Reactive oxygen species of tumor microenvironment: Harnessing for immunogenic cell death.

The tumor microenvironment (TME) is a dynamic and complex system that undergoes continuous changes in its network architecture, notably affecting redox homeostasis. These alterations collectively shape a diverse ecosystem actively supporting tumor progression by influencing the cellular and molecular components of the TME. Despite the remarkable clinical advancements in cancer immunotherapy, its spectrum of clinical utility is limited by the altered TME and inadequate tumor immunogenicity. Recent studies have revealed that some conventional and targeted therapy strategies can augment the efficacy of immunotherapy even in patients with less immunogenic solid tumors. These strategies provoke immunogenic cell death (ICD) through the ROS-dependent liberation of damage-associated molecular patterns (DAMPs). These DAMPs recognize and bind with Pattern Recognition Receptors (PRRs) on immune cells, activating and maturing defense cells, ultimately leading to a robust antitumor immune response. The present review underscores the pivotal role of redox homeostasis in orchestrating the transition of TME from a cold to a hot phenotype and the ROS-ICD axis in immune response induction. Additionally, it provides up-to-date insights into strategies that leverage ROS generation to induce ICD. The comprehensive analysis aims to develop ROS-based effective cancer immunotherapies for less immunogenic tumors.

Small molecular inhibitors: Therapeutic strategies for pancreatic cancer.

Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively. However, despite the US FDA approving over 100 small-molecule targeted antitumor drugs, challenges such as low response rates and drug resistance persist. This review delves into the possibility of using small molecules to treat persistent or spreading PC, highlighting the challenges and the urgent need for a diverse selection of inhibitors to develop more effective treatment strategies.

Deciphering the potential of proteomic-based biomarkers in women's reproductive diseases: empowering precision medicine in gynecology.

CONTEXT: Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. OBJECTIVE: This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. CONCLUSION: We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.

Treatment patterns and long-term survival outcomes for patients with stage III non-small cell lung cancer: A retrospective study.

AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.

Enhancing wheat crop production with eco-friendly chitosan encapsulated nickel oxide nanocomposites: A safe and sustainable solution for higher yield.

In this work, we looked at using nickel oxide (NiO) nanocomposites with chitosan encapsulation as a nano-primer to improve wheat crop output. A straightforward green precipitation procedure was used to create the nanocomposites, and they were then characterized using several methods. According to the findings, the chitosan-encapsulated NiO nanocomposites possessed a large surface area and were resilient to changes in pH. Following this, wheat seeds were primed with the nanocomposites, and under greenhouse circumstances, the impact on crop growth was assessed. The findings demonstrated that, in comparison to the control group, nanocomposites priming considerably enhanced wheat growth and germination rate up to 99 %. In comparison to untreated plants, the wheat plants treated with the nanocomposites primer had greater plant height i.e. shoot length (11.4 cm) and root length (10.3 cm), leaf area, and biomass accumulation. Further research into the mechanism underlying the priming effect of nanocomposites on wheat growth revealed that the nanocomposites enhanced nutrient absorption, photosynthesis, and stress tolerance in wheat plants. In conclusion, our research shows that chitosan-encapsulated NiO nanocomposites have the potential to improve wheat crop productivity in an environmentally benign and long-term manner, offering a viable strategy for sustainable farming.

Removal of organic and inorganic effluents from wastewater by using degradation and adsorption properties of transition metal-doped nickel ferrite.

Removal of water pollutants (methylene blue dye and heavy metals) was achieved by zinc/manganese-doped nickel ferrites (Ni1 - xMxFe2O4, where x = 0.00, 0.025, 0.10). Degradation of dye was achieved under natural solar light illumination. Degradation studies of dye were conducted under different parameters such as contact time-80 min, dye's concentration-5 mg/L, pH-7, and dosage of ferrites-15 mg. The adsorption of dye was studied using non-linear kinetics models (pseudo-first-order and pseudo-second-order) and isotherm models (Langmuir and Freundlich). The adsorption of dye followed pseudo-first-order kinetics (R2 = 0.99377) than second-order kinetics (R2 = 0.98063) and Langmuir isotherm model (R2 = 0.96095) than Freundlich model (R2 = 0.95962) with maximum adsorption efficiency of 29.62 mg/g. Doping of nickel ferrites caused an increase in the removal percentage of methylene blue dye (80 to 90%) and inorganic effluents (75 to 95% for lead and 47 to 82% for cadmium). In addition to this, band gap energy (2.43 to 3.26 eV) (UV-Vis spectroscopy), pore radius (65.2 to 74.8 A°), and specific surface area (16.45 to 27.95 m2/g) (BET analysis) were also increased. Generally, the results of the study revealed that synthesized nanoparticles can act as potential candidate for the removal of effluents from wastewater under optimum parameters along with recyclability, reusability, and separation under the influence of a magnetic field.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice.

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.

A literature review on correlation between HPV coinfection with C. trachomatis and cervical neoplasia - coinfection mediated cellular transformation.

Cervical cancer is the fourth most common cause of mortality worldwide. Persistent infection with high-risk human papillomaviruses (hrHPV) is a known significant risk factor in cervical neoplasia development (CN). Though HPV contributes to carcinogenesis, other factors provide an ideal niche for persistence of HPV, especially, coinfection with Chlamydia trachomatis (CT) which has been linked to CN development. CT infection is associated with inflammation, cell proliferation, EMT transition and anti-apoptotic processes. To better understand the correlation between HPV-CT coinfection and CN development, a literature review was conducted on the prevalence of HPV-CT coinfection focusing on the role of infection-induced inflammation as HPV-CT coinfection creates an environment for cellular transformation, activates an innate immune response and triggers EMT transition. Moreover, inflammation plays a crucial role in developing neoplasia as there is a decrease in effector cells and a change in the levels of players like ROS and miRs. CT infection induces chronic inflammation followed by cervical epithelial cell damage and increases susceptibility to HPV infection which may lead to cellular transformation. The literature search was performed based on a comprehensive investigation of publications in the PubMed journal database and Scopus, on the development of CN. We have reviewed the prevalence of HPV-CT infection and the factors increasing the risk of developing CN.

Microbiome Assisted Tumor Microenvironment: Emerging Target of Breast Cancer.

The microbiome assisted tumor microenvironment (TME) supports the tumors by modulating multiple mechanisms. Recent studies reported that microbiome dysbiosis is the main culprit of immune suppressive phenotypes of TME. Further, it has been documented that immune suppressive stimulate metastatic phenotype in TME via modulating signaling pathways, cell differentiation, and innate immune response. This review aims at providing comprehensive developments in microbiome and breast TME interface. The combination of microbiome and breast cancer, breast TME and microbiome or microbial dysbiosis, microbiome and risk of breast cancer, microbiome and phytochemicals or anticancer drugs were as used keywords to retrieve literature from PubMed, Google scholar, Scopus, Web of Science from 2015 onwards. Based on the literature, we presented the impact of TME assisted microbiome dysbiosis and estrobolome in breast cancer risk, drug resistance, and antitumor immunity. We have discussed the influence of antibiotics on the breast microbiome. we also presented the possible dietary phytochemicals that target microbiome dysbiosis to restore the tumor suppression immune environment in breast TME. We presented the microbiome as a possible marker for breast cancer diagnosis. This study will help in the identification of microbiome as a novel target and diagnostic markers and phytochemicals and microbiome metabolites for breast cancer treatment.

Association of cervicovaginal dysbiosis mediated HPV infection with cervical intraepithelial neoplasia.

Cellular transformation to malignancy is a multifactorial process strongly linked with microbiome dysbiosis. The female reproductive tract (FRT) is inhabited by specific Lactobacillus spp which play a significant role in maintaining a homeostatic balance and providing resistance to perturbation. Any imbalance in the resident microbiota of the FRT results in cervicovaginal dysbiosis and increased predisposition to viral and bacterial infections. In the present review, we discuss the critical role played by the cervicovaginal microbiome in maintaining cervicovaginal homeostasis. Loss of the mutualistic relationship between cervicovaginal microbiota and the host leads to increased susceptibility to Human papilloma virus (HPV) infection. HPV in coinfection with Chlamydia trachomatis has been linked with increased risk for cellular transformation. The progression to cervical neoplasia is a multistep process regulated by cellular and epigenetic changes mediated by oncogenes and miRNA. Exosomes derived from the infected cells play an important role in the pathological development and progression to cervical neoplasia as they harbor the regulatory molecules like miRNA, proteins and prooncogenic factors which may facilitate cellular transformation.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.

Severe infusion reaction due to nivolumab: A case report.

BACKGROUND: Nivolumab is an anti-PD1 immune checkpoint inhibitor commonly used for the treatment of solid organ and hematological malignancies. Severe infusion reaction due to nivolumab is quite rare. CASE: We report a case of severe infusion reaction due to nivolumab necessitating ICU admission and withdrawal of further nivolumab use in a patient with metastatic non-small cell lung cancer. CONCLUSION: Our knowledge and expertise with the use of immune checkpoint inhibitors are still evolving. This report highlights one of the rare possible side-effects that clinicians and patients may have to face with increasing indications and use of nivolumab in day to day practice.

Nanotheranostics: Their role in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy worldwide. Despite advances in imaging techniques, early diagnosis and management remain very poor. The early diagnosis of HCC requires diagnostic and imaging technologies with high sensitivity and precise quantification ability and with no tissue penetration limit. Nanotechnology-based cancer imaging is a rapidly emerging research area with significant applications in the diagnosis and treatment of cancer, which we review here with application to HCC. Furthermore, we discuss the combination of functional nanotheranostics and magnetic resonance imaging (MRI) for targeted delivery of phytochemical therapeutics, chemotherapeutic drugs, RNAi-based therapeutics, and vaccinations. Finally, this review presents the importance of MRI biomarkers for monitoring HCC treatment response. The use of advanced nanotheranostics as MRI contrast agents for imaging, diagnosis and drug delivery may enhance HCC management and provide a new area of research in tumor imaging technology.

Resection of colorectal cancer liver metastases in older patients.

BACKGROUND: Colorectal cancer remains a common cancer in the western world, with liver resection being the only potentially curative option for isolated colorectal cancer liver metastases (CRCLM). Cancer is a disease of aging, with the optimum management of elderly patients with CRCLM presenting an ongoing dilemma. METHODS: We analysed the outcome of CRCLM using prospectively collected patient data from the multidisciplinary Treatment of Recurrent and Advanced Colorectal Cancer registry, collected from July 2009 to July 2018 at 12 Australian hospitals. RESULTS: Of 2742 patients with metastatic colorectal cancer, liver-limited disease was present in 977 (36%) patients, of whom 338 (35%) underwent hepatic resection. Resection rates varied with age, including 186 (43%) of 428 patients aged 64 years and younger, 99 (40%) of 245 aged 65-75 years and 53 (17%) of 303 aged 76 and older (P < 0.001). The 30-day mortality rate was 0.9%. Median survival post resection also varied with age, 96 versus 89 versus 68 months (P < 0.001). In a separate analysis of the oldest patients, those aged over 80 years, where only 11% underwent resection, the median survival was 49 months. CONCLUSION: The operative mortality for patients undergoing liver resection at Australian hospitals is low. With advancing age, the rate of liver resection of CRCLM and the post-resection survival decline. However, excellent survival outcomes can be achieved in selected elderly patients.

A comparative anticancer study on procyanidin C1 against receptor positive and receptor negative breast cancer.

Albezia odoratissima has many health benefits. The present study investigated the isolation, characterization and anticancer activity of procyanidin C1 from A. odoratissima bark. Procyanidin C1 was isolated and characterized by IR, 13C NMR, 1H NMR and LC-MS spectroscopic studies. Anticancer property of procyanidin C1 was explored by studying the expression of checkpoint kinases, Bcl-2 and BAX, cell cycle, DNA damage and caspase 3 and 9 levels. Procyanidin C1 exhibited significant cytotoxicity against TNBC (MDA-MB- 231), hormone positive (MCF-7) cell lines. Its IC50 value is comparable to tamoxifen towards MDA-MB- 231 cell line, but considerably higher towards MCF-7 cell line. Procyanidin C1 induced DNA damage, cell cycle arrest and enhanced the expression of checkpoint kinases. Procyanidin C1 decreased the level of Bcl-2 but increased the BAX, caspase 3 and 9 expression in cancer cells. This study indicates the antiproliferative property of procyanidin C1 against breast cancer cells by inducing apoptosis.

Recent advances in metabolomics of triple negative breast cancer.

Triple-negative Breast Cancer (TNBC) is considered as the most aggressive subtype of breast cancer. Metabolic profiling has a great significance in cancer research due to profound changes in the metabolism of cancer cells. It has been used to investigate the entire set of metabolites and changes associated with it in disease conditions. These changes in the expression levels of metabolites bring functional changes associated with the pharmacological or nutritional intervention. The present minireview presents a brief note on changes associated with TNBC aggressiveness in terms of metabolomics.

Marine natural compound cyclo(L-leucyl-L-prolyl) peptide inhibits migration of triple negative breast cancer cells by disrupting interaction of CD151 and EGFR signaling.

Cyclo (L-Leucyl-L-Prolyl) peptide/CLP is a marine natural metabolite and well recognized as an antimicrobial and antioxidant agent with limited studies on anticancer activity. The current study aims to determine the effect of CLP on migration and growth of triple negative breast cancer cell lines. The anti-growth potential was evaluated by MTT, BrdU and TUNEL assays; DNA damage by γH2AX and Dead green assays; antimigration activity by Boyden chamber invasion and wound healing assays. Interaction of CLP with CD151 was resolved by PatchDock. Effect of CLP on the expression of transmembrane CD151 was evaluated by cell-based ELISA assay. The interaction between CD151 and EGFR was predicted by using FireDoc Web server. Impact of CLP on the interaction of CD151 with EGFR was evaluated by co-immunoprecipitation assay. The effect of CLP on the cell cycle and its controlling proteins was determined by Western blotting. CLP reduced the viability of MDA-MB-231 and MDA-MB-468 TNBC cell lines but not human breast healthy epithelial cell line (MCF-12A) similar to eribulin, standard. CLP also inhibited proliferation; cell cycle and migration. It induced DNA strand breaks, DNA damage, and cell death. It showed the most favorable interactions with CD151 in in silico docking and significantly reduced the expression of membrane-bound CD151 proteins. FireDoc Web study predicted the association between CD151 and EGFR with -29.13 kcal/mol of binding energy. CLP reduced the interaction of CD151 with EGFR along with the expression of cyclin D, CDK4, PAK, RAC1, and P27kiP1. This study concludes that CLP suppresses growth and migration by attenuating cell cycle of TNBC cell lines via EGFR and CD151 signaling. Thus, exploring the EGFR and CD151 signaling pathway targeted by CLP may provide a new approach in the treatment of TNBC.

Cytogenetic, Molecular, and Translational Applications in Pancreatic Ductal Adenocarcinoma: Current Evidence and Future Concepts.

Pancreatic cancer or pancreatic ductal carcinoma is one of the most destructive human malignancies; it is frequently diagnosed at advanced and incurable metastatic stages. In contempt of the voluminous research in the recent past, it became resistant to currently existing, clinically approved therapeutic regimens. Recent advances in cytogenetic, molecular, and translational applications for understanding the pathophysiological and molecular mechanisms of this disease have opened up new avenues for novel therapeutic strategies. In this review, we present current literature on the cytogenetic, molecular, and translational applications in pancreatic ductal carcinoma, and we emphasize current evidence and future concepts for the development of novel diagnostic and therapeutic approaches and their clinical implications.

Effect of MMP-2 gene silencing on radiation-induced DNA damage in human normal dermal fibroblasts and breast cancer cells.

INTRODUCTION: Diagnostic and therapeutic ionizing radiation (IR) is one of the well known long term risk factors of breast cancer. Extremely lethal consequences of IR causes double-strand breaks, which are mainly responsible for genomic instability, altered gene expression, and cell death. FINDINGS: This study evaluated the effect of matrix metalloproteinases-2 (MMP-2) gene silencing using MMP-2 shRNA expression plasmids (pMMP-2) on IR induced cytotoxicity and DNA damage by MTT, dead green, γH2AX and comet assays in human normal dermal fibroblasts (HDFs) and MCF-7 human breast cancer cells. IR has decreased the viability of HDFs and MCF-7 cells with increasing IR (2-10Gy). IR induced DNA damage in both HDFs and MCF-7 cells. However, pMMP-2 transfection has increased the viability of irradiated HDFs (10Gy) and significantly decreased the viability of irradiated MCF-7 cells (10Gy). Further, DNA damage in terms of γH2AX foci decreased with pMMP-2 transfection in irradiated HDFs (10Gy) and increased in irradiated MCF-7 cells (10Gy). In addition, MMP-2 gene silencing using pMMP-2 decreased comet tail length in irradiated HDFs but increased in irradiated MCF-7 cells. CONCLUSIONS: The results conclude that pMMP-2 has protected HDFs and sensitized the MCF-7 cells from IR induced DNA damage. This differential response might be due to IR induced MMP-2 distinctive ROS generation in HDFs and MCF-7 cells.

Synergistic enhancement of apoptosis by coralyne and paclitaxel in combination on MDA-MB-231 a triple-negative breast cancer cell line.

Triple-negative breast cancer (TNBC) is the most outrageous subtype of breast cancer. Emphasizing the urge of new approach in cancer therapy, combinational drug therapy may be proven as an effective strategy. In our previous study, we reported that coralyne (COR) with paclitaxel (PTX) efficiently decreases the proliferation of MDA-MB-231 compared with MCF-7 cell line. Thus, we studied the effect of COR and PTX in combination on apoptosis of MDA-MB-231 cell line. In silico results demonstrated that COR intercalates DNA at a minor groove. In vitro approaches revealed that in combination (COR and PTX) increases the efficacy of apoptosis in MDA-MB-231 cell line by a significant increase in G1/S phase arrest, DNA fragmentation, and change in mitochondria membrane potential. The expression of ATM and ATR a serine/threonine-protein kinase, ataxia telangiectasia and Rad3-related protein were depleted with an increase in time from 24 to 48 hours in concurrent with increased levels of γH2AX indicating that DNA damage routes cells to enter apoptosis. This was confirmed by high levels of caspase-3 and cytochrome c. Also, the decrease in the expression levels of matrix metalloproteinase-9 confirmed the antimetastatic efficacy of COR + PTX. The present study indicates that the synergistic effect of COR and PTX can enhance apoptosis in MDA-MB-231 cell line and may be proven as a potential anticancer therapy against TNBC.