Cancer Intervention Research Articles

T staging esophageal tumors with x rays.

With histopathology results typically taking several days, the ability to stage tumors during interventions could provide a step change in various cancer interventions. X-ray technology has advanced significantly in recent years with the introduction of phase-based imaging methods. These have been adapted for use in standard labs rather than specialized facilities such as synchrotrons, and approaches that enable fast 3D scans with conventional x-ray sources have been developed. This opens the possibility to produce 3D images with enhanced soft tissue contrast at a level of detail comparable to histopathology, in times sufficiently short to be compatible with use during surgical interventions. In this paper we discuss the application of one such approach to human esophagi obtained from esophagectomy interventions. We demonstrate that the image quality is sufficiently high to enable tumor staging based on the x-ray datasets alone. Alongside detection of involved margins with potentially life-saving implications, staging tumors intra-operatively has the potential to change patient pathways, facilitating optimization of therapeutic interventions during the procedure itself. Besides a prospective intra-operative use, the availability of high-quality 3D images of entire esophageal tumors can support histopathological characterization, from enabling "right slice first time" approaches to understanding the histopathology in the full 3D context of the surrounding tumor environment.

In vitro cytotoxicity assessment of biosynthesized nanoceria against MCF-7 breast cancer cell lines

Breast cancer poses a significant health concern due to its increasing prevalence and mortality rates. Hence, prompt action is needed to develop innovative therapeutic interventions, as conventional treatments exhibit severe adverse effects and have limited efficacy. This study aims to develop an innovative therapeutic intervention for breast cancer using biosynthesized nanoceria. Nanoceria has gained significant importance in the medicinal field due to its biocompatibility, dual capabilities as both antioxidant and prooxidant, and specific cytotoxicity towards cancer cells. Herein, nanoceria was biosynthesized using Echinochloa frumentaceae grain extract (EFNC) due to its eco-friendly and cost-efficient nature, and it was systematically investigated using standard characterization techniques. Furthermore, their anticancer efficacy against MCF-7 breast cancer cell lines was studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cell viability assay, and the occurrence of apoptosis was determined using acridine orange/ethidium bromide (AO/EtBr) staining. Significantly, EFNC exhibited superior anticancer efficacy even at lower concentrations (10 µg/mL), and the IC50 value was found at 47.32 µg/mL. In addition, the observed bright green and orange-red fluorescence, along with fragmented/condensed chromatin features in AO/EtBr staining clearly indicated that the EFNC caused cell death through the apoptotic route. One potential factor contributing to the observed anticancer effectiveness of EFNC could be its prooxidant properties within cancer cells. These properties ultimately enhanced oxidative stress, induced the accumulation of reactive oxygen species (ROS), and led to apoptosis. Hence, the in vitro analysis substantiated the significant anticancer efficacy of EFNC, suggesting its potential utility as a promising therapeutic agent in anticancer treatment. These findings pave the way for further exploration and development of EFNC as a valuable candidate for addressing cancer-related challenges.

An Exploratory Assessment of Pre-Treatment Inflammatory Profiles in Gastric Cancer Patients.

Gastric cancer ranks as the fifth most common cancer, and the assessment of inflammatory biomarkers in these patients holds significant promise in predicting prognosis. Therefore, data from patients undergoing surgical intervention for gastric cancer over a 7-year period were analyzed. This study was retrospective and involved a preoperative investigation of six inflammatory parameters derived from complete blood counts. Statistical analysis revealed a significant increase in the leucocyte-to-monocyte ratio (LMR) (p = 0.048), along with a significant decrease in the number of lymphocytes and monocytes compared to patients with successful discharge. Taking into consideration patients undergoing emergency surgery, a significant increase in the LMR (p = 0.009), neutrophil-to-lymphocyte ratio (NLR) (p = 0.004), Aggregate Index of Systemic Inflammation (AISI) (p = 0.01), and Systemic Immune-Inflammation Index (SII) (p = 0.028) was observed. Regarding relapse, these patients exhibited significant increases in AISI (p = 0.032) and SII (p = 0.047). Inflammatory biomarkers represent a valuable tool in evaluating and predicting the prognosis of patients with gastric cancer.

Unlocking ferroptosis in prostate cancer - the road to novel therapies and imaging markers.

Ferroptosis is a distinct form of regulated cell death that is predominantly driven by the build-up of intracellular iron and lipid peroxides. Ferroptosis suppression is widely accepted to contribute to the pathogenesis of several tumours including prostate cancer. Results from some studies reported that prostate cancer cells can be highly susceptible to ferroptosis inducers, providing potential for an interesting new avenue of therapeutic intervention for advanced prostate cancer. In this Perspective, we describe novel molecular underpinnings and metabolic drivers of ferroptosis, analyse the functions and mechanisms of ferroptosis in tumours, and highlight prostate cancer-specific susceptibilities to ferroptosis by connecting ferroptosis pathways to the distinctive metabolic reprogramming of prostate cancer cells. Leveraging these novel mechanistic insights could provide innovative therapeutic opportunities in which ferroptosis induction augments the efficacy of currently available prostate cancer treatment regimens, pending the elimination of major bottlenecks for the clinical translation of these treatment combinations, such as the development of clinical-grade inhibitors of the anti-ferroptotic enzymes as well as non-invasive biomarkers of ferroptosis. These biomarkers could be exploited for diagnostic imaging and treatment decision-making.

Nano-flow cytometry unveils mitochondrial permeability transition process and multi-pathway cell death induction for cancer therapy

Mitochondrial permeability transition (mPT)-mediated mitochondrial dysfunction plays a pivotal role in various human diseases. However, the intricate details of its mechanisms and the sequence of events remain elusive, primarily due to the interference caused by Bax/Bak-induced mitochondrial outer membrane permeabilization (MOMP). To address these, we have developed a methodology that utilizes nano-flow cytometry (nFCM) to quantitatively analyze the opening of mitochondrial permeability transition pore (mPTP), dissipation of mitochondrial membrane potential (Δ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Delta$$\\end{document}Ψm), release of cytochrome c (Cyt c), and other molecular alternations of isolated mitochondria in response to mPT induction at the single-mitochondrion level. It was identified that betulinic acid (BetA) and antimycin A can directly induce mitochondrial dysfunction through mPT-mediated mechanisms, while cisplatin and staurosporine cannot. In addition, the nFCM analysis also revealed that BetA primarily induces mPTP opening through a reduction in Bcl-2 and Bcl-xL protein levels, along with an elevation in ROS content. Employing dose and time-dependent strategies of BetA, for the first time, we experimentally verified the sequential occurrence of mPTP opening and Δ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\Delta$$\\end{document}Ψm depolarization prior to the release of Cyt c during mPT-mediated mitochondrial dysfunction. Notably, our study uncovers a simultaneous release of cell-death-associated factors, including Cyt c, AIF, PNPT1, and mtDNA during mPT, implying the initiation of multiple cell death pathways. Intriguingly, BetA induces caspase-independent cell death, even in the absence of Bax/Bak, thereby overcoming drug resistance. The presented findings offer new insights into mPT-mediated mitochondrial dysfunction using nFCM, emphasizing the potential for targeting such dysfunction in innovative cancer therapies and interventions.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis

BackgroundOver years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. ObjectiveOur study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. MethodsResearchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. ResultsFollowing screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. ConclusionThe NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Recent advances in lung cancer research: unravelling the future of treatment.

Lung cancer, a multifaceted disease, demands tailored therapeutic approaches due to its diverse subtypes and stages. This comprehensive review explores the intricate landscape of lung cancer research, delving into recent breakthroughs and their implications for diagnosis, therapy, and prevention. Genomic profiling and biomarker identification have ushered in the era of personalised medicine, enabling targeted therapies that minimise harm to healthy tissues while effectively combating cancer cells. The relationship between pulmonary tuberculosis and lung cancer is examined, shedding light on potential mechanisms linking these two conditions. Early detection methods, notably low-dose computed tomography scans, have significantly improved patient outcomes, emphasising the importance of timely interventions. There has been a growing interest in segmentectomy as a surgical intervention for early-stage lung cancer in recent years. Immunotherapy has emerged as a transformative approach, harnessing the body's immune system to recognise and eliminate cancer cells. Combining immunotherapy with traditional treatments, such as chemotherapy and targeted therapies, has shown enhanced efficacy, addressing the disease's heterogeneity and overcoming drug resistance. Precision medicine, guided by genomic profiling, has enabled the development of targeted therapies like tyrosine kinase inhibitors, offering personalised treatments tailored to individual patients. Challenges such as drug resistance and limited accessibility to advanced therapies persist, emphasising the need for collaborative efforts and innovative technologies like artificial intelligence. Despite challenges, ongoing interdisciplinary collaborations and technological advancements offer hope for a future where lung cancer is treatable and preventable, reducing the burden on patients and healthcare systems worldwide.

Abstract LB020: Extracellular vesicle-mediated intrinsic induction of ferroptosis causes reversal of chemoresistance in lung cancer

Abstract Introduction: Resistance to chemotherapeutic drugs is the major cause of treatment failures and high mortality in lung cancer(LC). Thus, strategies to overcome chemoresistance is the major thrust area of cancer research. Ciplatin (CDDP) is the first line of chemotherapeutic interventions in lung cancer however, the treatment benefit diminishes due to develop resistance against the drug. Dysregulation of apoptosis is the major reason for developing chemoresistance. Ferroptosis is a recently discovered form of non-apoptotic regulated cell death (RCD) that can overcome the apoptosis mediated resistance. To exploit this our laboratory has developed a novel Extracellular Vesicle (EV)-iron oxide nanoparticle (IONP) hybrid system- 'ExoFeR,' that can induce ferroptosis. Experiments conducted on LC cells and patient derived tumoroids (PDTs) have shown reversal of CDDP resistance after ExoFeR treatment. Our study demonstrates the utility of ferroptosis as alternate treatment intervention for treating chemoresistant LC tumors. Materials and methods: EVs derived from normal lung fibroblast cells (MRC9) were loaded with IONPs. The complex was characterized by Transmission electron microscopy (TEM), Inductively coupled plasma mass spectrometry (ICP-MS) and through Zeta potential measurements. The induction ferroptosis by ExoFeR was confirmed in Non-Small Cell Lung Cancer (NSCLC) A549 cells and NSCLC PDTs by Prussian blue, FerroOrange, and Mito-FerroGreen staining. Further, ferroptosis markers like GPX4 and SCL7A11/xCT were evaluated to examine the induction of ferroptosis. Finally, A549 cells and resistant NSCLC PDTs were tested for sensitivity to chemo drugs. Results: Physicochemical characterization indicated the successful formulation of ExoFeR. Reduction in the expression level of SLC7A11/xCT- and GPX4 proteins in ExoFeR-treated NSCLC cells and PDTs suggested induction of ferroptosis which also showed sensitization of chemo drug (cisplatin). Summary/Conclusion: We report here the synthesis of a novel EV-IONP-based system that can intrinsically induce ferroptosis and overcome chemoresistance by circumventing the conventional apoptosis-based resistance. Our finding is expected to develop a potent cancer treatment strategy for efficiently treating resistant NSCLC tumors. Citation Format: Akhil Srivastava, Anjugam Paramananantham, Rahmat Asfiya. Extracellular vesicle-mediated intrinsic induction of ferroptosis causes reversal of chemoresistance in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB020.

Abstract LB187: Investigating the roles of ROR1/2 in non-small cell lung carcinoma NSCLC and potential therapeutic applications

Abstract Lung cancer is the leading cause of cancer mortality worldwide, representing an unmet medical need. Receptor tyrosine kinase-like orphan receptors (RORs) are oncofetal antigens that act as receptors/co-receptors of WNT5A and other related noncanonical WNT proteins, in transducing β-catenin independent WNT signaling. Dysregulated ROR/WNT have been linked to cancer progression and therapy resistance. Recently, ROR receptors have drawn increasing attention as anti-cancer targets of antibody-drug conjugates (ADCs) due to their selective expression on the tumor cell surface. The ROR family contains ROR1 and ROR2, which share 58% sequence homology. However, their functional interactions between ROR/WNT5A and whether RORs have distinct or redundant roles in tumor phenotypes remain unclear. In this study, we sought to address these biological questions in NSCLC, and investigate the potential application of anti-ROR therapies. To this end, we used CRISPR/Cas9 to generate clones of ROR1 or ROR2 single knockouts (KOs) in the NSCLC LCLC-103H cell line and implemented an array of assays to characterize the effect of single ROR KOs. ROR KOs were confirmed by both western blot and flow cytometry. We found reduced ROR2 mean fluorescence intensity (MFI) on ROR1 KOs and increased ROR1 MFI on ROR2 KOs in flow cytometrical analysis. Phenotypically, ROR1 KOs did not affect tumor doubling time, but ROR2 KOs promoted cell proliferation in 2D cultures. Unlike 2D cultures, tumor 3D spheroid proliferation was significantly inhibited in both ROR1 and ROR2 KOs, implying that each ROR is indispensable in maintaining tumor growth featured by cell-cell/extracellular matrix interactions. Mechanistically, ROR1 KOs tended to decrease ROR2 and WNT5A/B protein expression, while ROR2 KOs caused compensatory upregulation of ROR1 and WNT5A/B. Both ROR1 and ROR2 KOs decreased SNAIL expression, which is a key driver of epithelial-to-mesenchymal plasticity (EMP). Furthermore, alterations in ROR1/2 signaling pathways were observed. We have identified pathways downstream of ROR1/2 including WNT, EMP, and survival, which may shed light on the biological roles of RORs in cancer and potential therapeutic intervention. Finally, the therapeutic application of ROR1/2 was evaluated by monomethyl auristatin F (MMAF) containing anti-ROR ADCs. ROR1 KOs demonstrated the on-target cytotoxicity of anti-ROR1 ADC, while ROR2 KOs showed increased sensitivity to anti-ROR1 ADC due to the increased ROR1 expression in ROR2 KOs. In vivo analysis is currently underway. Collectively, our results demonstrate that RORs have both distinct and compensatory functions in regulating tumor proliferation. We believe a greater understanding in ROR1/2 biology may lead to better targeted therapeutic applications. Citation Format: Wen-An Pan, Xin Guo, Christina Galang, Mira Ko, Jeff Kucharski, Nicole Miller, Haim Moskowitz, Jeff Watkins, Brian Lannutti, Katti Jessen, Hao Liu. Investigating the roles of ROR1/2 in non-small cell lung carcinoma NSCLC and potential therapeutic applications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB187.

Abstract LB004: Deciphering oncogenic dedifferentiation: A proteomic approach to quantifying stemness scores and unveiling druggable targets

Abstract Cancer progression and therapeutic resistance are closely linked to the acquisition of a stemness phenotype. In this context, we introduce a novel protein expression-based stemness index (PROTsi) designed to evaluate oncogenic dedifferentiation in relation to histopathology, molecular features, and clinical outcomes in tumor samples. The methodology involved the application of a machine learning model to predict the stemness molecular phenotype, leveraging proteomic data. The prediction model was built from human pluripotent stem cells from the Human Induced Pluripotent Stem Cells Consortium (HipSci). Using datasets sourced from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) across eleven distinct tumor types, we validate PROTsi's effectiveness in accurately quantifying stem-like features. Integrating the PROTsi with gene expression, DNA methylation, microRNA expression, copy number alteration, and protein post-translational modification data such as protein acetylation, glycosylation, and phosphorylation, we unveiled proteogenomic associations related to stemness. This comprehensive analysis enabled the identification of proteins and modified proteins functioning as active nodes within transcriptional networks, thereby steering the cancer aggressiveness. Proteins highly correlated with stemness were identified as potential drug targets both tumor-specific and shared among tumor types. The stemness-associated proteins we identified demonstrate prognostic value for clinical outcomes, as confirmed through immunohistochemistry in independent samples. This underscores PROTsi's efficacy as a valuable tool for selecting both prognostic protein and drug targets. This dual functionality enhances its utility in customizing anti-cancer therapy and propels the clinical development of effective cures for diverse cancer patient populations. In conclusion, our study not only introduces PROTsi as a robust method for evaluating stemness in cancer but also sheds light on potential opportunities for targeted therapies, emphasizing the significance of personalized treatment strategies in the pursuit of more effective cancer interventions. Citation Format: Iga Kołodziejczak-Guglas, Renan Simões, Elizabeth G. Demicco, Rossana L. Segura, Alexander J. Lazar, Weiping Ma, Erik Storrs, Francesca Petralia, Antonio Colaprico, Felipe da Leprevost, Pietro Pugliese, Michele Ceccarelli, Alexey I. Nesvizhski, Bożena Kamińska, Bing Zhang, Henry Rodriguez, Mehdi Mesri, Ana I. Robles, Clinical Proteomic Tumor Analysis Consortium, Li Ding, Tathiane M. Malta, Maciej Wiznerowicz. Deciphering oncogenic dedifferentiation: A proteomic approach to quantifying stemness scores and unveiling druggable targets [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB004.

Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation

The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2. Here we show the pivotal role of the reciprocal regulation between RAP2 GTPase and the cytoskeleton in Hippo signaling. RAP2 deletion undermines the responses of the Hippo pathway to external cues tied to RhoA GTPase inhibition and actin cytoskeleton remodeling, such as energy stress and serum deprivation. Notably, RhoA inhibitors and actin disruptors fail to activate LATS1/2 effectively in RAP2-deficient cells. RNA sequencing highlighted differential regulation of both actin and microtubule networks by RAP2 gene deletion. Consistently, Taxol, a microtubule-stabilizing agent, was less effective in activating LATS1/2 and inhibiting cell growth in RAP2 and MAP4K4/6/7 knockout cells. In summary, our findings position RAP2 as a central integrator of cytoskeletal signals for Hippo signaling, which offers new avenues for understanding Hippo regulation and therapeutic interventions in Hippo-impaired cancers.

IJCM_156A: A Cross-sectional study on the Prevalence of Risk Factors of Breast Cancer and Awareness of Breast Cancer Screening in Women of age group 30 to 70 years in Karamadai Block of Coimbatore Health Unit District

Background: Breast cancer, the most common malignancy among women globally, recorded over 2.26 million new cases and almost 685,000 deaths in the same year. Evidence indicates breast cancer risk links to both modifiable and non-modifiable lifestyle factors. Promoting education and access to screening programs is crucial for early detection and intervention in breast cancer. This approach ultimately enhances the effectiveness of prevention efforts and reduces complications and mortality of breast cancer. Objective: To estimate the prevalence of risk factors of breast cancer and to assess the awareness of breast cancer screening in women of age group 30-70 years in Karamadai Block of Coimbatore Health Unit District. Methodology: A cross sectional study was conducted among 150 women in Coimbatore using a semi-structured questionnaire and statistical analysis was done using SPSS 21 version. Results: Out of 150 participants, the mean age of subjects was 50 ± 11 years, with 98% being married women. The prevalence of modifiable and non- modifiable risk factors of breast cancer were found to be 61% and 9% respectively. 54% were aware of government facility-based breast cancer screening. But only 25% had undergone screening for breast cancer. Individuals who underwent breast cancer screening in the last one year found to be aware of breast cancer screening compared to those who did not. (OR 2.5, 95% CI 2.02-3.18). Conclusion: Awareness and screening for breast cancer are low among the study participants. Women =30 years of age attending all outpatient departments in any health facility should be educated regarding the importance of screening of breast cancer.

Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

Intervensi Spiritual untuk Meningkatkan Kesejahteraan Spiritual Pasien Kanker

This study aimed to explore and synthesize the scientific literature on the types of spiritual interventions that are effective in improving spiritual wellbeing in cancer patients. The method used was a systematic review through the PubMed, Science Direct, EBSCOhost and Springer Link databases using the keywords: cancer patients OR oncology patients OR patients with cancer AND spiritual interventions AND spiritual well being OR spiritual health OR spiritual healing, with inclusion criteria for cancer patients aged >18 years, January 2010 - September 2023 the selection process used the PRISMA method and the quality assessment of articles using the JBI tools RCT design. The number of initial search articles was 6725 articles with 13 articles used. The results showed that 8 spiritual interventions were found to be statistically effective in improving the mean spiritual well-being score in cancer patients. Conclusion spiritual interventions can be effective in improving spiritual well-being in cancer patients who have metastases and are in palliative care as well as those with chemotherapy. Keywords: Spiritual Interventions, Cancer Patients, Spiritual Well-Being

Roles of reactive oxygen species in inflammation and cancer.

Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.

Anticancer Activity of the Thai Herbal Formula “Kerra” Versus Afatinib and Doxorubicin In Vitro

One of the greatest challenges impeding the achievement of global health goals and afflicting millions of people each year is cancer. Prevailing cancer treatment options come with inherent risks, and significant adverse effects, and can result in financial burdens. Nowadays, many turn to alternative medicine, which have played an integral part in the treatment of a myriad of diseases especially when other approaches are ineffective or unable to be deployed. However, an opulent number of herbs seldom have reliable evidence derived from research to support their claims of phytochemical properties contributing to the alleviation of illnesses. Kerra is a Thai herbal formula that possesses immunomodulatory properties and anti-tumor activities which provides a safe, efficacious, and holistic treatment for cancer. Kerra offers therapeutic benefits without resulting in severe adverse effects, ameliorates overall welfare and quality of life for advanced care patients, and is cost-effective, allowing them to be vastly accessible for widespread use, particularly in areas facing disparities due to insufficient economic stability. This study explores the in vitro anticancer effect of the Kerra formula utilizing cytotoxicity assays on six cancer cell lines, compared to afatinib, a targeted therapy for non-small cell lung carcinoma, and doxorubicin, a chemotherapeutic agent. Anticancer activity was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and the half-maximal inhibitory concentrations (IC50) were calculated for the A431, A549, HepG2, HCT-116, NCI-H1975, MCF-7, and HeLa cell lines. Kerra showed the best effectiveness against HCT-116 and A431. The IC50 values showing inhibition of the growth of colorectal carcinoma (HCT-116 cell line) by Kerra, afatinib, and doxorubicin are 72.96, 3.574, and 63.39 µg/ml, respectively. The IC50 values for inhibition of epidermoid carcinoma (A431 cell line) by Kerra and afatinib are 96.1 and 2.449 µg/ml, respectively. The findings revealed the Kerra extract can inhibit the growth of different types of cancer cells. From our results, Kerra may be advantageous to use in conjunction with conventional cancer interventions, offer an economical solution, and improve the quality of life remarkably for end-stage cancer patients by mitigating severe adverse events.

Baseline breast tissue characteristics determine the effect of tamoxifen on mammographic density change.

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.

Portable Detection of Lysine Acetyltransferase Activity in Lung Cancer Cells Based on a Miniature Electrochemical Sensor.

The detection of lysine acetyltransferases is crucial for diagnosing and treating lung cancer, highlighting the necessity for highly efficient detection methods. We developed a portable, highly accurate, and sensitive technique using fast-scan cyclic voltammetry (FSCV) to determine the activity of the lysine acetyltransferase TIP60, employing a novel miniature electrochemical sensor. This approach involves a compact electrochemical cell, merely 3 mm in diameter, that holds solutions up to 50 μL, equipped with a conductive indium tin oxide working electrode. Uniquely, this system operates on a two-electrode model compatible with the FSCV, obviating the traditional requirement for a reference electrode. The system detects TIP60 activity through the continuous generation of CoA molecules that engage in reactions with Cu(II), thereby significantly improving the accuracy of the acetylation analysis. Remarkably, the detection limit achieved for TIP60 is notably low at 3.3 pg/mL (S/N = 3). The results show that the reversible dynamic acetylation can be effectively regulated by inhibitor incubation and glucose stimulation. This cutting-edge strategy enhances the analysis of a broad spectrum of biomarkers by modifying the responsive unit, and its miniaturization and portability significantly amplify its applicability in biomedical research, promising it to be a versatile tool for early diagnostic and therapeutic interventions in lung cancer.

Cancer patterns in Arua district, Uganda: a hospital-based retrospective study.

Cancer is the second leading cause of mortality with over 19 million cases and 10 million deaths worldwide. Available data on cancer patterns in Uganda are through modelling of data from two population-based cancer registries (PBCRs) representing only about 10% of the cancer situation in Uganda. This study sought to determine the common types of cancer among adults and children in Arua District over a 5-year period (2017-2021). Retrospective cohort chart review and 'catchment population approach' were employed. All newly diagnosed cancer patients from Arua between 2017 and 2021 were included in this study. Data were collected using Redcap whereas management and analysis were conducted using Stata 17. Cancer patterns were computed as frequencies and percentages and the interest was in finding out the common cancers among adults (above 19 years) and children (0-19 years). Over the 5-year study period, a total of 1,118 new cancer cases were registered, with slightly more females (52.1%). The top five common cancers irrespective of sex and age were: liver cancer (13.7%), cervical (11.8%), breast (10.7%), oesophagus (10.5%) and Burkitt's lymphoma (BL) (6.4%). In this study, 15.3% (n = 171) of the study participants were children. The top five common childhood cancers included BL (42%), leukemia (10.5%), other lymphomas (9.4%), osteosarcoma (4.7%) and nephroblastoma (3%). There is a high incidence of liver cancer in Arua district. The high levels of cervical, breast and oesophagus cancer were consistent with what is reported by the two PBCRs in Uganda. However, BL could be due to the presence of a BL treatment centre at Kuluva hospital in Arua. Cancer interventions in Arua should therefore be targeted towards liver, cervix, breast, and oesophagus cancer and furthering research on the reason for the high incidence of liver cancer.

USP7 interacts with and destabilizes oncoprotein SET

Oncoprotein SE translocation (SET) is frequently overexpressed in different types of tumors and correlated with poor prognosis of cancer patients. Targeting SET has been considered a promising strategy for cancer intervention. However, the mechanisms by which SET is regulated under cellular conditions are largely unknown. Here, by performing a tandem affinity purification-mass spectrometry (TAP-MS), we identify that the ubiquitin-specific protease 7 (USP7) forms a stable protein complex with SET in cancer cells. Further analyses reveal that the acidic domain of SET directly binds USP7 while both catalytic domain and ubiquitin-like (UBL) domains of USP7 are required for SET binding. Knockdown of USP7 has no effect on the mRNA level of SET. However, we surprisingly find that USP7 depletion leads to a dramatic elevation of SET protein levels, suggesting that USP7 plays a key role in destabilizing oncoprotein SET, possibly through an indirect mechanism. To our knowledge, our data report the first deubiquitinase (DUB) that physically associates with oncoprotein SET and imply an unexpected regulatory effect of USP7 on SET stability.