scholarly journals Nuclear Morphology Optimized Deep Hybrid Learning (NUMODRIL) For Accurate Diagnosis and Prognosis of Ovarian Cancer

Author(s):  
Duhita Sengupta ◽  
Sk Nishan Ali ◽  
Aditya Bhattacharya ◽  
Joy Mustafi ◽  
Asima Mukhopadhyay ◽  
...  

Abstract Nuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyse the malignant potential of cancer cells. Considering the structural alteration of nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analysing immunohistochemistry images of tissue samples for diagnosing various cancers. Our aim is to study the morphometric distribution of nuclear lamin proteins as a specific parameter in ovarian cancer tissues. Besides being the principal mechanical component of the nucleus, lamins also present a platform for binding of proteins and chromatin thereby serving a wide range of nuclear functions like maintenance of genome stability, chromatin regulation. Altered expression of lamins in different subtypes of cancer is now evident from data across the world. It has already been elucidated that in ovarian cancer, extent of alteration in nuclear shape and morphology can determine degree of genetic changes and thus can be utilized to predict the outcome of low to high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and introduced a novel Deep Hybrid Learning approach on the basis of the distribution of lamin proteins. Although developed with ovarian cancer datasets in view, this architecture would be of immense importance in accurate and fast diagnosis and prognosis of all types of cancer associated with lamin induced morphological changes and would perform across small/medium to large datasets with equal efficiency.

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261181
Author(s):  
Duhita Sengupta ◽  
Sk Nishan Ali ◽  
Aditya Bhattacharya ◽  
Joy Mustafi ◽  
Asima Mukhopadhyay ◽  
...  

Nuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyze the malignant potential of cancer cells. Considering the structural alteration of the nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analyzing immunohistochemistry images of tissue samples for diagnosing various cancers. We aim to correlate the morphometric features of the nucleus along with the distribution of nuclear lamin proteins with classical machine learning to differentiate between normal and ovarian cancer tissues. It has already been elucidated that in ovarian cancer, the extent of alteration in nuclear shape and morphology can modulate genetic changes and thus can be utilized to predict the outcome of low to a high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and developed a dual pipeline architecture that combines the matrices of morphometric parameters with deep learning techniques of auto feature extraction from pre-processed images. This novel Deep Hybrid Learning model, though derived from classical machine learning algorithms and standard CNN, showed a training and validation AUC score of 0.99 whereas the test AUC score turned out to be 1.00. The improved feature engineering enabled us to differentiate between cancerous and non-cancerous samples successfully from this pilot study.


2020 ◽  
Author(s):  
Duhita Sengupta ◽  
Sk Nishan Ali ◽  
Aditya Bhattacharya ◽  
Joy Mustafi ◽  
Asima Mukhopadhyay ◽  
...  

AbstractNuclear morphological features are potent determining factors for clinical diagnostic approaches adopted by pathologists to analyse the malignant potential of cancer cells. Considering the structural alteration of nucleus in cancer cells, various groups have developed machine learning techniques based on variation in nuclear morphometric information like nuclear shape, size, nucleus-cytoplasm ratio and various non-parametric methods like deep learning have also been tested for analysing immunohistochemistry images of tissue samples for diagnosing various cancers. Our aim is to study the morphometric distribution of nuclear lamin proteins as a specific parameter in ovarian cancer tissues. Besides being the principal mechanical component of the nucleus, lamins also present a platform for binding of proteins and chromatin thereby serving a wide range of nuclear functions like maintenance of genome stability, chromatin regulation. Altered expression of lamins in different subtypes of cancer is now evident from data across the world. It has already been elucidated that in ovarian cancer, extent of alteration in nuclear shape and morphology can determine degree of genetic changes and thus can be utilized to predict the outcome of low to high form of serous carcinoma. In this work, we have performed exhaustive imaging of ovarian cancer versus normal tissue and introduced a novel Deep Hybrid Learning approach on the basis of the distribution of lamin proteins. Although developed with ovarian cancer datasets in view, this architecture would be of immense importance in accurate and fast diagnosis and prognosis of all types of cancer associated with lamin induced morphological changes and would perform across small/medium to large datasets with equal efficiency.Significance StatementWe have developed a novel Deep Hybrid Learning approach based on nuclear morphology to classify normal and ovarian cancer tissues with highest possible accuracy and speed. Ovarian cancer cells can be easily distinguished from their enlarged nuclear morphology as is evident from lamin A & B distribution pattern. This is the first report to invoke specific nuclear markers like lamin A & B instead of classical haematoxylin-eosin staining in an effort to build parametric datasets. Our approach has been shown to outperform the existing deep learning techniques in training and validation of datasets over a wide range. Therefore this method could be used as a robust model to predict malignant transformations of benign nuclei and thus be implemented in the diagnosis and prognosis of ovarian cancer in future. Most importantly, this method can be perceived as a generalized approach in the diagnosis for all types of cancer.


Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Zofia Łapińska ◽  
Michał Dębiński ◽  
Anna Szewczyk ◽  
Anna Choromańska ◽  
Julita Kulbacka ◽  
...  

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.


2021 ◽  
Author(s):  
Li Bo ◽  
Yan Xiong ◽  
Qiyi He ◽  
Xiaodong Yu ◽  
Bo Li ◽  
...  

Abstract The anti-tumor potential of animal toxins has fully attracted the attention of researchers. Snake venoms is a complex mixture of different components and has revealed high toxicity on normal and tumoral tissues or cells. The snake venom L-Amino-acid oxidase (svLAAO) has grown up to be a critical research target in molecular biology sciences and medicine sciences since widespread presence and various biological roles, including antitumor application. We found that Crotalus adamanteus (C. adamanteus) venom LAAO significantly decreased the viability of ovarian cancer cells and caused morphological changes preceded cell death. Cell experiments confirmed that C. adamanteus venom LAAO caused alterations of intrinsic or extrinsic apoptosis pathway-related genes in ovarian cancer cells. Animal experiments and histological analysis also proved that C. adamanteus venom LAAO could effectively inhibit the damage of ovarian cancer to tissues. The major apoptosis induction of C. adamanteus venom LAAO on ovarian cancer cells can be blocked by catalase, suggesting that the cytotoxicity of C. adamanteus venom LAAO on ovarian cancer cells was mainly mediated by H2O2. Our preliminary results revealed that C. adamanteus venom LAAO may induce apoptosis of ovarian cancer cells through the death receptor pathway and mitochondrial pathway. It is inferred that C. adamanteus venom LAAO will be some advantages in New Drug Research and Development of antitumor drugs in the future. Nevertheless, extra studies on the pharmacological actions and molecular mechanism of svLAAO in anti-cancer are necessary in order to better promote its application.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Karen A. Bailey ◽  
Yuliya Klymenko ◽  
Peter E. Feist ◽  
Amanda B. Hummon ◽  
M. Sharon Stack ◽  
...  

1981 ◽  
Vol 20 (2) ◽  
pp. 268-274
Author(s):  
Makoto YASUDA ◽  
Hiroaki INUI ◽  
Mitsui YOSHIOKA ◽  
Kazuhiko OCHIAI ◽  
Shogo TOKUDOME ◽  
...  

2020 ◽  
Author(s):  
Eric J. Devor ◽  
Jace R. Lapierre ◽  
Kimberly K. Leslie ◽  
David P. Bender

Abstract Objective: ES-2 ovarian cancer cells have long been reported to have originated from a primary clear cell carcinoma of the ovary presenting in a 47 year-old African American patient. Two recent publications have offered evidence calling both of these characteristics into question. Our objective was to further study this cell line using quantitative real-time PCR (qPCR) and mitochondrial DNA (mtDNA) sequencing in order to confirm or refute these inconsistencies.Results: qPCR assays on two characteristic loci, hepatocyte nuclear factor 1β (NHF-1β) and glutathione peroxidase 3 (GPX3), suggest that ES-2 are unusual clear cell carcinoma cells that appear more like high grade serous carcinoma than clear cell. Further, mtDNA haplotyping places the ancestral origin of the patient’s lineage in the Middle East or Europe and not Africa. These results are consistent with and support the conclusions of the two recent publications.


2013 ◽  
Vol 27 (9) ◽  
pp. 1429-1441 ◽  
Author(s):  
Aurélie Docquier ◽  
Aurélie Garcia ◽  
Julien Savatier ◽  
Abdel Boulahtouf ◽  
Sandrine Bonnet ◽  
...  

In hormone-dependent tissues such as breast and ovary, tumorigenesis is associated with an altered expression ratio between the two estrogen receptor (ER) subtypes. In this study, we investigated the effects of ERβ ectopic expression on 17β-estradiol (E2)-induced transactivation and cell proliferation in ERα-positive BG1 ovarian cancer cells. As expected, ERβ expression strongly decreased the mitogenic effect of E2, significantly reduced E2-dependent transcriptional responses (both on a stably integrated estrogen response element [ERE] reporter gene and on E2-induced mRNAs), and strongly enhanced the formation of ER heterodimers as evidenced by chromatin immunoprecipitation analysis. Inhibition by the ERα-selective ligand propyl pyrazole triol was less marked than with the pan-agonist (E2) or the ERβ-selective (8β-vinyl-estradiol) ligands, indicating that ERβ activation reinforced the inhibitory effects of ERβ. Interestingly, in E2-stimulated BG1 cells, ERβ was more efficient than ERα to regulate the expression of receptor-interacting protein 140 (RIP140), a major ERα transcriptional corepressor. In addition, we found that the RIP140 protein interacted better with ERβ than with ERα (both in vitro and in intact cells by fluorescence cross-correlation spectroscopy). Moreover, RIP140 recruitment on the stably integrated reporter ERE was increased upon ERβ overexpression, and ERβ activity was more sensitive to repression by RIP140. Finally, small interfering RNA-mediated knockdown of RIP140 expression abolished the repressive effect exerted by activated ERβ on the regulation of ERE-controlled transcription by estrogens. Altogether, these data demonstrate the inhibitory effects of ERβ on estrogen signaling in ovarian cancer cells and the key role that RIP140 plays in this phenomenon.


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