Types Of Cancer Research Articles

Prognostic and Immunotherapeutic Role of TACC3 in Pancancer, and its Impact on Proliferation and Docetaxel Resistance in Lung Adenocarcinoma.

Transforming acidic coiled-coil containing protein 3 (TACC3) exerts a vital role in cancer progression by modulating cell division and facilitating tumor growth. Given the lack of comprehensive research on the pan-cancer implications of TACC3, our study aimed to analyze the functional role of TACC3 in pan-cancer and validate it through experimental investigations in lung adenocarcinoma. We first employed various bioinformatics techniques to investigate the expression and prognostic significance of TACC3 in pancancer. Subsequently, we analyzed the correlation between TACC3 and immune infiltration, immune checkpoints, drug sensitivity, as well as the prediction of immune therapy response. Finally, we validated the association between TACC3 and the proliferation of lung adenocarcinoma, as well as its resistance to docetaxel, through in vitro experiments. Here, TACC3 exhibited high expression in human cancers and was associated with poor prognosis in various cancer types. It was also involved in immune infiltration and demonstrated a strong predictive ability for immune therapy response. Through drug sensitivity prediction, we further identified a potential association between TACC3 and docetaxel resistance, which was subsequently validated in lung adenocarcinoma. Our investigation of TACC3 revealed its potential as a promising target both for immunosuppression and docetaxel resistance in pan-cancer, especially in lung adenocarcinoma.

The Role of Physical Activity in Cancer Survivorship: A Comprehensive Review

Cancer survivorship is an increasingly important focus in oncology, with physical activity (PA) emerging as a key intervention to enhance health outcomes post-treatment. This review explored the role of PA in improving quality of life (QoL), reducing recurrence risk, and managing treatment-related side effects among cancer survivors. The biological mechanisms of PA, including the reduction of systemic inflammation and improvement of immune function, are discussed. Additionally, the psychological and social benefits, such as reduced anxiety and social support from group-based exercise, are highlighted. Despite these benefits, numerous barriers to PA exist, including physical limitations, psychological challenges, and socioeconomic factors. Facilitators, such as tailored exercise programs and healthcare provider recommendations, can enhance participation. Special considerations, such as cancer type and age, necessitate personalized approaches to PA to maximize benefits for diverse survivor populations. The methodology involved synthesizing data from recent clinical trials, epidemiological studies, and qualitative research. In conclusion, physical activity is a vital component of survivorship care, with the potential to significantly improve both longevity and QoL. Future research should focus on refining exercise prescriptions and developing scalable interventions for widespread implementation in cancer care. Keywords: Cancer survivorship, Physical activity, Quality of life (QoL), Exercise interventions, Cancer recurrence prevention.

Understanding how CD19 expression levels impact the response to loncastuximab tesirine: a plain language summary.

In this article, we summarize results from a clinical study called LOTIS-2, in which researchers looked at patients with a type of blood cancer called diffuse large B-cell lymphoma, or DLBCL for short. Patients received the drug loncastuximab tesirine, or Lonca for short, which targets a marker on the surface of tumor cells called CD19.Patient information from the LOTIS-2 study, other studies of Lonca, and information from scientific publications was used to develop a quantitative systems pharmacology (QSP) model, which can predict how Lonca works in the body. The goal was to use the QSP model to see if CD19 levels can predict tumor size changes after Lonca treatment and if Lonca can still work to treat DLBCL when CD19 levels are very low. The prior LOTIS-1 and LOTIS-2 trials demonstrated an acceptable safety profile for Lonca, and therefore the current study did not evaluate safety data. Researchers used immunohistochemistry, a common technique to evaluate CD19 expression. They found that there was no association between patients who responded to Lonca treatment and levels of CD19 on their tumor cells. Some patients with low or even undetectable levels of CD19 on their tumor cells had observable decreases in tumor size after Lonca treatment. While Lonca uses the CD19 target to find and destroy cancer cells, Lonca does not require a large amount of CD19 to kill tumor cells. These results mean that Lonca may be an effective treatment for patients with DLBCL, even if CD19 expression in tumors is undetectable by immunohistochemistry.

Chitosan-coated nanoemulsion for intranasal administration increases temozolomide mucosal permeation, cellular uptake, and In vitro cytotoxicity in glioblastoma multiforme cells

Glioblastoma multiforme (GBM) is the most prevalent and aggressive type of brain cancer in adults. Temozolomide (TMZ) is the chemotherapeutic agent used to treat primary central nervous system tumors. However, TMZ's clinical effectiveness faces several challenges due to its physical-chemical properties and biological features of GBM, such as the blood-brain barrier (BBB). Mucoadhesive nanosystems such as those coated with chitosan represent a promising alternative for optimizing the delivery of therapeutic agents to the central nervous system, as they possess ideal characteristics that enhance their interaction with the intranasal mucosa. We aimed to develop a chitosan-coated nanoemulsion containing temozolomide (CS-NE-TMZ) for nose-to-brain delivery and characterize its physical-chemical and in vitro biological properties. CS-NE-TMZ were obtained by emulsification followed by sonication. The optimized CS-NE-TMZ presented droplet size of 123,4 ± 2,3 nm, polydispersity index of 0.273 ± 0.028, zeta potential of +21,5 ± 0,81 mV, entrapment efficiency of 100 ± 1,91 % and drug loading of 2 ± 0,007 %. An in vitro release study of CS-NE-TMZ showed sustained release for up to 24 h following the Korsmeyer-Peppas model with Fickian diffusion. CS-NE-TMZ demonstrated significantly enhanced ex vivo mucosal permeation, compared to free TMZ, and showed enhanced in vitro cellular uptake, selectively increasing cytotoxicity in U-87MG glioma cells but not in healthy L929 fibroblasts, reinforcing the potential of mucoadhesive nanoemulsions as effective intranasal drug delivery systems for future brain cancer therapies.

The state of cancer care in Russia: pancreas cancer (C25). The survival rate of patients, taking into account the stage, localization and histological structure. Part II (clinical-population study)

Pancreas cancer (С25) is a cancer with an unfavorable prognosis, remains one of the most lethal types of cancer, at the national level mortality exceeds morbidity. The analysis of patient survival at the population level on the scale of federal districts is not carried out in Russia with the exception of the North-West Federal District. Considering that the levels of standardized rates of morbidity and mortality from pancreas cancer are close in Russia and NWFD, and the value of index of accuracy practically coincide, the results of the population cancer registry (PCR) of the NWFD RF actually characterize the state of cancer care on average in Russia, with the exception of autonomous districts. The aim of the second stage of the study was to identify the true state of the effectiveness of the oncological service in Russia by calculating a key parameter – evaluating its performance, specifically, calculating the leading parameter – the survival rate of patients, taking into account the stage, localization, histological structure, and the possibility of curing patients The conducted research made it possible to determine the effectiveness of providing specialized oncological care to patients with pancreas cancer at the federal district level. An increase in the one–year observed survival rate for the period from 2000 to 2004 to 2015-2019 was established from 16.0 to 21.8% or by 36.3%, and five–year from 5.1 to 6.0%. The median survival rate did not reach 4 years. A significant difference in the levels of one-year survival of patients in different age groups has been established. Significant defects in the distribution of patients according to the stage of the disease were revealed. The specification of patient survival by detailed localization groups and major histotypes of tumors was studied.

Evidence-based medicine: Indole-3-carbinol and resveratrol in human papillomavirus-associated conditions

Of all types of cancer in the female reproductive system, cervical cancer has the greatest social significance due to its impact on young patients, often even those who have not yet completed their reproductive function, and it is the third leading cause of cancer-related death. Considering the lack of etiological therapy for human papillomavirus and associated diseases, the high demand for effective methods of medical therapeutic support, and the absence of a gold standard treatment apart from destructive and excisional methods, it seems reasonable to consider the use of nutrients with anticancer effects in the treatment of low-grade cervical intraepithelial neoplasia both as an addition to the watchful waiting strategy and in the use of ablative treatment methods, as well as their adjuvant appointment in the case of obligatory precancer. Based on domestic and foreign literature sources from electronic databases such as PubMed, CyberLeninka, and Elibrary, this review presents data on the use of trans-resveratrol and indole-3-carbinol in HPV-associated diseases. The combination of two mutually complementary anticancer antioxidants – indole-3-carbinol, which primarily has antiproliferative effects, and trans-resveratrol, which restores cellular apoptosis mechanisms, comprehensively affects the pathogenetic mechanisms of the virus-induced pathological process: it has been proven to reduce the expression of oncogenes E6 and E7, increase the expression of tumor suppressor proteins – p53, pRb, PTEN, and decrease markers of proliferation PCNA and Ki-67. The combination of 200 mg of indole-3-carbinol and 60 mg of trans-resveratrol for the prevention of persistent papillomavirus infection and the treatment of cervical intraepithelial neoplasia has impressive potential; however, further research is needed to determine the most effective application schemes.

Cancer disparities by age: a focus on sexual and gender minorities.

The purpose of this study is to examine the age at which sexual and gender minorities are diagnosed with cancer relative to heterosexual cisgender individuals. We use population-based representative Behavioral Risk Factor Surveillance Survey data with self-reported sexual orientation, gender identity, cancer diagnoses, and the age at diagnosis. We determined the mean age at diagnosis and used logistic regression modeling to obtain odds ratios, reporting significant differences defined as p < 0.05. Separately, we adjusted for race/ethnicity and corrected for underlying differences in the age of survey respondents. Compared to heterosexual cisgender populations, sexual and gender minorities are diagnosed about 4-11years earlier, with bisexual women and transgender individuals reporting the youngest age, 43.9 and 52.1years, respectively. When focusing on select cancer types, lesbian and bisexual women are diagnosed earlier with breast, melanoma, other skin cancers, and leukemia & lymphoma. Gay and bisexual men are diagnosed earlier with colorectal cancers, and transgender individuals earlier with breast, prostate, melanoma, and other skin cancers compared to heterosexual men and women. These findings suggest that sexual and gender minorities experience earlier onset of cancer and many of these age differences remained even after adjustments were made. These findings need to be confirmed in oncology settings that have cancer incidence and sexual orientation and gender identity data and call for greater attention to sexual and gender minorities in cancer research.

Flavonoids as Chemosensitizers in Leukemias.

Flavonoids, a diverse group of natural compounds abundant in plants, fruits, and seeds, are not only responsible for the vibrant colors, fragrances, and flavors found in nature but also possess significant health benefits. Representing a secondary metabolite, these phytonutrients contribute to overall well-being. They have garnered considerable interest due to their diverse biological roles, encompassing antioxidant, anti-inflammatory, and anticancer properties. Flavonoids exert anticancer properties by interfering with different signaling pathways and molecules. Also, they have been demonstrated to exert chemosensitization features, where flavonoids may enhance the effectiveness of chemotherapy, and hold promise for improving cancer treatment outcomes as they have been discovered to make cancer cells more responsive to treatment. Understanding their influence on the regulation of cellular signaling provides a foundation for exploring their potential in combination with different chemotherapy agents and their possible single use for cancer treatment. Besides, they are believed to present a cost-effective approach to cancer therapeutics with possible implications for reducing the side effects of the current chemotherapy regimens, which can be a great therapeutic strategy for treating cancer types, including leukemia. This chapter explores potential approaches for creating anticancer treatments, focusing on leukemia, through integrating flavonoid nutraceuticals with traditional chemotherapy agents.

Node-RADS: a systematic review and meta-analysis of diagnostic performance, category-wise malignancy rates, and inter-observer reliability.

To perform a systematic review and meta-analysis to estimate diagnostic performance, category-wise malignancy rates, and inter-observer reliability of Node Reporting and Data System 1.0 (Node-RADS). Five electronic databases were systematically searched for primary studies on the use of Node-RADS to report the possibility of cancer involvement of lymph nodes on CT and MRI from January 1, 2021, until April 15, 2024. The study quality was assessed by modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Quality Appraisal of Diagnostic Reliability (QAREL) tools. The diagnostic accuracy was estimated with bivariate random-effects model, while the pooled category-wise malignancy rates were obtained with random-effects model. Six Node-RADS-CT studies and three Node-RADS-MRI studies covering nine types of cancer were included. The study quality was mainly damaged by inappropriate index test and unknown timing according to QUADAS-2, and unclear blindness during the rating process according to QAREL. The area under hierarchical summary receiver operating characteristic curve (95% conventional interval) was 0.92 (0.89-0.94) for Node-RADS ≥ 3 as positive and 0.91 (0.88-0.93) for Node-RADS ≥ 4 as positive, respectively. The pooled malignancy rates (95% CIs) of Node-RADS 1 to 5 were 4% (0-10%), 31% (9-58%), 55% (34-75%), 89% (73-99%), and 100% (97-100%), respectively. The inter-observer reliability of five studies was interpreted as fair to substantial. Node-RADS presented a promising diagnostic performance with an increasing probability of malignancy along higher category. However, the evidence for inter-observer reliability of Node-RADS is insufficient, and may hinder its implementation in clinical practice for lymph node assessment. Question Node-RADS is designed for structured reporting of the possibility of cancer involvement of lymph nodes, but the evidence supporting its application has not been summarized. Findings Node-RADS presented diagnostic performance with AUC of 0.92, and malignancy rates for categories 1-5 ranged from 4% to 100%, while the inter-observer reliability was unclear. Clinical relevance Node-RADS is a useful tool for structured reporting of the possibility of cancer involvement of lymph nodes with high diagnostic performance and appropriate malignancy rate for each category, but unclear inter-observer reliability may hinder its implementation in clinical practice.

ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B

Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 – ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.

From Genomic Exploration to Personalized Treatment: Next-Generation Sequencing in Oncology

Next-generation sequencing (NGS) has revolutionized personalized oncology care by providing exceptional insights into the complex genomic landscape. NGS offers comprehensive cancer profiling, which enables clinicians and researchers to better understand the molecular basis of cancer and to tailor treatment strategies accordingly. Targeted therapies based on genomic alterations identified through NGS have shown promise in improving patient outcomes across various cancer types, circumventing resistance mechanisms and enhancing treatment efficacy. Moreover, NGS facilitates the identification of predictive biomarkers and prognostic indicators, aiding in patient stratification and personalized treatment approaches. By uncovering driver mutations and actionable alterations, NGS empowers clinicians to make informed decisions regarding treatment selection and patient management. However, the full potential of NGS in personalized oncology can only be realized through bioinformatics analyses. Bioinformatics plays a crucial role in processing raw sequencing data, identifying clinically relevant variants, and interpreting complex genomic landscapes. This comprehensive review investigates the diverse NGS techniques, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and single-cell RNA sequencing (sc-RNA-Seq), elucidating their roles in understanding the complex genomic/transcriptomic landscape of cancer. Furthermore, the review explores the integration of NGS data with bioinformatics tools to facilitate personalized oncology approaches, from understanding tumor heterogeneity to identifying driver mutations and predicting therapeutic responses. Challenges and future directions in NGS-based cancer research are also discussed, underscoring the transformative impact of these technologies on cancer diagnosis, management, and treatment strategies.

The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer

BackgroundBreast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need. We previously discovered that hyperactivating purinergic receptors (P2RXs) by increasing extracellular adenosine triphosphate (eATP) concentrations enhances TNBC cell lines’ response to chemotherapy. Heparan sulfate inhibits multiple extracellular ATPases, so it is a molecule of interest in this regard. In turn, heparanase degrades polysulfated polysaccharide heparan sulfate. Importantly, previous work suggests that breast cancer and other cancers express heparanase at high levels. Hence, as heparan sulfate can inhibit extracellular ATPases to facilitate eATP accumulation, it may intensify responses to chemotherapy. We postulated that heparanase inhibitors would exacerbate chemotherapy-induced decreases in TNBC cell viability by increasing heparan sulfate in the cellular microenvironment and hence, augmenting eATP.MethodsWe treated TNBC cell lines MDA-MB 231, Hs 578t, and MDA-MB 468 and non-tumorigenic immortal mammary epithelial MCF-10A cells with paclitaxel (cytotoxic chemotherapeutic) with or without the heparanase inhibitor OGT 2115 and/or supplemental heparan sulfate. We evaluated cell viability and the release of eATP. Also, we compared the expression of heparanase protein in cell lines and tissues by immunoblot and immunohistochemistry, respectively. In addition, we examined breast-cancer-initiating cell populations using tumorsphere formation efficiency assays on treated cells.ResultsWe found that combining heparanase inhibitor OGT 2115 with chemotherapy decreased TNBC cell viability and tumorsphere formation through increases in eATP and activation of purinergic receptors as compared to TNBC cells treated with single-agent paclitaxel.ConclusionOur data shows that by preventing heparan sulfate breakdown, heparanase inhibitors make TNBC cells more susceptible to chemotherapy by enhancing eATP concentrations.

A computational analysis of the oncogenic and anti-tumor immunity role of P4HA3 in human cancers

Prolyl-4-hydroxylase subunit alpha3 (P4HA3) is a triple helical procollagen synthesis protein. The role of P4HA3 in cancer development is not well known and lacks comprehensive analyses among human cancers. This study aimed to investigate the relationship between P4HA3 expression and anti-tumor immunity and its prognostic value in pan-cancer. P4HA3 expression was analyzed from TIMER2.0, GTEx, GEPIA2.0 and TCGA databases. Genetic and DNA methylation alterations, survival analysis and proteins co-expression analysis of P4HA3 in cBio Cancer Genomics Portal, TCGA, GSCA and TIMER2.0. The correlation between P4HA3 expression and immune infiltration was analyzed by TIDE, XCELL, MCPCOUNTER, and EPIC. We performed EdU and transwell experiments to evaluate the influence of P4HA3 on the proliferation, migration and invasion abilities of different tumors. Patients derived xenograft (PDX) and subcutaneous transplantation models were utilized to explore the correlation between P4HA3 and immunotherapy response in triple-negative breast cancer (TNBC). Among 33 types of cancers, P4HA3 had generally different expression between different tumors, further analysis showed that the expression of P4HA3 was correlated with the cells infiltration of the tumor microenvironment (TME). The expression of P4HA3 was positively with the cell proliferation markers and epithelial-mesenchymal transition (EMT) markers. Moreover, P4HA3 deficiency inhibited the proliferation, migration and invasion abilities of tumor cells, and promoted anti-tumor immunotherapy of PD-1/PD-L1 inhibitor. This pan-cancer analysis of P4HA3 provides a comprehensive understanding of its oncogenic and prognosis role in different cancers, P4HA3 abnormal expression could be a useful biomarker for predicting the effectiveness of immunotherapy in cancer patients.

Analysis of the effectiveness of primary treatment of stage IA–IIA ovarian cancer. Siberian Journal of Oncology

Aim: to determine the effectiveness of primary treatment of patients with ovarian cancer of stages IA–IIA.Material and Methods. The study included 336 (100 %) patients with histologically confrmed ovarian cancer of stages IA–IIA, who were treated at the Primorsky Regional Oncology Center from 2004 to 2021. The overall survival (s) and progression-free survival (PFS) were analyzed depending on clinical and morphological factors: histological type of cancer, BRCA1/2 mutation, profle of the clinic where surgical treatment was performed, surgical staging and chemotherapy option. The examination for a mutation in the BRCA1/2 gene was performed by a new generation sequencing method. The data were statistically processed using the IBM SPSS Statistics 26 program.Results. The average age of patients with stage IA–IIA ovarian cancer was 52.12 ± 12.13 years. Statistically signifcantly higher survival rates were in patients with histological tumor type low-grade serous carcinoma compared with high-grade serous carcinoma (S: p=0.010 and IBP: p=0.020), with surgical treatment in specialized hospitals compared with patients operated in gynecological hospitals (s: p=0.040 and IBP: p=0.020), during adequate surgical staging (OV: p=0.008 and IBP: p=0.010), during treatment with platinum and taxanes (OV: p=0.001 and IBP: p=0.001).Conclusion. It was shown that about 30 % of patients with stage IA–IIA ovarian cancer in Primorsky Krai received primary surgical treatment in non-specialized hospitals, which increased the risk of progression and death by 1.7 times. A low percentage of adequate surgical staging was noted (12.5 %). Adjuvant chemotherapy with platinum and non-oxane agents worsened the prognosis of the disease. Patients with low-grade serous carcinoma had a more favorable prognosis (by 60 %). There was no statistically signifcant effect of the presence of a mutation in the BRCA1/2 genes on survival rates.

Enhancing Cancer Treatment Through Combined Approaches: Photodynamic Therapy in Concert with Other Modalities

This review explores the role of photodynamic therapy (PDT) as an adjunctive treatment for cancers, with a focus on its potential to enhance the effects of established therapies like chemotherapy, surgery, and radiotherapy. Given the limitations of conventional cancer treatments, PDT’s ability to improve therapeutic outcomes through combination strategies is examined. In cancers such as lung, breast, cholangiocarcinoma, and cervical, PDT shows promise in enhancing response rates, reducing recurrence, and minimizing adverse effects when used alongside standard modalities. This study highlights current findings on PDT’s mechanisms in complementing chemotherapy, augmenting surgical precision, and enhancing radiotherapeutic effects, thus offering a multi-faceted approach to cancer treatment. Additionally, insights into the clinical application of PDT in these cancers emphasize its potential for reducing tumor resistance and supporting more effective, personalized care. By providing an overview of PDT’s synergistic applications across diverse cancer types, this review underscores its emerging significance in oncology as a tool to address traditional treatment limitations. Ultimately, this review aims to inform and inspire researchers and clinicians seeking to refine and innovate cancer therapy strategies through PDT integration, contributing to the advancement of more effective, synergistic cancer treatments.

Enhancing transcription–replication conflict targets ecDNA-positive cancers

Extrachromosomal DNA (ecDNA) presents a major challenge for cancer patients. ecDNA renders tumours treatment resistant by facilitating massive oncogene transcription and rapid genome evolution, contributing to poor patient survival1–7. At present, there are no ecDNA-specific treatments. Here we show that enhancing transcription–replication conflict enables targeted elimination of ecDNA-containing cancers. Stepwise analyses of ecDNA transcription reveal pervasive RNA transcription and associated single-stranded DNA, leading to excessive transcription–replication conflicts and replication stress compared with chromosomal loci. Nucleotide incorporation on ecDNA is markedly slower, and replication stress is significantly higher in ecDNA-containing tumours regardless of cancer type or oncogene cargo. pRPA2-S33, a mediator of DNA damage repair that binds single-stranded DNA, shows elevated localization on ecDNA in a transcription-dependent manner, along with increased DNA double strand breaks, and activation of the S-phase checkpoint kinase, CHK1. Genetic or pharmacological CHK1 inhibition causes extensive and preferential tumour cell death in ecDNA-containing tumours. We advance a highly selective, potent and bioavailable oral CHK1 inhibitor, BBI-2779, that preferentially kills ecDNA-containing tumour cells. In a gastric cancer model containing FGFR2 amplified on ecDNA, BBI-2779 suppresses tumour growth and prevents ecDNA-mediated acquired resistance to the pan-FGFR inhibitor infigratinib, resulting in potent and sustained tumour regression in mice. Transcription–replication conflict emerges as a target for ecDNA-directed therapy, exploiting a synthetic lethality of excess to treat cancer.

COVID-19 infection in children with blood cancer: A systematic review.

Blood cancer is the most common type of cancer and the leading cause of death by disease past infancy among children. Children with blood cancer are vulnerable population to viral infections such as coronavirus disease 2019 (COVID-19). To estimate the incidence of COVID-19 in children with blood cancer and analyse the demographic parameters, clinical characteristics and treatment outcomes in children with blood cancer with COVID-19 illness. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and searched ProQuest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature for studies on the development of COVID-19 in children with blood cancer, published from December 1, 2019 to April 30, 2023, with English language restriction. Of the 3077 papers that were identified, 155 articles were included in the systematic review (83 case report, 54 cohort and 18 case-series studies). Studies involving 1289 children with blood cancer with confirmed COVID-19 were analysed. Leukaemias (1141 cases) were the most frequent types of blood cancer observed in children who developed COVID-19, followed by non-Hodgkin's lymphomas (59 cases), Hodgkin's lymphomas (36 cases), Langerhans cell histiocytosis (7 cases), myelodysplastic syndrome (7 cases) and myeloid neoplasm (1 case). Among all 1289 blood cancer paediatric cases who transmitted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some children were documented to be admitted to the intensive care unit (ICU) (n = 175, 13.6%), intubated and placed on mechanical ventilation (MV) (n = 111, 8.6%), suffered acute respiratory distress syndrome (ARDS) (n = 144, 11.2%) or died (n = 111, 8.6%). Overall, COVID-19 in children with different types of blood cancer resulted in no or low severity of disease in 78.6% of all included cases (COVID-19 severity: asymptomatic = 238, mild = 601, or moderate = 171). Treatment for COVID-19 was not necessary in a small number of children with blood cancer (n = 94, 7.3%). Fatality in children with blood cancer with COVID-19 was reported in any of the included blood cancer categories for leukaemias (n = 99/1141, 8.7%), non-Hodgkin's lymphomas (n = 7/59, 11.9%), Hodgkin's lymphomas (n = 2/36, 5.5%), myelodysplastic syndrome (n = 1/7, 14.3%) or myeloid neoplasm (n = 1/1, 100%). Fatality rate in children with blood cancer infected with SARS-CoV-2 was the highest in patients with Hispanic ethnicity (n = 44/111, 39.6%) and COVID-19-related fatality was highest in male patients (76.5% of deceased patients). Most studies reported to alter the intensity and regimen of anticancer treatment in children with blood cancer during course of SARS-CoV-2 infection, however, many studies have reported to successfully treat COVID-19 without any changes to the anticancer treatment. Globally, leukaemias were the most prevalent and myeloid neoplasms were the least prevalent blood cancer types in children who developed SARS-CoV-2 infection. Children with blood cancer infected with SARS-CoV-2 may experience higher rates of ICU admission and mortality in comparison with the healthy pediatric populations. Mortality in children with blood cancer and infected with SARS-CoV-2 was highest in cases belonging to male gender and Hispanic ethnicity. However, children with blood cancer tend to have milder COVID-19 symptoms and are less likely to be hospitalized and have better prognosis when compared to adults. Continuation of anticancer treatment in individual paediatric blood cancer patients with COVID-19 seems to be possible.

Bilateral Pterygium in a Paediatric Cancer Patient taking Vemurafenib: A Case Report

Introduction: Anticancer drugs with reactive oxygen species (ROS) inducing mechanisms, such as vemurafenib, have been shown to be effective against various types of cancer. However, the adverse effects of increased oxidative stress have the potential to damage not only cancer cells, but also normal cells such as those in eyes and potentially leading to ocular diseases including pterygium and cataract. Presentations: A nine-year-old patient presented with bilateral nasal pterygium and early bilateral cortical cataracts, which are uncommon for his age group. Patient has a background of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E positive pilocytic astrocytoma with anaplastic features, diagnosed at age 2.5 years old. Vemurafenib was commenced at the time of diagnosis. Conclusion: We suspect that these ophthalmic findings are associated with his prolonged treatment with vemurafenib which may be of a pathophysiological significance.

In vitro pharmacological evaluation of Methanolic leaf extract of Calotropis procera for antifungal and anti-breast cancer activities.

Medicinal plants remained the primary choice worldwide from several centuries due to many therapeutic effects in the management of infectious and non-infectious diseases. Therefore, exploration of new medicinalplants as a green medicine has the major concern of many research groups. Microbial infections and different types of cancers in human are among the common health problems both in developing as well as in developed countries. Medicinal plants as a source of anti-microbial and anti-cancer agents are still in their initial stage in modern medicine. So current research work was planned to explore the anti-fungal and anticancer potential of Calotropis procera. C. procera leaves were collected from local area of Faisalabad, Pakistan, and phytochemical, anti-microbial, and anti-cancer activities were studied following reference methods. In vitro anti-microbial study of methanolic extracts of C. procera leaves against different strains of fungal was performed. Results showed that plant extract in a dose of 5 mg/mL have significant (P<0.05) antifungal activity. Moreover, the methanolic leaf extract of C. procera displayed strong anti-cancer activity in breast cancer cells (MCF-7), with a cytotoxic activityat 200μg/mL comparable to that found for Taxol as standard drug. Findings of current research work showed that the leaf extracts of C. procera has strong potential as an antibacterial, antifungal and anti-cancer agent. However, characterization and purification of phytochemicals is required to develop drug from natural resources.

Measurable morphological features of single circulating tumor cells in selected solid tumors-A pilot study.

Liquid biopsies developed into a range of sensitive technologies aiming to analyze for example, circulating tumor cells (CTCs) in peripheral blood, which significantly deepens understanding of the metastatic process. Nevertheless, examination of CTCs is mostly limited to their enumeration and usually only 2-3 markers-based phenotyping, not offering yet sufficient insight into their biology. In contrast, quantitative analysis of their morphological details might extend our knowledge about dissemination and even improve CTC isolation or label-free identification methods dependent on their physical features such as size, and deformability. Current study was conducted to describe CTCs' and their size, shape, presence of protrusions, and micronuclei across various types of cancers (lung, n = 29; ovarian, n = 24, breast, n = 54; and prostate, n = 33). Epithelial (pan-keratins), mesenchymal (vimentin), and two exclusion markers were used to identify CTCs and classify them into four epithelial and epithelial-mesenchymal transition-related phenotypes using standardized and throughput method, imaging flow cytometry. The morphological characteristics of CTCs, including their nuclei, such as circularity, the maximum, and minimum diagonal values were determined using an open-source software QuPath. On average, detected CTCs (n = 1156) were larger, and more irregular in shape compared to leukocytes/endothelial cells (n = 400). Epithelial and mesenchymal CTCs had the largest (median = 18.2 μm) and the smallest diameter (median = 10.4 μm), respectively. In terms of cancer-specific variations, the largest CTCs were identified in lung cancer, whereas the smallest-in prostate and breast cancers. Epithelial CTCs and those negative for both epithelial and mesenchymal markers exhibited the highest degree of elongation, whereas mesenchymal CTCs were the most irregular in shape. Protrusions and micronuclei were observed extremely rarely within CTCs of breast and prostate cancer (0.6%-0.8% of CTCs). Micronuclei were observed only in epithelial and epithelial-mesenchymal CTCs. This study underscores the significant variability in the morphological features of CTCs in relation to their phenotypic classification or even the particular organ of origin, potentially influencing for example, size-dependent CTC isolation methods. It demonstrates for the first time the morphological measurements of CTCs undergoing epithelial-mesenchymal transition, and some specific morphological details (i.e., protrusions, micronuclei) within CTCs in general.