Axillary sentinel lymph node biopsy after mastectomy: a case report

<p>Abstract</p> <p>Background</p> <p>Sentinel lymph node biopsy has been established as the preferred method for staging early breast cancer. A prior history of mastectomy is felt to be a contraindication.</p> <p>Case presentation</p> <p>A patient with recurrent breast cancer in her skin flap was discovered to have positive axillary sentinel nodes by sentinel lymph node biopsy five years after mastectomy for ductal carcinoma in situ.</p> <p>Conclusion</p> <p>A prior history of mastectomy may not be an absolute contraindication to sentinel lymph node biopsy.</p

Workshop Report for Cancer Research: Defining the Shades of Gy: Utilizing the Biological Consequences of Radiotherapy in the Development of New Treatment Approaches—Meeting Viewpoint

The ability to physically target radiotherapy using image-guidance is continually improving with photons and particle therapy that include protons and heavier ions such as carbon. The unit of dose deposited is the gray (Gy); however, particle therapies produce different patterns of ionizations, and there is evidence that the biological effects of radiation depend on dose size, schedule, and type of radiation. This National Cancer Institute (NCI)–sponsored workshop addressed the potential of using radiation-induced biological perturbations in addition to physical dose, Gy, as a transformational approach to quantifying radiation

Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model

Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in <i>Sirt2</i> wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from <i>Sirt2</i> WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington’s, Parkinson’s, and Alzheimer’s were acutely affected by radiation within 72 h of treatment. Although loss of <i>Sirt2</i> preferentially affected both Huntington’s and Parkinson’s pathways, WBRT most significantly affected Huntington’s-related proteins in the absence of <i>Sirt2</i>. Identical protein expression patterns were identified in Mog following WBRT in both <i>Sirt2</i> WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of <i>Sirt2</i> can have significant effects on the brain proteome and its response to ionizing radiation

Radiation-Induced Alteration of the Brain Proteome: Understanding the Role of the Sirtuin 2 Deacetylase in a Murine Model

Whole brain radiotherapy (WBRT) produces unwanted sequelae, albeit via unknown mechanisms. A deacetylase expressed in the central nervous system, Sirtuin 2 (SIRT2), has been linked to neurodegeneration. Therefore, we sought to challenge the notion that a single disease pathway is responsible for radiation-induced brain injury in <i>Sirt2</i> wild-type (WT) and knockout (KO) mice at the proteomic level. We utilized isobaric tag for relative and absolute quantitation to analyze brain homogenates from <i>Sirt2</i> WT and KO mice with and without WBRT. Selected proteins were independently verified, followed by ingenuity pathway analysis. Canonical pathways for Huntington’s, Parkinson’s, and Alzheimer’s were acutely affected by radiation within 72 h of treatment. Although loss of <i>Sirt2</i> preferentially affected both Huntington’s and Parkinson’s pathways, WBRT most significantly affected Huntington’s-related proteins in the absence of <i>Sirt2</i>. Identical protein expression patterns were identified in Mog following WBRT in both <i>Sirt2</i> WT and KO mice, revealing a proteomic radiation signature; however, long-term radiation effects were found to be associated with altered levels of a small number of key neurodegeneration-related proteins, identified as Mapt, Mog, Snap25, and Dnm1. Together, these data demonstrate the principle that the presence of <i>Sirt2</i> can have significant effects on the brain proteome and its response to ionizing radiation

Pilot trial of topical MTS-01 application to reduce dermatitis in patients receiving chemoradiotherapy for stage I–III carcinoma of the anal canal

The purpose of the present trial was to determine the feasibility of the daily topical application of the piperidine nitroxide, MTS‑01, combined with chemoradiotherapy in the treatment of patients with anal carcinoma. The secondary study endpoints were the description of the effects of this agent on skin toxicity and rectal‑associated lymphoid tissue. The participants received radiotherapy concurrent with mitomycin‑C and 5‑fluorouracil for carcinoma of the anal canal. MTS‑01 was applied to the bilateral inguinal area and the gluteal cleft. Dermatologic and non‑dermatologic toxicity was graded throughout the treatment period. Circulating lymphocytes were serially collected for phenotyping. Rectal mucosal snag biopsies were collected at baseline and at&nbsp;1&nbsp;year of follow‑up. A total of 5&nbsp;patients received topical MTS‑01. Adverse events attributed to MTS‑01 included asymptomatic grade&nbsp;1 hypoglycemia and grade&nbsp;1‑2 diarrhea. Dermatitis within untreated, radiated skin was not more severe than dermatitis in MTS‑01‑treated, unirradiated skin. Circulating CD4+ lymphocyte suppression was noted at&nbsp;&gt;1&nbsp;year following treatment in human immunodeficiency virus‑negative participants. CD4+ lymphocytes remained suppressed in the irradiated rectal mucosa at&nbsp;1&nbsp;year, whereas the CD8+ lymphocyte numbers recovered or increased. On the whole, the present study demonstrates that the MTS‑01 topical application was tolerable with minimal toxicity. Chemoradiation for anal cancer led to prolonged CD4+ lymphocytopenia in the circulation and gut mucosa

Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach

AbstractWe tested the hypothesis that the effects on gene expression of altered DNA methylation by 5-aza-2′-deoxycytidine (5-aza-CdR) and genetic (DNMT knockout) manipulation of DNA are similar, and distinct from Trichostatin A (TSA)-induced chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more similar to those of TSA than to DNMT1, DNMT3B, or double DNMT somatic cell knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days exposure, suggesting active demethylation or direct influence of both drugs on the stability of methylation and/or chromatin marks. Agents that induce gene activation through hypomethylation may have unintended consequences, since nearly as many genes were downregulated as upregulated after demethylation. In addition, a 75 kb cluster of metallothionein genes was coordinately regulated