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Papers by Priya Ramanathan

Oncologie

Single-cell RNA sequencing (scRNA-seq) technology has made great strides in research over the las... more Single-cell RNA sequencing (scRNA-seq) technology has made great strides in research over the last decade. Data analysis has been aided by developments in bioinformatics tools and artificial intelligence, allowing biological and clinical researchers to get a deeper understanding of the different cell clusters and their dynamics within tumours. Combining conventional treatment modalities like chemotherapy and radiation with immunotherapy is a growing trend in cancer treatment. Hence, knowledge of the tumour microenvironment and the effect of each treatment modality on the TME, at a single cell level can provide treating clinicians with better clues for patient stratification and prognostication. With this knowledge, immunotherapy could become successful in treating a wide range of cancers, opening the path for the creation of even more effective treatment strategies. Despite the widespread availability of scRNA-seq technology, computational analysis and data interpretation are still ...

Molecular Biology Reports

Additional file 1: Figure S1. Representative FACS profile of CD markers expression in unprimed an... more Additional file 1: Figure S1. Representative FACS profile of CD markers expression in unprimed and primed DCs at various concentrations of SPAG9 (a) CD80 (b) CD86 (c) CD14 (d) CD83 (e) CD40 and (f) HLADR. Figure S2. (a) Representative FACS profile for CCR7 expression in SPDCs (b) Bar graph indicates the CCR7 expression in four patients (P7–P10) (c) Fluorescence Minus One (FMO) control for gating the FoxP3 + population.

Objective: We have made an attempt to identify inhibitors that are bound with Acrosin binding pro... more Objective: We have made an attempt to identify inhibitors that are bound with Acrosin binding protein (ACRBP/OY-TES-1) through In silico molecular docking studies. Methods: Modeling of ACRBP/OY-TES-1 was performed using Iterative Threading Assembly Refinement (I-TASSER) software. Docking calculations were carried out using Glide. Glide Score (GS core) was used to rank the ligands on the basis of their relative binding affinities. Results: Food and Drug Administration (FDA)-approved drugs were docked with ACRBP/OY-TES-1 to identify potent inhibitors. Leuprolide a decapeptide interacts with the protein at residues Tyr116, Gly421, Leu433, Asp480 and Gln483 with Glide score-14.188. Other compounds that showed high affinity to the protein are triptorelin, nafatarelin, goserelin and sincalide. Conclusion: The investigation concluded that these drugs could be used as potential inhibitors against ACRBP/OY-TES-1 in cancer treatment.

Clinical Biochemistry, 2016

Indoleamine 2, 3-Dioxygenase (IDO) catalyses the degradation of the essential amino acid tryptoph... more Indoleamine 2, 3-Dioxygenase (IDO) catalyses the degradation of the essential amino acid tryptophan leading to the production of immunosuppressive Kynurenine. In the present study, we developed a modified method for measurement of Kynurenine/ tryptophan (K/T) ratio in the cervical tissue using HPLC and investigated its relationship with the expression of IDO1 and 2 genes in the cervical tumor milieu. Design and Methods: Cervical cancer punch biopsy samples of 27 women who presented at the Cancer Institute (WIA) were used for detection of K/T ratio by HPLC as well as expression of IDO1 and 2 at the mRNA level by Realtime PCR after obtaining Institutional ethical committee approval. Results: The K/T ratio was elevated significantly in cancer cervix samples compared to normal cervix (p<0.05). IDO1 mRNA levels were up-regulated whereas IDO2 mRNA levels were down-regulated in cancer cervix compared to the normal cervix. A positive correlation was observed between IDO1 and K/T (p<0.05) that IDO1was responsible for the increase in K/T ratio. Conclusion: Our preliminary data indicates that the K/T ratio at the tissue level may be investigated reliably using HPLC, as an indirect measure of IDO1 gene expression and activity.

RSC Advances, 2015

The SrtA–LPXTG interaction plays a key role in transpeptidation reaction, cell wall and biofilm f... more The SrtA–LPXTG interaction plays a key role in transpeptidation reaction, cell wall and biofilm formations. This study explains the blocking of LEU interactions with SrtA will results as SrtA inhibitors through MD simulation and energy calculations methods.

Background Dendritic cell (DC)-based immunotherapy is capable of activating the immune system, an... more Background Dendritic cell (DC)-based immunotherapy is capable of activating the immune system, and in particular tumour-specific cytotoxic T lymphocytes (CTLs) to eradicate the tumour. However, major limitations are the availability of autologous tumour cells as antigenic source and the selection of antigen that may have potential to activate both CD8 + and CD4 + T cells in immune-specific manner. Recently, we reported the expression of sperm associated antigen 9 (SPAG9) that is associated with various types of malignancies including cervical cancer. We examined the recombinant human SPAG9 (rhSPAG9) as an antigenic source for generating efficient DCs to stimulate CD4 + and CD8 + T cell responses for future DCs-based vaccine trials in cervical cancer patients. Methods Human monocytes derived DCs were pulsed with different concentrations (250 ng/ml to 1000 ng/ml) of recombinant human SPAG9 (rhSPAG9) and evaluated for their phenotypic and functional ability. Subsequently, the efficacy ...

Objective Dendritic cells (DCs) are administered as immunotherapeutic adjuvants after the complet... more Objective Dendritic cells (DCs) are administered as immunotherapeutic adjuvants after the completion of standard treatment in most settings. However, our Phase I trial indicated that one patient out of four, who received autologous tumor lysate-pulsed dendritic cell (TLDC) also received cisplatin chemotherapy and experienced complete regression of her lung lesion, continuing to be disease free till date. Hence, the objective of our current study is to evaluate the sustenance or augmentation of immune responses when autologous human papillomavirus positive cervical tumor lysate pulsed DC- are combined with cisplatin, using co-culture assays in vitro. Methods Before treatment, peripheral blood and punch biopsy samples were collected from 23 cervical cancer patients after obtaining an informed consent. DC functionality was confirmed through phenotypic and functional assays using autologous peripheral blood mononuclear cells as responders. For cisplatin experiments, the drug was added a...

Background: Breast cancer is a major cause of cancer related death in women worldwide. Molecular ... more Background: Breast cancer is a major cause of cancer related death in women worldwide. Molecular diagnostic markers that are detectable in early-stage breast cancer can aid in effective clinical intervention. Circular RNAs are a recently identified group of non-coding RNA with potential role in cancer development and progression. In this study, we aimed to identify circular RNAs specific for early stage breast cancer. Method: Circular RNA expression profile was analyzed in early-stage breast cancer tissues (N=5), matched normal counterparts (N=5) and absolute normal samples (N=5) by RNA-sequencing that enables a comprehensive analysis of RNA expression across the transcriptome. Two different algorithms, find_circ and DCC were used to identify the differentially expressed circular RNAs. Results: A total of 58 and 87 circular RNAs were found to be differentially expressed by find_circ and DCC algorithms, respectively, among which 26 circular RNAs were common. Hsa_circ_0001946 (CDR1-as...

Human antibodies, 2019

BACKGROUND AND OBJECTIVE CD99/MIC2 gene product is a heavily glycosylated transmembrane protein w... more BACKGROUND AND OBJECTIVE CD99/MIC2 gene product is a heavily glycosylated transmembrane protein which plays a major role in homotypic cell adhesion, apoptosis of double positive T cells and vesicular protein trafficking. It is over expressed in various cancers and has been considered as an ideal therapeutic target. The present study focused at developing monoclonal antibodies against the extracellular domain (ECD) of CD99 using hybridoma technology. MATERIALS AND METHODS In order to generate monoclonal antibodies, the recombinant ECD of CD99 was used for immunizing the mice. Resulting hybridomas were screened through indirect ELISA. Clones which gave high absorbance values were sub cloned by limiting dilution followed by isotype determination, IP, WB and FACS. The monoclonal antibody 547F2 4F12 was purified from culture supernatant using FPLC and further screened using IF. Finally, the antibodies were validated for specificity using siRNA knock-down. RESULTS We were able to establis...

Scientific reports, Jan 3, 2017

The EWS-FLI1 chimeric protein uniquely expressed in Ewing's sarcoma has an obligate role in i... more The EWS-FLI1 chimeric protein uniquely expressed in Ewing's sarcoma has an obligate role in its aetiology. In our previous report we showed that ectopic expression of the DNA sequences form the junction region (a.a 251-280) can inhibit Ewing's sarcoma cell growth. In the present report, we introduced a peptide (TAT/NLS/EWS-PEP) comprising of thirty amino acids spanning the junction in conjunction with HIV-1-trans-activating (TAT) and nuclear localization signal sequence (NLS). Peptide uptake and localization studies revealed presence of peptide in ~99% of transduced cells and in the nucleus. Peptide transfection induced cytotoxicity relative to untreated and TAT-NLS peptide treated Ewing's sarcoma cells. The peptide inhibited clonogenicity, cell cycle, bromo-deoxy uridine (BrdU) uptake and invasion capacity of treated cells. The treatment also affected epithelial to mesenchymal transition (EMT) markers and EWS-FLI1 target gene expression levels. Co-immunoprecipitation ex...

Human Immunology, 2014

In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived matu... more In this study, we assessed the efficacy of tumor lysate primed and unprimed monocyte derived mature dendritic cells (DCs) to trigger an effective anti-tumor immune response in cervical cancer patients who tested positive for human papilloma virus (HPV) DNA. Lysate primed and unprimed DCs were assessed for the expression of CD80, CD86, CD40, HLADR and CD83. The ability of DCs to migrate in response to the chemokines CCL19 and 21 as well as their ability to secrete IL12p40 was investigated. Mixed lymphocyte proliferation assays were used to assess DC stimulatory capacity and their ability to generate a Th1 response. Our results showed no difference in phenotypic expression between primed and unprimed DCs but both had significantly increased expression of the activation marker CD83 when compared to immature DCs. Importantly, the primed DCs showed significant (p value = 0.03) IL-12p40 secretion and a superior migratory capacity towards CC19 and CCL21 (p value = 0.04) compared to unprimed DCs even after cytokine withdrawal. Primed DCs showed superior stimulation of T cell proliferation (allogeneic and autologous) and secretion of IFN gamma (IFN-c) than the unprimed DCs. Hence whole tumor lysate primed mature DCs could be potent immunotherapeutic adjuvants to standard treatment for cervical cancer.

Asian Pacific Journal of Cancer Prevention, 2014

Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in ... more Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms-saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.

Journal of Reproductive Immunology

Journal of Cellular and Molecular Medicine

Computational Biology and Chemistry

Current Problems in Cancer