Serial transperineal sector prostate biopsies: impact on long-term erectile dysfunction

James JY Chong, Mieke Van Hemelrijck, Declan Cahill and Janette Kinsella

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Cancers, Vol. 8, Pages 52: The MYC 3′ Wnt-Responsive Element Drives Oncogenic MYC Expression in Human Colorectal Cancer Cells

Mutations in components of the Wnt/β-catenin signaling pathway drive colorectal cancer (CRC) by deregulating expression of downstream target genes including the c-MYC proto-oncogene (MYC). The critical regulatory DNA enhancer elements that control oncogenic MYC expression in CRC have yet to be fully elucidated. In previous reports, we correlated T-cell factor (TCF) and β-catenin binding to the MYC 3′ Wnt responsive DNA element (MYC 3′ WRE) with MYC expression in HCT116 cells. Here we used CRISPR/Cas9 to determine whether this element is a critical driver of MYC. We isolated a clonal population of cells that contained a deletion of a single TCF binding element (TBE) within the MYC 3′ WRE. This deletion reduced TCF/β-catenin binding to this regulatory element and decreased MYC expression. Using RNA-Seq analysis, we found altered expression of genes that regulate metabolic processes, many of which are known MYC target genes. We found that 3′ WRE-Mut cells displayed a reduced proliferative capacity, diminished clonogenic growth, and a decreased potential to form tumors in vivo. These findings indicate that the MYC 3′ WRE is a critical driver of oncogenic MYC expression and suggest that this element may serve as a therapeutic target for CRC.

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Issue Information

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MANAGEMENT OF HEMOPOIETIC NEOPLASIAS DURING PREGNANCY

Publication date: Available online 22 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Semra Paydas
Hemopoietic neoplasias are unique cancers generally affecting bone marrow, and requires a special attention for disease control and also their complications. When these neoplastic disorders accompany to pregnancy there are are many risks both for mother and foetus. Diagnostic difficulties due to the limited use of imaging modalities is essential in pregnant women. On the other hand suboptimal using of the anti-neoplastic drugs and their higher toxicity in mother and foetus must be considered in the management of these neoplastic disorders. Due to the lack of therapeutic guidelines in these cases, team approach is essential and therapy requires to the use the art of medicine.



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Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma: An updated review of published data from the named patient program

Publication date: Available online 21 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): P.L. Zinzani, S. Sasse, J. Radford, A. Gautam, V. Bonthapally
Brentuximab vedotin was available via Named Patient Program (NPP) to patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) or systemic anaplastic large-cell lymphoma in ∼60 non-US/Canadian countries, before local approval. Published results were examined recently; through systematic literature review, we identified 12 new NPP publications. Most (10/12) publications included new NPP data describing 8 unique cohorts (N=480; all R/R HL) and new participating countries. Overall response rates were 58–80%, and complete remission rates were 10–40%. With median follow-up of 9.5–26 months, median progression-free survival was 5–10.5 months and median overall survival (OS) had not been reached in most cohorts; 1- and 2-year OS was 67–76% and 58–67%, respectively. Tolerability was as expected from previous reports. Despite intrinsic bias and heterogeneous cohorts, this update supports previous findings showing comparable efficacy and tolerability of brentuximab vedotin between real-world practice and phase 2 trial results in R/R HL.



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4-1BB aptamer based immunomodulation enhances the therapeutic index of radiotherapy in murine tumor models

Publication date: Available online 21 May 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Ana Paula Benaduce, Randall Brenneman, Brett Schrand, Alan Pollack, Eli Gilboa, Adrian Ishkanian
PurposeThere is growing evidence to suggest checkpoint blockade immunotherapy such as Ipilimumab and Nivolumab can significantly improve radiation induced solid tumor control. Preclinical data suggests that combining co-stimulatory agents with checkpoint blockade and radiation will significantly improve responses. However, clinical translation of co-stimulatory antibodies, such as 4-1BB, have been hindered by dose limiting toxicity. We report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for co-stimulation, and show combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies.Methods & MaterialsSubcutaneous 4T1 (mouse mammary carcinoma) tumors were established (∼100 mm³) and an RT dose/fractionation schedule that optimally synergizes with 4-1BB mAb was identified. Comparable tumor control and animal survival was observed when either 4-1BB antibody or aptamer were combined with RT using models of breast cancer and melanoma (4T1 and B16-F10). Off-target CD8+ T cell toxicity was evaluated by quantification of CD8+ T cells in livers and spleens of treated animals.ResultsWhen combined with 4-1BB mAb, significant differences in tumor control were observed by varying RT dose and fractionation schedules. Optimal synergy between RT and 4-1BB mAb was observed at 5Gyx6. Testing 4-1BB mAb and aptamer independently using the optimal RT (5Gyx6 for 4T1/Balb/c and 12Gyx1 for B16/C57BL6J mouse models), revealed equivalent tumor control using 4-1BB aptamer and 4-1BB mAb. 4-1BB mAb, but not 4-1BB aptamer-treated animals exhibited increased lymphocytic liver infiltrates and increased splenic and liver CD8⁺ T cells.ConclusionsRT synergizes with 4-1BB mAb and this effect is dependent on RT dose and fractionation. Tumor control by 4-1BB aptamer is equivalent to 4-1BB mAb when combined with optimal RT dose, without eliciting off-target liver and spleen CD8+ expansion. 4-1BB aptamer –based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control.

Teaser

Off-target toxicity of co-stimulatory mAbs such as 4-1BB hinders their clinical translation. Combining RT with 4-1BB aptamer or 4-1BB mAb therapy exhibited equivalent tumor control in murine tumor models. 4-1BB aptamer treatment did not promote CD8+ T cell liver and spleen infiltration, suggesting a superior therapeutic index over mAb. This study provides preliminary rationale for development of costimulatory aptamers as a complementary strategy for combination with RT and existing checkpoint blockade mAbs.


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[Evaluation of the impact of breast reconstruction in women in couple through a community-based research tool: The Seintinelles].

[Evaluation of the impact of breast reconstruction in women in couple through a community-based research tool: The Seintinelles].

Bull Cancer. 2016 May 17;

Authors: Lamore K, Quintard B, Flahault C, Van Wersch A, Untas A

Abstract
This preliminary study explores the psychological and marital impact of breast reconstruction (or lack thereof) in women who had a mastectomy due to breast cancer. The study was carried out through an innovative and French community-based research tool on cancer: the Seintinelles. Sixty-nine partnered women treated for breast cancer participated, divided into 3 groups: 19 without breast reconstruction, 24 with immediate breast reconstruction and 26 with delayed breast reconstruction. They completed online questionnaires measuring both satisfaction and regret about the decision related to breast reconstruction, quality of life after breast surgery (EORTC-BRR), emotional state (POMS) and marital intimacy (PAIR). Recruitment through the Seintinelles had the advantage of being quick and national, but the profile of participants deviated from the mean population in the sense that our subjects were on average younger than women affected by breast cancer and had faced more breast cancer in their family. The results revealed that women are satisfied with their choice (little regret), have a similar emotional experience and good marital intimacy. However, women without breast reconstruction would less recommend their decision to others and were less satisfied with the aesthetic result, compared to women with breast reconstruction. These results highlight that psychological and marital impact seems comparable in women with and without reconstruction. Future studies are needed to better understand the role of the partner in the recourse of breast reconstruction.

PMID: 27206823 [PubMed - as supplied by publisher]

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