Small secretory proteins of immune cells can modulate gynecological cancers.

Small secretory proteins of immune cells are mostly Cytokines, which include chemokines, interleukins, interferons, lymphokines and tumor necrosis factors but not hormones or growth factors. These secretory proteins are the molecular messengers and primarily involved in autocrine, paracrine and endocrine signaling as immunomodulating agents. Hence, these proteins actually regulate the cells of immune system to communicate with one another to produce a synchronized, robust, still self-regulated response to a specific antigen. Chemokines are smaller secreted proteins that control overall immune cell movement and location; these chemokines are divided into 4 subgroups, namely, CXC, CC, CX3C and C according to the position of 4 conserved cysteine residues. Complete characterization of cytokines and chemokines can exploit their vast signaling networks to develop cancer treatments. These secretory proteins like IL-6, IL-10, IL-12, TNFα, CCL2, CXCL4 & CXCL8 are predominantly expressed in most of the gynecological cancers, which directly stimulate immune effector cells and stromal cells at the tumor site and augment tumor cell recognition by cytotoxic T-cells. Hence; these secretory proteins are the major regulators, which can actually modulate all kinds of gynecological cancers. Furthermore, advancements in adoptive T-cell treatment have relied on the use of multiple cytokines/chemokines to establish a highly regulated environment for anti-tumor T cell growth. A number of in vitro studies as well as animal models and clinical subjects have also shown that cytokines/chemokines have broad antitumor activity, which has been translated into a number of cancer therapy approaches. This review will focus on the foremost cytokines & chemokines involved in the majority of the gynecological malignancies and discuss their basic biology as well as clinical applications.

Picomolar Detection of Lead Ions (Pb2+) by Functionally Modified Fluorescent Carbon Quantum Dots from Watermelon Juice and Their Imaging in Cancer Cells.

Water contamination due to the presence of lead is one of the leading causes of environmental and health hazards because of poor soil and groundwater waste management. Herein we report the synthesis of functionally modified luminescent carbon quantum dots (CQDs) obtained from watermelon juice as potential nanomaterials for the detection of toxic Pb2+ ions in polluted water and cancer cells. By introducing surface passivating ligands such as ethanolamine (EA) and ethylenediamine (ED) in watermelon juice, watermelon-ethanolamine (WMEA)-CQDs and watermelon-ethylenediamine (WMED)-CQDs exhibited a remarkable ~10-fold and ~6-fold increase in fluorescence intensity with respect to non-doped WM-CQDs. The relative fluorescence quantum yields of WMEA-CQDs and WMED-CQDs were found to be 8% and 7%, respectively, in an aqueous medium. Among various functionally-modified CQDs, only WMED-CQDs showed high selectivity towards Pb2+ ions with a remarkably good limit of detection (LoD) of 190 pM, which is less than that of the permissible limit (72 nM) in drinking water. The functionally altered WMED-CQDs detected Pb2+ metal ions in polluted water and in a human cervical cancer cell line (HeLa), thus advocating new vistas for eco-friendly nanomaterials for their use as diagnostic tools in the environment and biomedical research areas.

A new class of teraryl-based AIEgen for highly selective imaging of intracellular lipid droplets and its detection in advanced-stage human cervical cancer tissues.

Lipid droplets (LDs) have drawn much attention in recent years. They serve as the energy reservoir of cells and also play an important role in numerous physiological processes. Furthermore, LDs are found to be associated with several pathological conditions, including cancer and diabetes mellitus. Herein, we report a new class of teraryl-based donor-acceptor-appended aggregation-induced emission luminogen (AIEgen), 6a, for selective staining of intracellular LDs in in vitro live 3T3-L1 preadipocytes and the HeLa cancer cell line. In addition, AIEgen 6a was found to be capable of staining and quantifying the LD accumulation in the tissue sections of advanced-stage human cervical cancer patients. Unlike commercial LD staining dyes Nile Red, BODIPY and LipidTOX, AIEgen 6a showed a high Stokes shift (195 nm), a good fluorescence lifetime decay of 12.7 ns, and LD staining persisting for nearly two weeks.

Noninvasive Point-of-Care Nanobiosensing of Cervical Cancer as an Auxiliary to Pap-Smear Test.

A potential cancer antigen (Ag), protein-phosphatase-1-gamma-2 (PP1γ2), with a restricted expression in testis and sperms has been identified as a biomarker specific to cervical cancer (CaCx). Detection of this cancer biomarker antigen (NCB-Ag) in human urine opens up the possibility of noninvasive detection of CaCx to supplement the dreaded and invasive Pap-smear test. A colorimetric response of an assembly of gold nanoparticles (Au NPs) has been employed for the quantitative, noninvasive, and point-of-care-testing of CaCx in the urine. In order to fabricate the immunosensor, Au NPs of sizes ∼5-20 nm have been chemically modified with a linker, 3,3'-di-thio-di-propionic-acid-di(n-hydroxy-succinimide-ester) (DTSP) to attach the antibody (Ab) specific to the NCB-Ag. Interestingly, the addition of Ag to the composite of Ab-DTSP-Au NPs leads to a significant hypsochromic shift due to a localized surface plasmon resonance phenomenon, which originates from the specific epitope-paratope interaction between the NCB-Ag and Ab-DTSP-Au NPs. The variations in the absorbance and wavelength shift during such attachments of different concentrations of NCB-Ag on the Ab-DTSP-Au NPs composite have been employed as a calibration to identify NCB-Ag in human urine. An in-house prototype has been assembled by integrating a light-emitting diode of a narrow range wavelength in one side of a cuvette in which the reaction has been performed while a sensitive photodetector to the other side to transduce the transmitted signal associated with the loading of NCB-Ag in the Ab-DTSP-Au NPs composite. The proposed immunosensing platform has been tested against other standard proteins to ensure noninterference alongside proving the proof-for-specificity of the NCB detection.