Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0-17), intermediat

Correlation of Oncotype DX Recurrence Score with Histomorphology and Immunohistochemistry in over 500 Patients

Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases (mean = 15%, median = 5%) and 2% of HER2+ cases were undervalued by Oncotype

A “Turn-On” thiol functionalized fluorescent carbon quantum dot based chemosensory system for arsenite detection

Carbon quantum dots (CQDs) have emerged out as promising fluorescent probes for hazardous heavy metals detection in recent past. In this study, water soluble CQDs were synthesized by facile microwave pyrolysis of citric acid & cysteamine, and functionalized with ditheritheritol to impart thiol functionalities at surface for selective detection of toxic arsenite in water. Microscopic analysis reveals that the synthesized CQDs are of uniform size (diameter ∼5 nm) and confirmed to have surface SH groups by FT-IR. The functionalized probe is then demonstrated for arsenite detection in water by “Turn-On” read out mechanism, which reduces the possibility of false positive signals associated with “turn off’ probes reported earlier. The blue luminescent functionalized CQDs exhibit increase in fluorescence intensity on arsenite addition in 5–100 ppb wide detection range. The probe can be used for sensitive detection of arsenite in environmental water to a theoretical detection limit (3s) of 0.086 ppb (R2 = 0.9547) with good reproducibility at 2.6% relative standard deviation. The presented reliable, sensitive, rapid fCQDs probe demonstrated to exhibit high selectivity towards arsenite and exemplified for real water samples as well. The analytical performance of the presented probe is comparable to existing organic & semiconductor based optical probes

A systematic review and meta-analysis of voltammetric and optical techniques for inorganic selenium determination in water

Selenium, a metalloid, commonly known for its essentiality has emerged out as a water pollutant of concern for environmentalist due to its presence in natural water resources above the permissible limit. The high level of selenium in the environment poses severe health and ecosystem threats, therefore, its monitoring in water is of paramount concern. The present contribution summarizes and critically analyzes the field promising techniques, in particular, voltammetry and optical approach, for selenium quantification in water. The role of sensor material (organic fluorophores, colorimetric dyes and quantum dots), electrode surface modifiers (Hg, Bi, polymers, nanomaterials, etc.), chelators, etc., to overcome various challenges and achieve better sensor performance in terms of detection limit, range, reproducibility, stability, selectivity, sensitivity, and so forth are critically discussed. To end with, the possible future developments are discussed towards the realization of a cost-effective & field deployable monitoring device for on-site selenium analysis

p53 Protein alterations in adult astrocytic tumors and oligodendrogliomas

Background: p53 is a tumor suppressor gene implicated in the genesis of a variety of malignancies including brain tumors. Overexpression of the p53 protein is often used as a surrogate indicator of alterations in the p53 gene. AIMS: In this study, data is presented on p53 protein expression in adult cases (>15 years of age) of astrocytic (n=152) and oligodendroglial (n=28) tumors of all grades. Of the astrocytic tumors, 86% were supratentorial in location while remaining 14% were located infratentorially - 8 in the the cerebellum and 13 in the brainstem. All the oligodendrogliomas were supratentorial. Materials and Methods: p53 protein expression was evaluated on formalin-fixed paraffin-embedded sections using streptavidin biotin immunoperoxidase technique after high temperature antigen retrieval. Results: Overall 52% of supratentorial astrocytic tumors showed p53 immunopositivity with no correlation to the histological grade. Thus, 58.8% of diffuse astrocytomas (WHO Grade II), 53.8% of anaplastic astrocytomas (WHO Grade III) and 50% of glioblastomas (WHO Grade IV) were p53 protein positive. In contrast, all the infratentorial tumors were p53 negative except for one brainstem glioblastoma. Similarly, pilocytic astrocytomas were uniformly p53 negative irrespective of the location. Among oligodendroglial tumors, - 25% in Grade II and 31.5% in grade III (anaplastic oligodendroglioma). Interestingly, p53 labeling index (p53 LI) did not correlate with the histopathological grade in both astrocytic and oligodendroglial tumors. Conclusions: Thus, this study gives an insight into the genetic and hence biological heterogeneity of gliomas, not only between astrocytic tumors vs. oligodendrogliomas but also within astrocytic tumors with regard to their grade and location. With p53 gene therapy trials in progress, this will possibly have future therapeutic implications

Ultrasensitive and Selective Sensing of Selenium Using Nitrogen-Rich Ligand Interfaced Carbon Quantum Dots

This work reports a label-free, ultrasensitive, and selective optical chemosensory system for trace level detection of selenite (SeO₃^2–), the most toxic form of selenium, in water. The probe, i.e., carbon quantum dots (CQDs), is designed from citric acid by means of pyrolysis and is interfaced with a newly synthesized nitrogen-rich ligand to create a selective sensor platform (functionalized CQDs, fCQDs) for selenite in a water matrix. Spectral (NMR, UV–vis, photoluminescence, Raman, and Fourier transform infrared analyses) and structural (high-resolution transmission electron microscopy) characteristics of the designed new probe were investigated. The developed sensor exhibits high sensitivity (limit of detection = 0.1 ppb), a wide detection range (0.1–1000 ppb range, relative standard deviation: 3.2%), and high selectivity even in the presence of commonly interfering ions reported to date, including Cl^–, NO₃^–, NO₂^–, Br^–, F^–, As­(V), As­(III), Cu²⁺, Pb²⁺, Cd²⁺, Zn²⁺, Sr²⁺, Rb²⁺, Na⁺, Ca²⁺, Cs⁺, K⁺, Mg²⁺, Li⁺, NH₄⁺, Co²⁺, etc. The observed selectivity is due to designed ligand characteristics in terms of strong Se–N chemistry. Ultrafast spectroscopic analysis of the fCQDs in the absence and presence of selenite was studied to understand the sensing mechanism. The sensor was successfully exemplified for real water samples and exhibits comparative performance to conventional ion channel chromatography as well as flame atomic absorption spectroscopy for selenite analysis. The promising results pave ways for realization of a field deployable device based upon a developed probe for selenite quantification in water

Immature natural killer cells promote progression of triple-negative breast cancer

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b-CD27- immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell-mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti-programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC