Biology subjects

Roy, P. K.

Publications and source records attributed to Roy, P. K..

4 recordsLinked to original sources

bioRxiv2025

Spontaneous cancer regression as inversion of spontaneous cancer progression: Malignant melanoma remission as a case-study towards clinical applicability

The spontaneous cancer regression process (SCR) a rather rare paradoxical natural phenomenon, shows that malignant tumors can episodically undergo complete permanent elimination without treatment, and thus may be used for gaining clues to incisive therapeutic innovations. SCR of malignant breast tumors occurs subclinically across human populations ([~]22% rate), according to Scandinavian and Wisconsin Screening Registries (monitoring 0.33million and 2.95million population respectively). SCR occurs in discoid melanomas ([~]12% rate). SCR process has high novelty with no toxicity nor recurrence, and duplicating SCR process is indeed clinically desirable. We aim to probe SCR using melanoma as illustrative pilot-study, and identify candidate leads that may mimic SCR on the tumor. We investigated molecular biological of melanoma, finding two reciprocal phases: spontaneous-progression and spontaneous-regression, and showed driver genes for melanoma SCR. Then, we pursued network pharmaco-informatics analysis. We found that spontaneous melanoma eradication shows an unexpected finding, in distinct contrast to the prevalent view that immunological processes and immunotherapy are critical for melanoma regression, than targeting DNA. We found that in contradistinction, it is DNA interference process that is primary route for melanoma regression, while anti-tumor immune activation is only secondarily needed. We observed that targeting two pathways (kinase-system, inositide-system) by inhibiting two genes, arrested melanoma-progression phase, and activated the reverse phase, melanoma-regression. We investigated the interactions of possible candidate leads, indicating significant therapeutic potency. Our findings underscore the high impact possibility for leveraging the anomalous phenomenon of spontaneous cancer regression as a general oncological principle for probing targeted therapeutic interventions, with substantial clinical potentials.

cancer biology↗

bioRxiv2025

Deciphering a common code: Unitary gene profile factor enabling Spontaneous Tumor Regression

Spontaneous-remission of Cancer (SRC), well documented in humans, is the paradoxical process of natural permanent tumor elimination by host-tissue system without any toxicity, recurrence or cancer stem-cell formation. This rare biological phenomenon is usually associated with immune activation, apoptosis, tumor microenvironment as well as oncogenic suppression. Thus, to understand this strikingly complex event, it is utmost important to look into the genetic and molecular landscape in-depth. Majorly, cancer mortalities occur due to epithelial tumors, hence, to find out the contributing pathways involved we interrogated epithelial malignancies: Neuroblastoma (neural-crest tissue), and Melanoma (skin tissue). Neuroblastoma, the most prevalent tumor type in newborns, arises from embryonic nerve cells and have a very diverse clinical trajectory. Similarly, Melanoma another common skin tumor, developed from malignant transformation of melanocytes (cells producing melanin pigment). It is well-known that in numerous patients, both these malignant tumors spontaneously regress permanently, while in others, these tumors escalate to fatality. We investigated microarray expression of spontaneous regression of malignant neuroblastoma tumors (n=498), the patients having 4 temporal stages (S1-S2-S3-S4), and malignant melanoma tumors (n=22) having 4 time points (T1-T2-T3-T4) [i.e. total 520 patients, each 8 remission-route steps]. We studied differentially expressed genes (DEGs) common in both regressing Neuroblastoma and Melanoma, and analyzed the protein-protein interactions (PPI) as well as protein-miRNA networks. One crucial ubiquitous gene factor was found across each stage of both the regressing tumors. This focal gene codes for a spectrin-repeat protein which acts as a linker between nucleus-cytoskeleton, and aids in maintaining normal cells nuclear and cellular integrity (demarcated as a significant morphological change in tumor cells) by abetting the formation of Mut-S complex, which is a significant player in mis-match repair pathway. Strikingly, both this protein and miRNA were found to be commonly targeting PIK3CA protein through separate paths. We endeavor to unravel the mechanism of action and decipher the common gene factors across the entire tumor regression process in both Neuroblastoma and Melanoma. We meticulously identified the underlying biological pathways responsible for spontaneous regression. These results provide insights into the molecular genetics and underlying pathophysiology of SCR in Neuroblastoma and Melanoma, suggesting a role for precision therapeutics in the future that can help mimic this extraordinary prodigy by targeting the uniform factors mentioned in this study.

cancer biology↗

bioRxiv2025

Unveiling the secrets of brain resilience: Multimodal neuroimaging insights into Neural dynamics and neuroprotection in ageing

With the onset of ageing the likelihood of brain degeneration increases but so does the remarkable capability of the brain to reorganize itself termed as neurocognitive resilience. Leveraging the neuroimaging mapped anatomical signatures to demarcate age related alteration of an individual brain is a promising strategy to identify ageing phenotypes and estimate the molecular cues account for coping mechanisms. This study endeavour to identifying neuroprotective signatures using multimodal structural and functional brain scans of healthy aged male and female cohort across dorsal-ventral pathways of neuronal signal processing. To obtain multifarious insight across numerous patho physiological process we employed cutting edge approaches such as structural magnetic resonance imaging (MRI): diffusion tensor imaging (DTI), functional MRI (fMRI) and vascular MRI (cerebrovascular reactivity). From the study we obtained several unexpected anatomical and physiological neuro-protective features in the older cohort. Overall, we observed that older cohort exhibit better circum-cerebral structural connectivity as (i) cuneus to superior frontal gyrus (ii) superior frontal gyrus to inferior frontal gyrus (iii) inferior temporal gyrus to inferior frontal gyrus and (iv) cuneus to inferior temporal gyrus. Another, significant neuroprotective anatomical signature was revealed, namely a connectivity through vertical occipital fasciculus across cuneus to temporal cortex in male and female older cohort. Additionally, in older female we observed a pronounced increment in overall functional connectivity network observed in inferior frontal gyrus (both hemispheres). Whereas in older male a substantial increment of functional connectivity network in cuneus was observed as compared to their younger counterpart.

neuroscience↗

bioRxiv2024

A three-dimensional histological cell atlas of the developing human brain

The human brain is believed to contain a full complement of neurons by the time of birth together with a substantial amount of the connectivity architecture, even though a significant amount of growth occurs postnatally. The developmental process leading to this outcome is not well understood in humans in comparison with model organisms. Previous magnetic resonance imaging (MRI) studies give three-dimensional coverage but not cellular resolution. In contrast, sparsely sampled histological or spatial omics analyses have provided cellular resolution but not dense whole brain coverage. To address the unmet need to provide a quantitative spatiotemporal map of developing human brain at cellular resolution, we leveraged tape-transfer assisted serial section histology to obtain contiguous histological series and unbiased imaging with dense coverage. Interleaved 20 thick Nissl and H&E series and MRI volumes are co-registered into multimodal reference volumes with 60 isotropic resolution, together with atlas annotations and a stereotactic coordinate system based on skull landmarks. The histological atlas volumes have significantly more contrast and texture than the MRI volumes. We computationally detect cells brain-wide to obtain quantitative characterization of the cytoarchitecture of the developing brain at 13-14 and 20-21 gestational weeks, providing the first comprehensive regional cell counts and characterizing the differential growth of the different brain compartments. Morphological characteristics permit segmentation of cell types from histology. We detected and quantified brain-wide distribution of mitotic figures representing dividing cells, providing an unprecedented spatiotemporal atlas of proliferative dynamics in the developing human brain. Further, we characterized the abundance and distribution of Cajal-Retzius cells, a transient cell population that plays essential roles in organizing glutamatergic cortical neurons into layers. Together, our study provides an unprecedented quantitative window into the developing human brain and the reference volumes and coordinate space should be useful for integrating spatial omics data sets with dense histological context.

neuroscience↗