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Background Breast Cancer (BC) patients who do not obtain pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Recent evidence suggests that chemotherapy (CT) efficacy relies on the capacity of chemotherapeutic agents to interact with the immune system. BC features a unique tumor microenvironment (TME) comprising of multiple immune cell types including Macrophages that share a double-edged relationship with cancer as they get polarised from M1 (anti-tumour) to M2 (Pro-tumour). Pro-tumour M2 macrophages are referred to as tumor-associated macrophages (TAMs) and are implicated extensively in angiogenesis, metastasis and therapy resistance. Establishing role of TAMs, facilitates the emergence of novel strategies that exploit them as theranostic targets/tools of interest for treating cancer. Utility of using Drugs like Zoledronic Acid, Trabectedin, Rebastinib in combination with 5-fu have shown promising anti-TAM activity and improved response to CT in clinical trials. In this study, we have characterized presence of M2-TAM and its correlation to NACT response in matched primary and residual tumours by examining expression of several biomarkers. Methods Treatment naïve primary and their matched residual tumour specimens from 45 women treated at a single center were accessed through IERB approved protocols. The study included locally advanced HR+HER2-ve and TNBC tumours treated with standard NACT regimes between 2018 to 2020. To determine the association of TAM population with response to NACT, expression levels of CD68 (pan macrophage marker) & CD163 (marker of М2 macrophages), were detected by immunohistochemistry (IHC) and represented as combined H score. We also performed gene expression of chemokines, inflammatory cytokines and interleukins involved in M1-M2 polarization by q-RT-PCR. Residual Cancer Burden Scoring was used to assess response and patients were divided into three groups (complete responders, partial responders and non-responders). Univariate and multi variate analysis were performed between gene expression groups and IHC groups with clinicopathological parameters. Findings from this study was validated on public data bases like TCGA, METABRIC and GEO. Results: 20% of all patients included in the study were complete responders. We arrived at a Macrophage Polarisation Score (MPS) by Gene expression and also a combined H score by IHC. MPS and H-score had a positive correlation (p=0.083) overall. Interestingly, Combined analysis of H-Score and MPS with response to treatment showed a greater and statistically significant correlation with residual tumours as compared to treatment naïve tumours (p=0.009). We also observed that high MPS and high combined H score in residual tumours were associated with increased tumour size and LVI (p=0.055 and p=0.03). Other clinicopathological parameters like receptor status, grade and stage at diagnosis were not significantly associated with H score or MPS. Taken together we found that 11% of patients who exhibited high TAM score by both H sascore and MPS fell into the non-responders category. We therefore report TAMs in residual tumours being more indicative for response to therapy compared to primary tumours. Conclusion Although primary tumours are useful for building predictive models to therapy response, we have demonstrated that there is utility in examining residual tumours as well for choice to adjuvant chemotherapy, since the tumour is constantly evolving through the NACT period. More work to arrive at a “TAM score” that could aid in choice of additional adjuvant treatment strategies is underway. We believe our work is helping us to move one step closer to Precision Medicine in a low and middle income country like India that has a higher burden of locally advanced disease. Our analysis also lends itself to becoming a clinical test since it is performed on an FFPE specimen Citation Format: Lohita Krishna, Aruna Korlimarla, B S Srinath, Anugnya Ranjolkar, Sudipta Nascar, Hari PS, Durga Devi, Nidhi l, Rekha V Kumar. Tumour associated macrophages in Breast Cancer - Are they critical players in response to Neo Adjuvant Chemotherapy? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-10.

Purpose Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. Methods We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. Results Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. Conclusion Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.

Introduction and Aim: The Biosynthesis of Gold nanoparticles (Au NPs) is an eco-friendly, cost effective and nontoxic alternative to chemical and physical methods. In the present study synthesis of Au NPs was performed by using a fungi Penicillium sp. isolated from agriculture soil. Materials and Methods: Fungi was isolated from the agricultural field and inoculated into Sabouraud Dextrose broth and incubated at 28º C in a shaker at 180 rpm for 96 to 120 hours. After incubation, the fungal culture was filtered and centrifuged, obtained fungal cell free extracts treated with 1mM gold salt (HAuCl4). The synthesis of Au NPs was confirmed by UV–visible spectroscopy and particles size was measured using Dynamic Light Scattering (DLS). Haemolytic assay of Au NPs was carried out using Chicken RBCs and results measured at 540 nm in UV-visible spectrophotometer. To study catalytic activity, Bromothymol blue (BB) was subjected to reduction by using sodium borohydride (NaBH4, 5.28X10-2 M) in the presence of Au NPs. Then the color change was monitored by visual observation. Results: The synthesis of Au NPs was preliminary observed by a color change from yellow to purple and confirmed by a peak at 560 nm using a UV–visible spectroscopy. The DLS analysis showed that the Au NPs were poly-dispersed and size ranges from 130 to 150 nm. The biosynthesised Au NPs was studied for their biocompatibility and dye degradation properties. Conclusion: The obtained results revealed that biosynthesized Au NPs shows a minimum level of toxicity to chicken erythrocytes and good catalytic activity towards the degradation of hazardous dye bromothymol blue. These nanoparticles could be potentially useful in various applications in medical and environmental fields.

Purpose Gut microbiota are able to generate metabolites that can alter the function of immune cells and play a major role in health and disease. Understanding the changes in gut microbiome during infections including virus may help to use novel strategies in the therapeutic interventions. Methods We have reviewed recent reports on role of gut microbiome in lung infections and its possible importance in COVID-19. Results Most of the studies provide an insight into the possible role of gut microbes during lung diseases including chronic obstructive pulmonary disease (COPD), cystic fibrosis, lung cancer, and other respiratory problems such as allergy and asthma. However, clinical evidence underlying gut-lung crosstalk during respiratory viral infections is limited. Conclusion This review provides an overview of the role of the gut microbiome during respiratory viral infections mainly focused on COVID-19 and possible evidence for its crosstalk targeting as new therapeutics.

Purpose: To understand the role played by the immediate family in treatment decision and support in patients diagnosed with breast cancer, the influence of demographic factors on psychosocial roles of women within the family. Methods: A mixed method design used for data collection on family support, financial arrangement and psychosocial impact of cancer from 378 women with breast cancer recruited at first diagnosis between 2008 and 2012, during multiple counseling sessions. The median follow-up is 7 years with only 2% lost to follow-up. Results: Most patients (99%) had support from family members. 57% of patients met the costs of treatment through personal savings and health insurance. The rest (43%) had difficulty and had to resort to desperate measures such as selling their property or taking on high-interest personal loans. Patients with higher education and urban settings had better financial management. A male member of the family (husband or son) was the main decision maker in half of the cases. Concerns over women's responsibilities within the family varied by the age of the patient. The vast majority of women (90%) experienced social embarrassment in dealing with the disease and its aftermath. Conclusion: In India, it is the family that provides crucial support to a woman with breast cancer during her ordeal with the disease and its treatment. This study has implications on the psychosocial support beyond the cancer patients alone, to include the immediate family and consider aspects of finance and social adjustments as critical in addition to the routine medical aspects of the disease.

Vanillin and its derivative, (4-((

Vanillin and its derivative, (4-((E)-(4-hydroxy-2-methylphenylimino) methyl)-2-methoxyphenol (MMP) were showed clear inhibition of violacein and pyocyanin at sub-MICs indicating a possible quorum quenching effect of both the compounds. MMP was able to inhibit the biofilm formation in Pseudomonas aeruginosa PAO1 at 125 μg/mL (p < 0.05), while vanillin at 250 μg/mL (p < 0.05) indicating that they act against quorum sensing regulated biofilm formation. The inhibition of biofilm was confirmed by visualization through fluorescence microscopy followed by docking analysis of molecules against quorum sensing activator proteins. Caenorhabditis elegans survival assay revealed that vanillin and MMP were able to increase survival of C. elegans from P. aeruginosa PAO1 infection. The study showed that the potent features of the MMP and vanillin in inhibiting the quorum sensing regulated virulence and biofilm, which was proved in C. elegans infection model as well as molecular docking studies.

Biosynthesis of gold nanoparticles (GNPs) is an eco-friendly, cost effective and nontoxic alternative to chemical and physical methods. The microbe which inhabits nearly all surfaces on the earth, an attainment typically attributed to their metabolic adaptability. The organism which resides in gold mines would be having more capability to resist against soluble gold toxicity and produce gold nanoparticles efficiently. In the present study, we report for the synthesis of GNPs by a member of Bacillus subtilis isolated from Hutti gold mine, India. The synthesis of GNPs was observed by a color change from yellow to pink and confirmed by a peak around 545 nm using a UV–visible spectroscopy. The synthesized GNPs were further characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Transmission electron microscopy (TEM). The results show that synthesized GNPs are well dispersed and their size ranges 20–25 nm. The present work is aimed to use green synthesized GNPs as catalyst to degrade Methylene blue (MB) and these GNPs could be used to degrade toxic dyes in the environment.

In the present study, phytochemicals-mediated rapid, stable and eco-friendly synthesis of gold nanoparticles (GNPs) using Pterocarpus santalinus L. (Red Sanders) bark extract is reported. The powerful characteristics of different phytochemicals present in P. santalinus L. bark prompted us to determine their efficacy in the bio-reduction of gold chloride trihydrate to the corresponding GNPs. The biosynthesis of GNPs was investigated at the physiological condition (pH = 7.4). The synthesized GNPs were characterized by UV–visible spectroscopy by measuring the peak in the range of 400–700 nm. The GNPs synthesized at physiological conditions revealed surface plasmon resonance (SPR) at 545 nm. The crystalline nature of GNPs was confirmed by using x-ray diffraction (XRD), and the functional groups adhered on the surface of the GNPs were analyzed by Fourier Transform Infrared spectroscopy (FTIR). Transmission Electron Microscopy (TEM) analysis showed spherical GNPs in the size range of 13–26 nm. The synth...

Nanoparticles of different sizes and shapes can be synthesized by physical and chemical methods. But these methods involve toxic ingredients and hazardous byproducts which may be potentially harmful to either environment or human health. Therefore in the present study, an eco-friendly simple biosynthetic route was used for the synthesis of gold nanoparticles (GNPs) using cell free extracts of Enterobacter aerogenes. The synthesis of GNPs was preliminary observed by color change and confirmed by a peak at 530–560 nm using a UV–visible spectroscopy. The crystalline nature of the GNPs was confirmed by X-ray diffraction. TEM image showed the size of GNPs in the range of 4–6 nm. The functional groups adhered on the surface of the GNPs was analyzed by FTIR. The variation of size, shape and dispersity with the varying gold salt concentration was studied. The synthesized GNPs exhibited good catalytic activity for the reduction of methylene blue by NaBH4.

The biosynthesis of nanoparticles is a cost effective, eco-friendly and non toxic alternative to physical and chemical methods. In the present study, we report a rapid and eco-friendly method for extracellular biosynthesis of gold nanoparticles (GNPs) using cell free extract of Staphylococcus epidermidis. In this method, the formation of GNPs is rapid as the reaction process completes within few minutes. The synthesis of GNPs was preliminary observed by colour change from pale yellow to pink red and confirmed by peaks at 545–550 nm using a UV–visible spectroscopy. Transmission electron microscopy (TEM) showed formation of well dispersed GNPs in the range of 20–25 nm. Fourier transform-infrared spectroscopy (FT-IR) was used to characterise the functional groups which might have played an important role in reduction and stabilisation of GNPs. The synthesised GNPs showed good catalytic activity for methylene blue degradation. This is the first to report on the rapid and ecofriendly method for the biosynthesis of GNPs by S. epidermidis.

e11012 Background: Patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) for locally advanced breast cancer have favorable disease-free survival rates. In th...

The development of eco-friendly approach for the preparation of monodispersed gold nanoparticles (GNPs) has received much attention for their easy application. Most of the current methods involve known protocols which employ toxic chemicals and hazardous byproducts. This greatly limits their use in biomedical fields, particularly in clinical applications. Recent research has been focused on green synthesis methods to produce different nanoparticles with suitable commercial viability. The biosynthesis of monodispersed GNPs using the spent cultures of Klebsiella pneumoniae as reducing and stabilizing agent has been reported. The gold salt concentration to improve monodispersity and stability of GNPs has been optimized. Synthesized GNPs were characterized by UV–Visible spectroscopy showed absorption spectra in the range of 530–560 nm at different concentrations of HAuCl4. At the optimum reaction concentration of 1.5 mM HAuCl4, absorption peak was obtained at 535 nm. The GNPs have been further characterized by X-ray diffraction, FTIR, DLS and TEM analysis. The DLS graph showed that the particles were more monodispersed. The TEM image showed the formation of spherical shaped GNPs in the range of 4–10 nm. The effect of gold salt concentration on dispersity, size and stability of the biosynthesized GNPs has been reported.

Acute necrotising colitis and perforation of the colon due to amebic infection is usually fatal. Only three patients in the present series of nine survived surgery. Preoperative diagnosis was not possible and because of an extremely friable, blotting paper like colon, this condition was only suspected at laparotomy. Examination of ulcer scrapings for the presence of Entamoeba histolytica or histopathology is confirmatory. Resection anastomosis is mandatory as less extensive local procedures or bypass surgery are not always feasible.

Introduction and Aim: Biosynthesis of metal nanoparticles is an important branch of nanobiotechnology. In recent years, microbial biosynthesis of nanoparticles is gaining importance due to its simplicity and eco-friendliness. Materials and Methods: In this study, Selenium nanoparticles (Se NPs) were synthesized by using the fungi Fusarium sp. isolated from agricultural soil. Mycosynthesized Se NPs were characterized by UV-Vis spectrometer and Dynamic Light Scattering (DLS) analysis. Further biosynthesized Se NPs screened for different biological activities such as antibacterial, antioxidant, hemolysis, cytotoxicity and catalytic activity. Results: Synthesis Se NPs was preliminary observed by a color change from pale yellow to orange red color and confirmed by UV peak at 342 nm. The DLS result shows the particles size ranges from 19 to 43 nm.The obtained result showed that the synthesized Se NPs possess good antibacterial activity against human pathogens such as E. coli, Staphylococcus aureus, Salmonella typhi and Klebsiella pneumonia. Further biogenic Se NPs showed less cytotoxicity on yeast cells and slight hemolysis. Conclusion: The synthesized Se NPs have good antioxidant property and antibacterial activity with less haemolytic property these properties lead to use of Se NPs in different biomedical applications. This Se NPs Also showed an efficient catalytic activity by degrading hazardous dyes such as methylene blue and bromothymol blue.