Shikonin Causes Non-apoptotic Cell Death in B16F10 Melanoma.

BACKGROUND: Melanoma treatment is highly resistant to current chemotherapeutic agents. Due to its resistance towards apoptotic cell death, non-apoptotic cell death pathways are sought after. OBJECTIVE: We investigated a Chinese herbal medicine, shikonin, and its effect on B16F10 melanoma cells in vitro. METHODS: Cell growth of B16F10 melanoma cells treated with shikonin was analyzed using an MTT assay. Shikonin was combined with necrostatin, an inhibitor of necroptosis; caspase inhibitor; 3-methyladenine, an inhibitor of autophagy; or N-acetyl cysteine, an inhibitor of reactive oxygen species. Flow cytometry was used to assess types of cell death resulting from treatment with shikonin. Cell proliferation was also analyzed utilizing a BrdU labeling assay. Monodansylcadaverine staining was performed on live cells to gauge levels of autophagy. Western blot analysis was conducted to identify specific protein markers of necroptosis including CHOP, RIP1, and pRIP1. MitoTracker staining was utilized to identify differences in mitochondrial density in cells treated with shikonin. RESULTS: Analysis of MTT assays revealed a large decrease in cellular growth with increasing shikonin concentrations. The MTT assays with necrostatin, 3-methyladenine, and N-acetyl cysteine involvement, suggested that necroptosis, autophagy, and reactive oxygen species are a part of shikonin's mechanism of action. Cellular proliferation with shikonin treatment was also decreased. Western blotting confirmed that shikonin-treated melanoma cells increase levels of stress-related proteins, e.g., CHOP, RIP, pRIP. CONCLUSION: Our findings suggest that mainly necroptosis is induced by the shikonin treatment of B16F10 melanoma cells. Induction of ROS production and autophagy are also involved.

Metastatic Endometrioid Carcinoma Mimicking a Subungual Melanoma.

CASE: We report a case of a 76-year-old female with a stage IB, grade I endometrioid endometrial carcinoma who presented with right-hip pain and an enlarging black, exophytic, subungual lesion on her right-small-finger distal phalanx. Clinically, the distal phalanx lesion was suspicious for a subungual melanoma; however, advanced imaging suggested metastatic disease, with lesions in the acetabulum, lungs, brain, vulva, and vagina. CONCLUSION: Partial amputation of the right, small finger and vulvar biopsies confirmed an endometrial carcinoma. To our knowledge, this is the first described case of endometrial adenocarcinoma metastasis to the phalanx of an upper extremity, mimicking a subungual melanoma.

Erratum: First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector [Phys. Rev. Lett. 121, 051301 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector.

We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c^{2}. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 g d). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations.

Results from the Super Cryogenic Dark Matter Search Experiment at Soudan.

We report the result of a blinded search for weakly interacting massive particles (WIMPs) using the majority of the SuperCDMS Soudan data set. With an exposure of 1690 kg d, a single candidate event is observed, consistent with expected backgrounds. This analysis (combined with previous Ge results) sets an upper limit on the spin-independent WIMP-nucleon cross section of 1.4×10^{-44} (1.0×10^{-44}) cm^{2} at 46 GeV/c^{2}. These results set the strongest limits for WIMP-germanium-nucleus interactions for masses >12 GeV/c^{2}.

Prognostic significance of microscopic tumor burden in sentinel lymph node in patients with cutaneous melanoma.

BACKGROUND/AIM: Sentinel lymph node (SLN) biopsy provides useful prognostic information for patients with melanoma. The present study sought to determine the prognostic value of SLN tumor burden on overall survival (OS) and disease-free survival (DFS). We also assessed its association with non-sentinel lympth node (NSLN) involvement. PATIENTS AND METHODS: We conducted a retrospective review of 138 patients with cutaneous melanoma, who were found to have positive SLNs from 2000 to 2011. SLN tumor burden was measured in the maximum diameter of the largest tumor focus. OS and DFS were assessed by the Kaplan-Meier method and Cox proportional hazard regression model. A logistic regression model was used to evaluate the association between SLN tumor burden and NSLN positivity. RESULTS: On multivariable analysis, SLN tumor burden was significantly associated with OS (hazard ratio (HR)>1 vs. ≤ 1 mm=5.15; 95% confidence interval (CI)=2.32-11.44; p<0.0001) and DFS rate (HR>1 vs. ≤ 1 mm=3.02; 95% CI=1.37-6.67; p=0.0064). On univariate analysis, SLN tumor burden was significantly associated with NSLN positivity (OR>1 vs. ≤ 1 mm=3.41; 95% CI=1.03-11.27; p=0.04). CONCLUSION: SLN tumor burden, by measuring the maximum diameter of the largest tumor focus, is significantly associated with OS, DFS and NSLN involvement.

Tools for thoughtful action: the role of ecosystem approaches to health in enhancing public health.

The intimate interdependence of human health and the ecosystems in which we are embedded is now a commonplace observation. For much of the history of public health, this was not so obvious. After over a century of focus on diseases, their biologic causes and the correction of exposures (clean water and air) and facilitation of responses (immunizations and nutrition), public health discourse shifted to embrace the concept of determinants of health as extending to social, economic and environmental realms. This moved the discourse and science of public health into an unprecedented level of complexity just as public concern about the environment heightened. To address multifactorial, dynamic impacts on health, a new paradigm was needed which would overcome the separation of humans and ecosystems. Ecosystem approaches to health arose in the 1990s from a rich background of intellectual ferment as Canada wrestled with diverse problems ranging from Great Lakes contamination to zoonotic diseases. Canada's International Development Research Centre (IDRC) played a lead role in supporting an international community of scientists and scholars who advanced ecosystem approaches to health. These collective efforts have enabled a shift to a research paradigm that embraces transdisciplinarity, social justice, gender equity, multi-stakeholder participation and sustainability.

Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region.

Plexiform schwannoma is a rare variant of Schwann cell tumor. Occurring in either conventional or cellular type, they are characterized either grossly or histologically by a plexiform pattern of intraneural growth often with multinodularity. Ordinary as well as plexiform schwannoma typically arise in superficial soft tissues and show a predilection for the head and neck region. Infrequent examples arise in the setting of neurofibromatosis type 2 or schwannomatosis. The purpose of this study was to assess the frequency of plexiform schwannoma by location, to determine their syndromic association, and to analyze the clinicopathologic features of tumors affecting the head and neck region. It was found, in this not entirely random population, that plexiform schwannoma represented 4.3% of all schwannomas, 23% of head and neck region examples, 15% of cutaneous schwannomas, and lastly, 2% of 322 oral nerve sheath tumors made separately available for review. Furthermore, the association with neurofibromatosis type 2 and with schwannomatosis was 5% each.

Breast cancer risk in women with radial scars in benign breast biopsies.

BACKGROUND: The risk for subsequent breast cancer in women diagnosed with radial scar lesions (RS) on benign breast biopsy remains controversial. We studied the relative risk of radial scar lesions in a large cohort of patients with benign breast disease (BBD). METHODS: Radial scars were identified in a BBD cohort of 9,262 patients biopsied at Mayo Clinic between 1967 and 1991. Radial scar lesions were classified as proliferative disease without atypia (PDWA) unless atypia was present (classified as atypical hyperplasia [AH]). The observed number of breast cancers developing among those with RS was compared to that expected in the general population using standardized incidence ratios (SIRs, mean follow-up interval 17 years). RESULTS: RS were identified in 439 (4.7%) of the cohort members; 382 (87.0%) contained one RS, 42 (9.6%) contained two, 9 (2.0%) contained three, and 6 (1.4%) contained four or more. The majority of RS (356, 82.4%) were less than 5.0 mm in diameter; 60 (13.9%) were 5.0-9.9 mm, and 16 (3.7%) were 10.0 mm or greater. The relative risk for women with PDWA and RS was 1.88 (95% CI, 1.36-2.53), no different than PDWA without RS [relative risk 1.57 (95% CI, 1.37-1.79) (P=0.29)]. Women with atypical hyperplasia and RS (n=60) had a relative risk of 2.81 (95% CI, 1.29-5.35), while those with atypia but without RS had a relative risk of 3.97 (95% CI, 2.99-5.19). CONCLUSIONS: RS imparts no increased breast cancer risk above that of PDWA or AH without RS.

Pseudomycetoma caused by Microsporum canis in an immunosuppressed patient: a case report and review of the literature.

BACKGROUND: A 65-year-old woman with a history of liver and kidney transplantation presented with a pruritic and tender rash of 2-year duration on her left knee. METHODS: The patient had a physical examination, and multiple skin biopsies were performed. RESULTS: Examination showed a cluster of dome-shaped, violaceous papules. A skin biopsy specimen showed multiple granules containing basophilic material within the superficial to mid dermis. The grains were embedded in an eosinophilic substance and surrounded by granulomatous inflammation. A Gomori methenamine silver stain showed abundant septate hyphae, and cultures grew colonies of Microsporum canis. A diagnosis of dermatophytic granuloma, or pseudomycetoma, was made. After considering the patient's immune status, a prolonged course of fluconazole was initiated. CONCLUSION: Microsporum canis, a frequently encountered zoophilic dermatophyte associated with tinea capitis and tinea corporis, is rarely associated with a mycetoma-like presentation, grain formation, or systemic infection. The medical literature describes only six cases of M. canis causing mycetoma-like formations in immunocompromised and immunocompetent patients. This case report describes an unusual presentation of a common dermatophyte infection, and the literature review summarizes the importance of recognizing atypical presentations of dermatophyte infections. Such infections may warrant more aggressive treatment in immunocompromised patients.

Unusual presentation of a malignant granular cell tumor of the pelvis: case report and literature review.

BACKGROUND: Malignant granular cell tumors are among the rarest of soft tissue cancers, currently understood to be of Schwann cell origin. As with their benign counterparts, malignant granular cell tumors (MGCTs) have a wide anatomic distribution and carry a poor prognosis, with recurrence and metastasis typically within 1 year of diagnosis. Only a handful of MGCTs have been described in the pelvis. CASE: We describe a case of malignant granular cell tumor that presented as a pararectal mass associated with severe rectal pain. The patient underwent pelvic exenteration and postoperative radiation therapy. She recurred with evidence of liver metastases on imaging studies 8 months following her exenteration. CONCLUSION: We discuss the diagnosis and prognosis of malignant granular cell tumors arising in the pelvis.