treatment survivorship care plan to help breast cancer survivors understand their fertility.

Purpose: Reproductive-aged breast cancer survivors (BCS) who have completed initial cancer treatment frequently want to know about their future fertility potential. The purpose of this qualitative study was to assess if the fertility-related content presented in the survivorship care plan prototype met the informational needs of post-treatment BCS and to provide an opportunity for the target audience to review and react to the proposed content and design.

Methods: We conducted and analyzed transcripts from seven focus groups with BCS to evaluate their reactions to the survivorship care plan prototype.

The Value of Addressing Patient Preferences.

Recent scientific progress is, in some cases, leading to transformative new medicines for diseases that previously had marginal or even no treatment options. This offers great promise for people affected by these diseases, but it has also placed stress on the health care system in terms of the growing cost associated with some new interventions. Effort has been taken to create tools to help patients and health care providers assess the value of new medical innovations.

Adoption consideration and concerns among young adult female cancer survivors.

Purpose: We compared adoption consideration between female young adult cancer survivors and women of the same age in the general US population, hypothesizing that cancer survivors who desired children would report greater interest in adoption than an age-adjusted general population sample who desired children.

Methods: After age-standardizing the cancer survivor cohort to match the age distribution of the 2006-2010 National Survey for Family Growth (NSFG), we estimated adoption consideration among women age 18-35 years who wanted a (another) child in the two cohorts overall and within age groups. We assessed characteristics and concerns related to adoption consideration among cancer survivors.

Developing standards for breakthrough therapy designation in oncology.

In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential "breakthrough" drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a "Breakthrough Therapy", the U.

Use of multiple endpoints and approval paths depicts a decade of FDA oncology drug approvals.

This study explores the historic use of different endpoints to support regular and accelerated approval of cancer drugs between 2002 and 2012. In the past 10 years, two thirds of oncology regular approvals were based on endpoints other than overall survival. More than three quarters of accelerated approvals were based on response rates.

A fresh perspective on comparing the FDA and the CHMP/EMA: approval of antineoplastic tyrosine kinase inhibitors.

We compared and determined the reasons for any differences in the review and approval times of tyrosine kinase inhibitors (TKIs) by the US Food and Drug Administration (FDA) and the European EMA/CHMP. Applications for these novel cancer drugs were submitted to them within a mean of 31.2 days of each other, providing a fair basis for comparison.

Reducing the toxicity of cancer therapy: recognizing needs, taking action.

Our understanding of the biology of cancer and the application of this knowledge to cancer treatment has greatly outpaced what we know of the biology underlying the symptoms and toxic effects that therapies produce. These adverse effects of therapy cause substantial discomfort and distress to patients and their families, limit treatment tolerability and can persist indefinitely in post-treatment survivorship. Despite these concerns, little research effort is targeted at documenting the nature of these effects.

Despite criticism of the FDA review process, new cancer drugs reach patients sooner in the United States than in Europe.

The US Food and Drug Administration is often criticized as inefficient compared to its European counterpart, the European Medicines Agency. This criticism is especially common in the field of oncology, where severely ill patients have few therapeutic options. We conducted a direct drug-to-drug comparison of the two regulatory agencies' approvals of new oncology drugs.

TrxR, a new CovR-repressed response regulator that activates the Mga virulence regulon in group A Streptococcus.

Coordinate regulation of virulence factors by the group A streptococcus (GAS) Streptococcus pyogenes is important in this pathogen's ability to cause disease. To further elucidate the regulatory network in this human pathogen, the CovR-repressed two-component system (TCS) trxSR was chosen for further analysis based on its homology to a virulence-related TCS in Streptococcus pneumoniae. In a murine skin infection model, an insertion mutation in the response regulator gene, trxR, led to a significant reduction in lesion size, lesion severity, and lethality.

RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulon.

The CovR/S two-component system regulates the transcription of many genes that are crucial for the virulence of Streptococcus pyogenes (group A Streptococcus, GAS). Previously, we demonstrated that one gene repressed directly by CovR is rivR, which encodes a member of the RofA-like family of transcriptional regulators. In this study, we deleted rivR and its downstream gene rivX in a DeltacovR background.

Unraveling the regulatory network in Streptococcus pyogenes: the global response regulator CovR represses rivR directly.

The response regulator CovR acts as a master regulator of virulence in Streptococcus pyogenes by repressing transcription of approximately 15% of the group A streptococcus genome directly or indirectly. We demonstrate that phosphorylated CovR represses transcription of rivR directly by binding to conserved sequences located downstream from the promoter to block procession of RNA polymerase. This establishes the first link in a regulatory network where CovR interacts directly with other proteins that modulate gene expression.

Adoptive transfer of islet antigen-autoreactive T cell clones to transgenic NOD.Ea(d)mice induces diabetes indicating a lack of I-E mediated protection against activated effector T cells.

Transgenic insertion of the MHC class II Ea(d)gene in NOD mice restores I-E expression and prevents T-cell-mediated autoimmune diabetes (IDDM). The specific molecular and cellular mechanisms responsible for the diabetes resistance of transgenic NOD.Ea(d)mice remain unclear.