ORCID Profile
0000-0001-8761-0837
Current Organisation
Monash University
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Publisher: Springer Science and Business Media LLC
Date: 12-11-2019
DOI: 10.1038/S41598-019-53147-9
Abstract: Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice ( n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice ( P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group ( P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.
Publisher: MDPI AG
Date: 20-07-2022
Abstract: State-of-the-art artificial intelligence (AI) has recently gained considerable interest in the healthcare sector and has provided solutions to problems through automated diagnosis. Cytological examination is a crucial step in the initial diagnosis of cancer, although it shows limited diagnostic efficacy. Recently, AI applications in the processing of cytopathological images have shown promising results despite the elementary level of the technology. Here, we performed a systematic review with a quantitative analysis of recent AI applications in non-gynecological (non-GYN) cancer cytology to understand the current technical status. We searched the major online databases, including MEDLINE, Cochrane Library, and EMBASE, for relevant English articles published from January 2010 to January 2021. The searched query terms were: “artificial intelligence”, “image processing”, “deep learning”, “cytopathology”, and “fine-needle aspiration cytology.” Out of 17,000 studies, only 26 studies (26 models) were included in the full-text review, whereas 13 studies were included for quantitative analysis. There were eight classes of AI models treated of according to target organs: thyroid (n = 11, 39%), urinary bladder (n = 6, 21%), lung (n = 4, 14%), breast (n = 2, 7%), pleural effusion (n = 2, 7%), ovary (n = 1, 4%), pancreas (n = 1, 4%), and prostate (n = 1, 4). Most of the studies focused on classification and segmentation tasks. Although most of the studies showed impressive results, the sizes of the training and validation datasets were limited. Overall, AI is also promising for non-GYN cancer cytopathology analysis, such as pathology or gynecological cytology. However, the lack of well-annotated, large-scale datasets with Z-stacking and external cross-validation was the major limitation found across all studies. Future studies with larger datasets with high-quality annotations and external validation are required.
Publisher: MDPI AG
Date: 10-03-2022
Abstract: This study aimed to assess the prognostic significance, assessment methods, and molecular features of tumor budding (TB). A literature search of Medline, EMBASE, Cochrane Library, and eleven cohort studies (seven cervical and four endometrial cancers) was conducted. Three assessment methods for TB involving 2009 patients were collected and constituted in the analysis. Our meta-analysis showed that TB was a marker of poor survival, regardless of the cancer origin site or assessment method (overall survival: hazard ratio [HR], 2.40 95% confidence interval [CI], 1.82–3.17 disease-free survival: HR, 3.32 95% CI, 2.46–4.48). In endometrial cancers, TB is associated with the epithelial–mesenchymal transition, microvessel density, and decreased hormone receptor expression. Thus, we suggest TB as a poor prognostic marker for all gynecologic cancers.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2019
DOI: 10.1007/S10067-019-04851-4
Abstract: Kikuchi-Fujimoto disease (KFD) is a rare benign lymphadenitis that mainly involves cervical lymph nodes of young Asian women with unknown etiology. Recently, we experienced a case of KFD found with Torque teno virus/Torque teno-like mini virus (TTV/TTMV) from a 26-year-old woman. TTV/TTMV is a genus of Circoviridae that causes necrotizing lymphadenitis in pigs, which shares the key histologic finding of KFD. The purpose of this study is to investigate the pathogenic role of TTV/TTMV in KFD by quantitative polymerase chain reaction (qPCR) analysis. We performed two-step qPCR specific to TTV/TTMV with formalin-fixed paraffin-embedded tissue of sequentially selected 100 KFD patients and 50 randomly selected, matched normal controls. Consequent direct sequencing was done for confirmation with PCR products. PCR lification of TTV and TTMV was found in a significantly higher proportion in KFDs than normal controls (TTV, 85% vs. 18%, p < 0.000 TTMV, 91% vs. 24%, p < 0.000). After the sequencing, KFD s les showed more sequence matching than control s les for TTMV (94% vs. 30%, p < 0.000). This finding strongly suggests the possible implication of TTV/TTMV in the pathogenesis of KFD. Animal or in vivo experimental design should be followed in the future.Key Points• Kikuchi-Fujimoto disease (KFD) is rare and its etiology is still unclear.• Torque teno/Torque teno-like minivirus (TTV/TTMV) is a recently introduced virus in the Circoviridae family that causes necrotizing lymphadenitis in pigs, histologically similar to KFD.• We discovered the significantly increased TTV/TTMV viral loads in the KFD patients than normal controls, which implicates TTV/TTMV in the pathogenesis of KFD.
Publisher: Springer Science and Business Media LLC
Date: 03-04-2019
DOI: 10.1038/S41598-019-42088-Y
Abstract: Amide proton transfer (APT) imaging is a novel molecular MRI technique to detect endogenous mobile proteins and peptides through chemical exchange saturation transfer. In this preliminary study, the purpose was to evaluate the feasibility of APT imaging in monitoring the early therapeutic response to nitroxoline (NTX) in a temozolomide (TMZ)-resistant glioblastoma multiforme (GBM) mouse model, which was compared with diffusion-weighted imaging (DWI). Here, we prepared TMZ-resistant GBM mouse model ( n = 12), which were treated with 100 mg/kg/day of NTX ( n = 4) or TMZ ( n = 4), or saline ( n = 4) for 7 days for the evaluation of short-term treatment by using APT imaging and DWI sequentially. The APT signal intensities and apparent diffusion coefficient (ADC) values were calculated and compared before and after treatment. Moreover, immunohistological analysis was also employed for the correlation between APT imaging and histopathology. The association between the APT value and Ki-67 labeling index was evaluated by using simple linear regression analysis. The short-term NTX treatment resulted in significant decrease in APT value as compared to untreated and TMZ group, in which APT signals were increased. However, we did not observe significantly increased mean ADC value following short-term NTX treatment. The Ki-67 labeling index shows a correlation with APT value. APT imaging could show the earlier response to NTX treatment as compared to ADC values in a TMZ-resistant mouse model. We believe that APT imaging can be a useful imaging biomarker for the early therapeutic evaluation in GBM patients.
Publisher: MDPI AG
Date: 24-05-2022
Abstract: Cancers with high microsatellite instability (MSI-H) have a better prognosis and respond well to immunotherapy. However, MSI is not tested in all cancers because of the additional costs and time of diagnosis. Therefore, artificial intelligence (AI)-based models have been recently developed to evaluate MSI from whole slide images (WSIs). Here, we aimed to assess the current state of AI application to predict MSI based on WSIs analysis in MSI-related cancers and suggest a better study design for future studies. Studies were searched in online databases and screened by reference type, and only the full texts of eligible studies were reviewed. The included 14 studies were published between 2018 and 2021, and most of the publications were from developed countries. The commonly used dataset is The Cancer Genome Atlas dataset. Colorectal cancer (CRC) was the most common type of cancer studied, followed by endometrial, gastric, and ovarian cancers. The AI models have shown the potential to predict MSI with the highest AUC of 0.93 in the case of CRC. The relatively limited scale of datasets and lack of external validation were the limitations of most studies. Future studies with larger datasets are required to implicate AI models in routine diagnostic practice for MSI prediction.
Publisher: MDPI AG
Date: 13-07-2020
Abstract: Colorectal cancer (CRC) is one of the most common cancers requiring early pathologic diagnosis using colonoscopy biopsy s les. Recently, artificial intelligence (AI) has made significant progress and shown promising results in the field of medicine despite several limitations. We performed a systematic review of AI use in CRC pathology image analysis to visualize the state-of-the-art. Studies published between January 2000 and January 2020 were searched in major online databases including MEDLINE (PubMed, Cochrane Library, and EMBASE). Query terms included “colorectal neoplasm,” “histology,” and “artificial intelligence.” Of 9000 identified studies, only 30 studies consisting of 40 models were selected for review. The algorithm features of the models were gland segmentation (n = 25, 62%), tumor classification (n = 8, 20%), tumor microenvironment characterization (n = 4, 10%), and prognosis prediction (n = 3, 8%). Only 20 gland segmentation models met the criteria for quantitative analysis, and the model proposed by Ding et al. (2019) performed the best. Studies with other features were in the elementary stage, although most showed impressive results. Overall, the state-of-the-art is promising for CRC pathological analysis. However, datasets in most studies had relatively limited scale and quality for clinical application of this technique. Future studies with larger datasets and high-quality annotations are required for routine practice-level validation.
Publisher: MDPI AG
Date: 09-11-2021
Abstract: Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34–1.76, p 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10–1.21, p 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03–1.08, p 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28–1.49, p 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10–1.33, p = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29–3.45, p = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94–5.58, p 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2020
DOI: 10.1186/S12885-020-6673-2
Abstract: Peri ullary cancers (PAC) including pancreatic, ulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient s les. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.
Publisher: MDPI AG
Date: 13-05-2022
Abstract: The integration of digital pathology (DP) with artificial intelligence (AI) enables faster, more accurate, and thorough diagnoses, leading to more precise personalized treatment. As technology is advancing rapidly, it is critical to understand the current state of AI applications in DP. Therefore, a patent analysis of AI in DP is required to assess the application and publication trends, major assignees, and leaders in the field. We searched five major patent databases, namely, those of the USPTO, EPO, KIPO, JPO, and CNIPA, from 1974 to 2021, using keywords such as DP, AI, machine learning, and deep learning. We discovered 6284 patents, 523 of which were used for trend analyses on time series, international distribution, top assignees word cloud analysis and subject category analyses. Patent filing and publication have increased exponentially over the past five years. The United States has published the most patents, followed by China and South Korea (248, 117, and 48, respectively). The top assignees were Paige.AI, Inc. (New York City, NY, USA) and Siemens, Inc. (Munich, Germany) The primary areas were whole-slide imaging, segmentation, classification, and detection. Based on these findings, we expect a surge in DP and AI patent applications focusing on the digitalization of pathological images and AI technologies that support the vital role of pathologists.
Publisher: MDPI AG
Date: 26-03-2021
DOI: 10.3390/DIAGNOSTICS11040597
Abstract: Peri ullary cancers (PACs) are characterized by tumor-infiltrating lymphocytes (TILs), severe fibrosis, and epithelial to mesenchymal transition (EMT). The immune checkpoint marker programmed death-1 (PD-1) and its ligands 1 and 2 have gained popularity in cancers with TILs. Evidence suggests a strong relationship between immune checkpoint markers and EMT in cancers. Here, we evaluated the expression and prognostic significance of immune checkpoint and EMT markers in PAC using an automated image analyzer. Formalin-fixed, paraffin-embedded surgically excised PAC tissues from laboratory archives (1998–2014) were evaluated by immunohistochemical staining for PD-1, PD-L1, and PD-L2 in a tissue microarray. In total, 115 PAC patients (70 males and 45 females) with an average age of 63 years were analyzed. Location, gross type, size, radial resection margin, N-M stage, lymphatic invasion, vascular invasion, perineural invasion, histologically well-differentiated severe inflammation, and high PD-L1 expression were significantly associated with recurrence. Higher PD-L1 expression, but not PD-1 and PD-L2, was significantly related to better overall survival (OS) and disease-free survival (DFS). PD-L1 and PD-L2 were significantly related to EMT markers. Aside from other clinicopathologic parameters, high PD-L1 expression was significantly related to better OS and DFS of PAC patients. Moreover, immune checkpoint markers were significantly associated with EMT markers. Therefore, PD-L1 expression can be a good prognostic marker to guide future immune target-based therapies in PAC patients.
Publisher: MDPI AG
Date: 15-06-2021
Abstract: Many pathogenic viral pandemics have caused threats to global health the COVID-19 pandemic is the latest. Its transmission is growing exponentially all around the globe, putting constraints on the health system worldwide. A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes this pandemic. Many candidate vaccines are available at this time for COVID-19, and there is a massive international race underway to procure as many vaccines as possible for each country. However, due to heavy global demand, there are strains in global vaccine production. The use of a plant biotechnology-based expression system for vaccine production also represents one part of this international effort, which is to develop plant-based heterologous expression systems, virus-like particles (VLPs)-vaccines, antiviral drugs, and a rapid supply of antigen-antibodies for detecting kits and plant origin bioactive compounds that boost the immunity and provide tolerance to fight against the virus infection. This review will look at the plant biotechnology platform that can provide the best fight against this global pandemic.
Location: Korea, Republic of
No related grants have been discovered for Nishant Thakur.