In this study, we tried to find out the cytological relevance of cannibalism as a dependable feature of malignancy in effusion and urine cytology. We randomly selected a total of 40 cases consisting of 10 each of malignant effusion, benign effusion, malignant urine samples, and benign urine samples. These smears were assessed for the presence of cell cannibalism. The number of cannibalistic cells/100 tumor cells was counted. The cannibalistic cells were seen more commonly in malignant effusion cases (3.4/100 cells) compared with malignant urine cases (2/100 cells). There was not a single cannibalistic cell in benign conditions. The finding of an increased number of cannibalistic cell was highly significant in malignant versus benign samples (P > 0.0000, Student's t-test). The present study highlights the significance of cannibalism in malignant urine and effusion cytology. We suggest that cell cannibalism is a dependable cytological feature of malignancy.
Recent data show that increases in bradykinin (BK) concentration contribute to the beneficial effects of angiotensin-converting enzyme inhibitor (ACEI) treatment in chronic kidney disease. However, the possible role of BK in attenuated proteinuria, often seen in ACEI-treated patients, is not well studied. Here, we report that BK decreases mouse podocyte permeability through rearrangement of the tight junction protein zonula occludens-1 (ZO-1) and identify some of the major signaling events leading to permeability change. We show that BK2 receptor (BK2R) stimulation transactivates the epidermal growth factor receptor (EGFR). EGFR transactivation is mediated by a disintegrin and metalloenzyme (ADAM) family members, which are required for both extracellular signalregulated kinase (ERK) and EGFR activation by BK. Using a genesilencing approach we observed that both BK-induced ERK activation and BK-induced permeability decrease in podocytes is attenuated by ADAM17 down-regulation, and we identified epiregulin (ER) as the EGFR ligand participating in ADAM-dependent BK2R-EGFR cross-talk. EGFR inhibition attenuated both ZO-1 rearrangement and BK-induced permeability decreases in podocyte. We propose that ZO-1 redistribution is an important element of BK-induced permeability change and the signaling events involved in ZO-1 rearrangement include transactivation of the EGFR via ADAM17 activation and ER shedding. Our data indicate that ADAM17 and the EGFR may be potential novel therapeutic targets in diabetic nephropathy and other chronic kidney diseases.
Alteration of chromatin pattern is one of the most important clues to detect the malignant cell. However, the exact cause of change of chromatin pattern still is not clearly known. Recently, in last 20 yr, modern advanced technologies, such as fluorescent in situ hybridization (FISH), chromosome painting, green fluorescent protein (GFP) fusion technology, fluorescent recovery after photobleaching (FRAP), confocal microscopy, and multicolor four-dimensional imaging of living cell, have unfolded the mystery of the chromatin structure and dynamics. In this study, I have discussed the possible causes of chromatin change in malignant cells based on available recent information. Multiple factors are responsible for alteration of chromatin pattern in malignant cells. The important factors in this respect are chromatin relocation, DNA aneuploidy, change of nuclear matrix protein (NMP), histone protein alteration, abnormal nuclear lamin-chromatin interaction, and nuclear pore dysfunction. It is not impossible that the chromatin pattern alteration may be just a secondary change due to the interaction of fixative with chromatin and nonchromatinic substances in the nucleus.
Effective treatments for cancer are still needed, both for cancers that do not respond well to current therapeutics and for cancers that become resistant to available treatments. Herein we investigated the effect of a structure-selective d-amino acid peptide wrwycr that binds replication fork mimics and Holliday Junction (HJs) intermediates of homologous recombination (HR) in vitro, and inhibits their resolution by HJ-processing enzymes. We predicted that treating cells with HJ-binding compounds would lead to accumulation of DNA damage. As cells repair endogenous or exogenous DNA damage, collapsed replication forks and HJ intermediates will accumulate and serve as targets for the HJ-binding peptides. Inhibiting junction resolution will lead to further accumulation of DNA breaks, eventually resulting in amplification of the damage and causing cell death. Both peptide wrwycr and the related wrwyrggrywrw entered cancer cells and reduced cell survival in a dose- and time-dependent manner. Early markers for DNA damage, γH2AX foci and 53BP1 foci, increased with dose and/or time exposure to the peptides. DNA breaks persisted at least 48 h, and both checkpoint proteins Chk1 and Chk2 were activated. The passage of the cells from S to G2/M was blocked even after 72 h. Apoptosis, however, was not induced in either HeLa or PC3 cells. Based on colony-forming assays, about 35% peptide-induced cytotoxicity was irreversible. Finally, sublethal doses of peptide wrwycr (50–100 µM) in conjunction with sublethal doses of several DNA damaging agents (etoposide, doxorubicin, and HU) reduced cell survival at least additively and sometimes synergistically. Taken together, the results suggest that the peptides merit further investigation as proof-of-principle molecules for a new class of anti-cancer therapeutics, in particular in combination with other DNA damaging therapies.
Merkel cell carcinoma is a rare tumor of the skin and is found in the dermis of the elderly patient. 1,2 This neoplasm is slightly more common in women (male/female [M/F] ratio, 1.5:1). Its usual location is on the head and neck and extremities. 3,4 Fine-needle aspiration cytology (FNAC) of Merkel cell carcinoma has been described rarely in the literature and it is a possible source of mistaken diagnosis on FNAC. 5-7 Here, we describe the cytological features of one such tumor along with a possible differential diagnosis. A 58-year-old male patient presented with a 1-cm diameter ulcerated lesion over the left side of his forehead for 1-mo duration. He also had multiple 2-to 3-cm diameter lymph nodes in the left upper deep cervical region for some duration. The patient was referred to us for FNAC of the skin lesion and lymph node.FNAC was performed from both the skin lesion and the cervical lymph nodes with the help of a 5-cc syringe and needle. Both alcohol-fixed and air-dried smears were prepared for hematoxylin and eosin stain and May-Grunwald-Giemsa stain. FNAC smears from the skin lesion showed abundant cellularity. The cells were distributed predominantly singly. No specific arrangement of the cells was seen. Individual cells were round to oval with monomorphic nuclei, fine chromatin, and inconspicuous nucleoli (Fig. 1). FNAC smears of the lymph node show similar cytological features. Considering the overall cytological and clinical features, we diagnosed this tumor as a malignant round cell tumor with metastasis in the cervical lymph nodes. Possibilities were considered as peripheral neuroectodermal tumor and malignant adenxal tumor. Histopathology of the lesion was advised for a more definitive diagnosis. Subsequently, the skin lesion was excised and histopathological examination was performed. Histology section showed a malignant tumor in the dermis. The tumor cells were present as infiltrating islands and cords. The tumor cells replaced adenexal structures and infiltrated the subcutaneous tissue. The individual cells showed a monotonous uniform round nucleus with finely dispersed chromatin and inconspicuous nucleoli. The malignant cells showed chromogranin and cytokeratin positivity, which was seen as a characteristic perinuclear dot-like pattern. Based on the morphological features coupled with immunohistochemical findings, a diagnosis of Merkel cell carcinoma was offered. Subsequently, neck dissection of the cervical lymph nodes was performed and 9 of 21 lymph nodes showed metastasis.Merkel cell carcinoma usually is a locally aggressive and rare tumor. This tumor is presumed to be neuroendocrine in origin. 2,6 There are a few case reports of this tumor in cytology literature. [5][6][7] In this index case, the differential diagnosis was considered as non-Hodgkin's lymphoma, rhabdomyosarcoma, metastatic small-cell carcinoma, basalcell carcinoma of the skin, neuroectodermal tumors, and malignant melanoma. Absence of lymphoglandular bodies on FNAC smears rules out the possibility of non-Hodgkin's lymphoma....
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.