Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

Association of Cutibacterium acnes with human thyroid cancer.

Introduction: The diverse subtypes of thyroid carcinoma have distinct clinical outcomes despite a comparable spectrum of underlying genetic alterations. Beyond genetic alterations, sparse efforts have been made to characterize the microbes associated with thyroid cancer. In this study, we examine the microbial profile of thyroid cancer. Methods: We sequenced the whole transcriptome of 70 thyroid cancers (40 papillary and 30 anaplastic). Using Infectious Pathogen Detector IPD 2.0, we analysed the relative abundance of 1060 microbes across 70 tumours from patients with thyroid cancer against 118 tumour samples from patients with breast, cervical, colorectal, and tongue cancer. Results: Our analysis reveals a significant prevalence of Cutibacterium acnes in 58.6% thyroid cancer samples compared to other cancer types (p=0.00038). Immune cell fraction analysis between thyroid cancer samples with high and low Cutibacterium loads identify enrichment of immunosuppressive cells, including Tregs (p=0.015), and other anti-inflammatory cytokines in the tumour microenvironment, suggesting an immune evasion/immunosuppression milieu is associated with the infection. A higher burden of Cutibacterium acnes was also found to be associated with poor survival defining a distinct sub-group of thyroid cancer. Conclusion: Cutibacterium acnes is associated with immune suppression and poor prognosis in a subpopulation of thyroid cancer. This study may help design novel therapeutic measures involving appropriate antibiotics to manage the disease better.

BODIPY-Based Mitochondrial Targeted NIR-Responsive CO-Releasing Platform for the On-Demand Release of CO to Treat Cancer.

It is an established fact that cancer is one of the most serious public health issues after coronary artery disease. Thus, exploring more effective and efficient therapeutic protocols over the traditional chemotherapeutic strategy is imperative to improving cancer survivorship and patient quality of life. In this respect, recent reports on molecularly engineered meso-substituted BODIPY have shown remarkable effects as a photoresponsive CO-releasing platform for the on-demand release of CO to treat cancer. Herein, we designed and synthesized two meso-substituted BODIPY photoresponsive CO-releasing molecules (photoCORMs). These BODIPY derivatives were tethered to a phenoxymethylpyridine moiety and oligoethylene glycol to maintain a hydrophilic-hydrophobic balance and improved cell permeability. The cell imaging experiments demonstrated that oligoethylene glycol containing photoCORM-1 efficiently internalized and preferentially localized at the mitochondria. To understand the mechanistic aspect of preferential localization into the mitochondria, live cell imaging was also carried out. Photorelease of CO was directly monitored by the inline IR spectroscopic technique. Finally, in vitro cytotoxicity and apoptosis assays on MDA-MB-231 cell lines clearly showed that photoCORM-1 induced apoptosis-mediated cell killing on account of photoreleased CO, which otherwise showed insignificant toxicity even at a very high concentration of ∼50 µM.

Neoadjuvant chemotherapy in a rare type of very locally advanced sinonasal carcinomas - long-term results from a tertiary care centre.

Introduction: Sinonasal carcinomas are a rare type of head and neck malignancy with various histologies. The outcomes of patients with unresectable locally advanced sinonasal carcinomas are poor. Hence, we performed this analysis to study the long-term outcomes of sinonasal adenocarcinoma (SNAC) and sinonasal undifferentiated carcinomas (SNUC) where neoadjuvant chemotherapy (NACT) has been given followed by local therapy. Methods: 16 patients with SNUC and adenocarcinoma who received NACT were found eligible for the study. Descriptive statistical analysis was performed for baseline characteristics, adverse events and treatment compliance. Kaplan Meir methods were used for the estimation of progression-free survival (PFS) and overall survival (OS). Results: Seven (43.75%) adenocarcinoma and nine (56.25%) SNUC patients were identified. The median age of the whole cohort was 48.5 years. The median number of cycles delivered was 3 (IQR 1-8). The incidence of grade 3-4 toxicity (CTCAE version 5.0) was 18.75%. The response was partial response or better in seven patients (43.75%). Post-NACT 11 patients (n = 15, 73%) were eligible for definitive therapy. The median PFS was 7.63 months (95% CI, 3.23 - NA months) and the median OS was 10.6 months (95% CI, 5.2-51.5 months). Median PFS and OS for those who underwent surgery post-NACT versus those who did not undergo surgery were 36.267 versus 3.7 months (p = 0.012) and 51.5 versus 10.633 months (p = 0.190), respectively. Conclusion: The study shows a favourable role of NACT in improving resectability, significant improvement in PFS and non-significant improvement in OS after surgery.

Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against fimbriae (FimA) protein of Porphyromonas gingivalis in oral squamous cell carcinoma.

Oral cancer is among the most common cancer in the world. Tobacco, alcohol, and viruses have been regarded as a well- known risk factors of OCC however, 15% of OSCC cases occurred each year without these known risk factors. Recently a myriad of studies has shown that bacterial infections lead to cancer. Accumulated shreds of evidence have demonstrated the role of Porphyromonas gingivalis (P. gingivalis) in OSCC. The virulence factor FimA of P. gingivalis activates the oncogenic pathways in OSCC by upregulating various cytokines. It also led to the inactivation of a tumor suppressor protein p53. The present Insilico study uses High-Throughput Virtual Screening, molecular docking, and molecular dynamics techniques to find the potential compounds against the target protein FimA. The goal of this study is to identify the anti-cancer lead compounds retrieved from natural sources that can be used to develop potent drug molecules to treat P.gingivalis-related OSCC. The anticancer natural compounds library was screened to identify the potential lead compounds. Furthermore, these lead compounds were subjected to precise docking, and based on the docking score potential lead compounds were identified. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this insilico finding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC. Workflow of Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against Fimbriae (FimA) protein of P. gingivalis in oral squamous cell carcinoma.

In-silico structural characterization and phylogenetic analysis of Nucleoside diphosphate kinase: A novel antiapoptotic protein of Porphyromonas gingivalis.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

Clinical Profile, Practice Pattern, and Outcomes With First-Line Therapy in ALK-Positive Lung Cancer: Real-World Data From Resource-Constrained Settings.

Introduction: ALK inhibitors are one of the success stories in precision medicine for treating patients with advanced ALK-positive NSCLC. Nevertheless, developing countries have substantial constraints in using ALK inhibitors, with limited data from India. Methods: An audit of a prospectively collected database of patients with advanced ALK-positive NSCLC treated from January 2013 to March 2018 was conducted. The SPSS version 20.0 was used for statistical analysis. Results: A total of 441 patients were available for analysis; 62.5% were males, median age was 50 (range: 19-75) years, and 78.3% had Eastern Cooperative Oncology Group performance status of 0 to 1. When all the lines of therapies were included in the analysis, ALK inhibitors could be used in 379 (85.9%) of the total ALK-positive patients and 292 patients (66.2%) received ALK inhibitors in the first line in any strategy. The major reason for not starting ALK inhibitors upfront was financial constraints in 69% of the patients. The median progression-free survival on first-line therapy for the entire cohort was 14.1 months (95% confidence interval [CI]: 12.2-15.9), with a significant difference between patients receiving ALK inhibitor in first line in any strategy versus not in first line (17.2 mo [95% CI: 14.5-19.9] versus 5.9 mo [95% CI: 4.2-7.6], p < 0.001). The median overall survival was 30.7 months (95% CI: 27.3-34.2), with 37.6 months (95% CI: 28.1-47.1) for ALK inhibitor in the first line versus 20.5 months (95% CI: 15.8-25.1) for subsequent lines of therapy (p < 0.001). Conclusions: Most of our patients with ALK-positive NSCLC were exposed to ALK inhibitors through various support mechanisms. Those patients who could receive ALK inhibitors in the first line had a significant survival advantage as compared with others.

Prognostic utility of microRNA-145 and CD 133 in oral squamous cell carcinoma: A pilot study from Northern India.

Introduction: Multiple factors alter the microRNAs (miRNAs) at cellular level and promote oncogenesis in oral mucosa. The present study was performed with an aim to find any expression of miRNA-145 in oral squamous cell carcinoma and correlate it with CD-133 immuno-expression, clinicopathological, and demographical variables in oral squamous cell carcinoma (OSCC) with respect to controls. Materials and methods: In a prospective observational study 50 samples from patients of OSCC and 20 from unremarkable oral mucosa were studied. After initial detailed histology, miRNA-145 profiling was performed using qRT-PCR, followed by CD-133 immunohistochemistry (IHC). Results: The mean age of patients with oral cancer was 47.5 ± 10.25 years. Mean miR-145 levels in OSCC were 0.4312 ± 0.32026 and mean in healthy controls was 0.99 ±0 .21771. There was significant downregulation of miRNA-145 in cases with respect to controls. Significant reduced levels of miRNA-145 with respect to higher clinical tumor size, pathological pT tumor, nodal status, and resultant clinical tumor stage was observed. As far as presence and absence of stem cells was concerned it was seen that tumors displaying presence of stem cells highlighted by CD-133 had lower levels of miRNA-145 as compared to tumors with absent CD-133 staining. Conclusions: miRNA-145 is significantly altered in OSCC in our patient population and its reduced values carry a poor prognosis. Its interaction with CSCs may not be significant but mean miRNA-145 levels are lower in tumors with CSCs. There should be further studies on the larger sample size for these two biomarkers, to know its value.

Epidemiological Trend of Esophageal Cancer at a Tertiary Cancer Center in Mumbai, India, Over the Past 15 Years.

BACKGROUND: In developed countries, there has been a definite change in the histopathological spectrum of esophageal cancer towards adenocarcinoma. There are limited data from India regarding the histopathological profile of patients with esophageal cancer. MATERIALS AND METHODS: We retrospectively evaluated patients with histologically proven esophageal cancer who were registered at the Tata Memorial Hospital (Mumbai, India) between 2003 and 2018. The primary aim of the study was to analyze the time-trend of the histological pattern of esophageal cancer. Our secondary objectives included evaluating whether there was any correlation between the histology of the esophageal cancer and the age, sex, socioeconomic status (the paying ability of the patient, which was reflected in the treatment category of the patient, i.e., private [full payment], general [subsidized payment], or no charge), comorbidities, and a history of substance abuse. RESULTS: Among 7874 patients with esophageal cancer, 5092 (64.7%) were men, with a male-to-female ratio of 1.8:1. The median age was 57 years (IQR, 50-65). Of the 4912 patients in whom a history of tobacco or alcohol use had been elicited, 1360 (27.7%) had no history of substance abuse. A majority of the tumors (2942, 37.4%) originated in the middle-third of the esophagus. Squamous cell carcinoma was the predominant histological type, noted in 6413 (81.4%) patients and remained the most common histologic type consistently through the study with no evidence of a time-trend in the histological pattern. On the multivariate analysis, female sex and a history of substance abuse were associated with higher odds of squamous cell carcinoma, while the presence of comorbidities and lower esophageal/gastroesophageal junction primaries were associated with higher odds of adenocarcinoma. CONCLUSIONS: There is no evidence of an epidemiological shift in the histopathologic spectrum of esophageal cancer in India over the last two decades. Four out of five Indian patients with esophageal cancer have squamous cell histology, with the commonest site of origin being the middle third. This is important to recognize, given the varying molecular spectrum and efficacy of therapeutic modalities based on histopathology.

Exploring mitigating role of zinc nanoparticles on arsenic, ammonia and temperature stress using molecular signature in fish.

BACKGROUND: The pollution and climate change in aquatic ecosystems are major problems threatening the aquatic organisms for existence in the recent timeline, which promotes the extinction of the fish species. However, the present study dealt with zinc nanoparticles (Zn-NPs) in mitigating arsenic, ammonia and high temperature stresses in Pangasianodon hypophthalmus. MATERIALS AND METHODS: To studying different gene expressions, an experiment was conducted to mitigate the multiple stressors using dietary Zn-NPs at 0, 2, 4, and 6 mg kg-1 diets. In the present investigation, the gene expressions studies were performed for growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill tissue as well as myostatin (MYST) and somatostatin (SMT) in the muscle tissue. The anti-oxidative genes CAT, SOD and GPx in liver and gill tissues were also analysed. Expression studies for stress responsive heat shock protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS), immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were performed. At the end of the experiment the fish were infected with Aeromonas hydrophila to evaluate the immunomodulatory role of Zn-NPs. RESULTS: In the present investigation, the growth hormone regulator 1 (GHR1), growth hormone regulator ß (GHRß), growth hormone (GR) in liver and gill as well as myostatin (MYST) and somatostatin (SMT) in muscle were noticeably altered, whereas, Zn-NPs at 4 mg kg-1 diet improved gene expressions. The anti-oxidant gene viz. CAT, SOD and GPx in liver and gill tissues were upregulated by stressors such as As, NH3, NH3+T. As+T and As+NH3+T. Therefore, anti-oxidant genes were noticeably improved with dietary Zn-NPs diet. The stress protein gene (HSP70), DNA damage inducible protein, inducible nitric oxide synthase (iNOS) was significantly upregulated, whereas, Zn-NPs diet was applied to the corrected gene regulation. Similarly, immune related genes such as interleukin (IL), tumour necrosis factor (TNFα), toll like receptor (TLR) and immunoglobulin were highly affected by stressors. Dietary Zn-NPs at 4 mg kg-1 diet was improved all the immune related gene expression and mitigate arsenic, ammonia and high temperature stress in fish. CONCLUSION: The present investigation revealed that Zn-NPs at 4.0 mg kg-1 diet has enormous potential to modulates arsenic, ammonia and high temperature stress, and protect against pathogenic infections in fish.

The association of long non-coding RNA in the prognosis of oral squamous cell carcinoma.

BACKGROUND: Oral cancer is considered one of the most prevalent cancers in India. This is mainly because India suffers from high usage of tobacco, which is one of the main causative agents of oral cancer, and lacks proper health and sexual hygiene in rural areas. DISCUSSION: Non-coding RNAs are reported to be involved in the various mechanism and causality of cancer. Numerous reports have identified viable prospects connecting non-coding RNA (ncRNA) with cancer. Specific ncRNAs like long non-coding RNA or lncRNAs are recently being prioritized as potential associations in the cause of cancer. CONCLUSION: This review aims at presenting a concise perspective on the basics and the recent advancements of the lncRNA research pertaining specifically to oral cancer, its recurrence, and the future possibilities of knowledge it might possess.

Porphyromonas gingivalis in oral squamous cell carcinoma: a review.

Oral cancer contributes significantly to the global cancer burden. Oral bacteria play an important role in the spread of oral cancer, according to mounting evidence. The most proven instance is the carcinogenic implications of Porphyromonas gingivalis, a key pathogen in chronic periodontitis. It is imperative to understand the pathogenesis of P. gingivalis in OSCC. This review aims to gather and assess scientific shreds of evidence on the involvement of P. gingivalis in the molecular mechanism of oral squamous cell carcinoma.

Development of one dimensional geomechanical model for a tight gas reservoir.

Estimating rock-mechanical, petrophysical properties and pre-production stress state is essential for effective reservoir planning, development, and optimal exploitation. This paper attempts to construct a comprehensive one-dimensional mechanical earth model (1D MEM) of the Mandapeta gas reservoir of Krishna Godavari (KG) basin, India. The methodology comprises a detailed stepwise process from processing and analysis of raw log data, calibration of log-derived dynamic properties with static ones using regression models developed from tested core samples, and final rock mechanical property estimation. Pore pressure profiles have been estimated and calibrated with the Repeat formation tester (RFT) data for every thirty-five wells. Overburden and horizontal stresses have also been evaluated and calibrated using data from the Leak-off Tests (LOT) or Extended Leak-off Tests (XLOT). A menu-driven program is developed using PYTHON code for visualization and on-time revision of 1D MEM. The resulting comprehensive 1D MEM predicts and establishes the rock-mechanical properties, pore pressure, and in-situ stress values of the basin. Besides its use in planning future wells, development of the field, and yielding insight into the various well challenges, it can also be used to develop a 3D MEM of the reservoir.

Utility of special drive campaign on substance use disorders in hard-to-reach communities in the fast urbanizing town of Solan, India.

AIMS: Special drive campaigns on substance use disorders (SUDs) in India are usually organized in educational institutes, non-governmental organizations, or few selected localities. Hard to reach communities of construction, prison, and industrial sites quite often remain uncovered. MATERIALS AND METHODS: During a month-long special drive in 2019, under a cross-sectional study, we reached these communities of Solan town through awareness camps and incorporated standardized screening tools for evaluating morbidity patterns of SUDs. RESULTS: Statistically significant relationship existed between 360 participants (90.8% males, 9.2% females; mean age of 33 years) and their educational levels with χ2 (1, n = 360) =130.59, P = 0.000. Fagerstrom's scale inferred very high nicotine dependence in 10.6%, 7.9%, and 2.4% of prisoners, industrial workers, and laborers, respectively. Whereas, Fagerstrom scale for smokeless tobacco revealed 31% of significant dependence potential amongst laborers. Alcohol use disorder identification test revealed 28 persons with harmful alcohol dependence. Drug abuse screening test revealed 13.6% of prisoners having moderate level drug abuse potential. The Kruskal-Wallis test showed a statistically significant difference, in levels and potential of substance use in construction, prison, and industrial sites. CONCLUSION: The study proved the utility of special drives in evaluating SUDs morbidity patterns in hard-to-reach communities.

Polymorphous adenocarcinoma of the submandibular gland.

Polymorphous adenocarcinoma (PA) of the salivary glands is a rare malignancy that predominantly affects the minor salivary glands of the palate. Major salivary gland involvement is rare (<5%). The submandibular gland is a highly unusual location for this tumour. Recently, the WHO has updated the classification of salivary gland tumours in which the PA subtype has been modified. We report a very uncommon case of a classical variant of PA involving the submandibular gland in a 49-year-old woman managed at our institute and discuss the most recent pathological criteria for diagnosis, management strategy and prognosis of PA.

Congenital Mobile Atlantoaxial Dislocation with Cervicomedullary Astrocytoma in Pediatric Patient.

Congenital mobile atlantoaxial dislocation with cervicomedullary astrocytoma has never been described. We present a case of a 7-year-old male child who presented to us with gradually progressive spastic quadriparesis following a fall from table. His lateral radiograph and magnetic resonance images showed mobile atlantoaxial dislocation with intramedullary heterogeneously enhancing cervicomedullary mass. The patient underwent suboccipital craniectomy with C1-4 laminectomy. Tumor was pinkish grey, tenacious with ill-defined plane and cyst at poles. C1-C2 fusion was done using C1 lateral mass and C2 pars screw and rod system with onlay bone graft. Histopathology revealed pilocytic astrocytoma. At the time of discharge, the patient showed improvement in spasticity. Postoperative lateral radiograph showed reduced atlantoaxial dislocation with stable construct.

Survival genes expression analysis following ionizing radiation to LiCl treated KG1a cells.

Purpose: Lithium chloride (LiCl) is clinically used for manic disorders. Its role has been shown in improving cell survival by decreasing Bax and p53 expression and increasing Bcl-2 concentration in the cell. This potential of LiCl is responsible for reducing irradiated cell death. In this study, we have explored the role of LiCl as a radioprotectant affecting survival genes.Materials and methods: To find out the cellular response upon LiCl pretreatment to radiation-exposed KG1a cells; viability, clonogenic assay and microarray studies were performed. This was followed by the detection of transcription factor binding motif in coregulated genes. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and chromatin immunoprecipitation (CHIP).Results: LiCl improved irradiated KG1a cell survival and its clonogenicity at 2 mM concentration (clinically used). Microarray data analysis showed differential expression of cell-protecting genes playing an important role in apoptosis, cell cycle, adhesion and inflammation, etc. The coregulation analysis revealed genes involved in bile acid biosynthesis were also affected by LiCl treatment, these genes are likely to be responsible for radiation-induced gastrointestinal (GI) syndrome through bile production.Conclusions: This is the first study with respect to global genetic expression upon LiCl treatment to radiation-exposed cells. Our results suggest considering repurposing of LiCl as a protective agent for radiation injury.

Postinfectious Glomerulonephritis with Crescents in an Elderly Diabetic Patient after Acute Gastroenteritis: Case Report.

Postinfectious glomerulonephritis (PIGN) is primarily a disease of childhood. It occurs after upper respiratory tract infection or skin infections. Streptococcus is the most common causative agent, but in the elderly, staphylococcus is the main culprit. In adults, PIGN is more common in immunocompromised patients, particularly diabetics and alcoholics. Here, we report the case of an elderly diabetic male who presented with severe acute kidney injury with active urinary sediment after acute gastroenteritis. Additional analyses revealed a very low serum C3 level and a normal serum C4 level. Renal biopsy showed diffuse proliferative glomerulonephritis with crescents. Direct immunofluorescence showed mesangial and capillary wall staining for C3 and IgG (2+, mesangial and segmental capillary wall, granular). Renal electron microscopy showed subepithelial hump-like electron-dense deposits. The role of steroid in the treatment of PIGN is controversial and there is no standard protocol, but our patient responded very well to steroid as he did not require hemodialysis after 2 weeks of initiation of steroid therapy. We should be aware of an atypical presentation of PIGN in elderly to ensure correct diagnosis.

Podophyllotoxin and Rutin Modulate M1 (iNOS+) Macrophages and Mitigate Lethal Radiation (LR) Induced Inflammatory Responses in Mice.

Accidental exposure to lethal doses of Gamma radiation leads to the systemic inflammatory syndrome which causes mortality. In view of this, management of hemopoietic syndrome by modulating pro-inflammatory response in clinically manageable time period seems to be the most appropriate strategy for encountering radiation induced damage and recovery. As both tissue and peripheral macrophages are critical for the management of radiation induced injuries, we have unraveled the immunomodulatory potential of radioprotective formulation (G-003M) on peripheral macrophages populations in this study. G-003M inhibited lethal radiation induced NO and Th1 effector cytokines in the exposed macrophages indicating its M1 dim polarizing capacity. In similar lines, conditioning of mice with G-003M before lethal irradiation (LR) inhibited LR induced titre of Th1 effector cytokines in both serums as well as in lung, small intestine, and spleen tissue confirming its immunomodulatory potential. G-003M potentially down modulated inflammatory response in LPS induced inflammatory model and enhanced M2 polarization of iNOS+ M1 effector macrophages providing a molecular hint on G-003M mechanism of action on macrophages. These observations revealed that G-003M potentially modulate pro-inflammatory programming of macrophages and mitigate radiation-induced inflammatory stress which is believed to contribute significantly to radioprotective attribute of G-003M. In this study, we demonstrate that Rutin and Podophyllotoxin drive M1dim/M2 polarization of LR primed macrophages apart from protecting DNA from radiation. These drugs have the capacity to programme innate immune cells like macrophages which may be involved in homeostasis during recovery.