Low dose arsenite confers resistance to UV induced apoptosis via p53-MDM2 pathway in ketatinocytes

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Lysine demethylase KDM2A inhibits TET2 to promote DNA methylation and silencing of tumor suppressor genes in breast cancer

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Radiation induced angiosarcoma of the breast: outcomes from a retrospective case series

Abstract

Background

Radiation induced angiosarcoma (RIAS) of the breast is a rare and aggressive complication of radiotherapy. Due to the rarity of this disease, much of the evidence for its management is based on case reports or small retrospective series. We sought to describe the management and outcomes of RIAS in a large single-institution series.

Methods

All patients diagnosed with RIAS between January 2000 and January 2014 were identified from an institutional database.

Results

A total of 49 patients were identified. Median age at diagnosis was 72 years (range 51–93). Median time from completion of radiotherapy to diagnosis of RIAS was 7.5 years. Median tumour size at presentation was 5.0 cm (1.5–19.0). The majority of patients presented with localised disease (47, 95.9%). Of these, 35 (74.5%) were suitable for surgery and underwent surgery with curative intent. Twelve patients presented with localised irresectable disease. Of these, 7 received systemic chemotherapy, with a sufficient response to facilitate surgery in 3 patients. Following potentially curative surgery, 2-year local recurrence-free was 55.2%. Survival was significantly prolonged in patients presenting with resectable disease (2-year overall survival 71.1% vs 33.3%, p < 0.001). Tumour size >5 cm was prognostic of distant metastases-free survival and overall survival.

Conclusion

RIAS are rare, aggressive soft-tissue lesions with limited treatment options and high-rates of both local and systemic relapse.

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Tolerability and efficacy of concurrent chemoradiotherapy comparing carboplatin/paclitaxel versus platinum/5-FU regimen for locally advanced esophageal and esophagogastric junction cancers

Abstract

Platinum/5-fluorouracil (PF) is commonly used for chemoradiotherapy (CRT) for locally advanced esophageal and esophagogastric junction (EGJ) cancers. Weekly carboplatin and paclitaxel (CP) regimen for preoperative CRT has increased in popularity due to its potentially less toxicity. We retrospectively compared the tolerability and efficacy of these regimens. Patients with esophageal and EGJ squamous cell carcinoma (SCC) or adenocarcinoma who received CRT with curative intent were included. Safety and tolerability during CRT were evaluated using the CTCAE version 4.0. Efficacy was analyzed using pathologic complete response, disease-free survival, and overall survival. One hundred and twenty-four patients were eligible for analysis (CP = 64, PF = 60). Most patients had esophageal cancer (97%) with SCC histology (91%). Preoperative CRT was planned for 43% of patients in the CP group and 34% in the PF group (p = 0.306). The relative dose intensities of cisplatin (67.0%) and 5-fluorouracil (81.4%) were lower than those of carboplatin (86.6%) and paclitaxel (86.2%). No difference in the radiotherapy dose, hospitalization, interruption, or termination was observed between the groups. Dose reduction of chemotherapy was more frequent in the CP group (38 vs. 19%; p = 0.015). Febrile neutropenia was more frequent in the PF group (8 vs. 0%; p = 0.058). All-grade nausea/vomiting was lower in the CP group (20 vs. 38%; p = 0.032). Efficacy was comparable between both regimens. In the multivariate analysis, the CRT regimen was not a significant predictor of survival. The CP regimen had less toxicity than the PF regimen, while efficacy was comparable. A large prospective randomized study is warranted to confirm these results.

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The concept of platinum sensitivity could be applied to recurrent cervical cancer: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group

Abstract

Purpose

This study aimed at evaluating the applicability of the concept of platinum sensitivity to recurrent cervical cancer.

Methods

The clinical information of patients with recurrent cervical cancer, who were initially treated with platinum-based chemotherapy and received second-line platinum-based chemotherapy at the time of recurrence between January 2008 and December 2012, was retrospectively reviewed.

Results

A total of 677 patients from 71 medical centers were analyzed. The median overall survival (OS) for patients with platinum-free interval (PFI) of <6, 6–11, 12–17, and ≥18 months was 12.1 (95% CI 11.0–14.1) months, 17.4 (15.5–20.4) months, 20.2 (17.9–27.6) months, and 29.9 (26.7–36.0) months, respectively (P < 0.0001, log-rank). The best cut-off value of PFI that affected OS was 7 months, analyzed by the minimum P value method. The median progression-free survival (PFS) for patients with less than and more than PFI of 7 months was 6.2 months (95% CI 4.8–9.3) and 21.0 months (18.9–24.8) (P < 0.0001, log-rank), respectively, and the median OS for patients with less than and more than PFI of 7 months was 12.3 months (11.2–14.1) and 24.2 months (20.8–25.8) (P < 0.0001, log-rank). Multivariate analysis revealed that PFI (P < 0.0001, HR 0.449, 95% CI 0.369–0.548) alone had a statistically significant association with OS.

Conclusions

This study showed that the concept of platinum sensitivity could be applied to recurrent cervical cancer and PFI could be one of the independent prognostic factors for patients with recurrent cervical cancer who have previously been treated with platinum-based chemotherapy.

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Cancers, Vol. 9, Pages 102: Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

Cancers, Vol. 9, Pages 102: Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression

Cancers doi: 10.3390/cancers9080102

Authors: Ken-ichi Takayama Aya Misawa Satoshi Inoue

The androgen receptor (AR) plays important roles in prostate cancer development and prostate tumor growth. After binding to androgens, AR functions as a nuclear receptor and translocates to the nucleus to bind to specific AR-binding sites (ARBSs). AR regulates epigenetic factor recruitments to activate its downstream signaling. Although androgen deprivation therapy (ADT) is initially useful for prostate cancer patients, most patients eventually show resistance with hormone-refractory prostate cancers (HRPCs) or castration-resistant prostate cancers (CRPCs). Thus, new therapeutic strategies targeting HRPCs/CRPCs should be very important for clinical medicine as well as prostate cancer biology. Past studies have shown that mechanisms such as AR overexpression, hypersensitivity, variants and reprograming are responsible for developing HRPCs/CRPCs. These findings suggest that AR target genes will be major key factors. In this review article, we focus mainly on the androgen-regulated microRNAs (miRNAs) to summarize the contribution of miRNA-mediated pathways for prostate cancer progression.

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MACF1, a novel potential target in cancer

Abstracts

Cancer is a polygenic disease characterized by uncontrolled growth of normal body cells, which exhibits deregulation of cell cycle as well as resistance to apoptosis and leads to metastasize into other parts of the body. The spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1) plays an essential function in various cellular processes including cell proliferation, migrations, signaling transduction and embryo development. MACF1 is also involved in processes such as metastatic invasion in which cytoskeleton organization is a critical element that contributes to tumor progression in various human cancers. Aberrant expression of MACF1 initiates the tumor cell proliferation, migrations and metastasis in numerous cancers such as breast cancer, colon cancer, lung cancer and glioblastoma. In this review, we summarized the current knowledge of MACF1 and its critical role in different human cancer. It will be helpful for researchers to investigate the novel functional role of MACF1 in human cancers and as a potential target that enhances the efficacy of therapeutic treatment modalities.

This article is protected by copyright. All rights reserved.

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