Malignant Tumors Research Articles

Asparaginase and isoaspartyl peptidase 1 RNA interference suppresses the growth of nasopharyngeal carcinoma cells

Nasopharyngeal carcinoma (NPC) is one of the common malignant tumors, and its pathogenesis has not been fully clarified. This study aims to explore the impact of RNA interference on the growth and invasion of NPC cells. Asparaginase and isoaspartyl peptidase 1 (ASRGL1)-short hairpin(sh) RNA expressing lentivirus was used to investigate the effect of ASRGL1 knockdown on NPC cells (C666-1 and SUN-1). The target shASRGL1 gene was determined by mRNA and protein expression in nasopharyngeal carcinoma cells; nasopharyngeal carcinoma cell proliferation viability, migration, invasion, apoptosis, ATP levels, and oxidative stress were examined. The results found that ASRGL1 was found to be highly expressed in NPC tissues and cell lines. shASRGL1 exhibited a high gene expression knockdown efficiency, downregulated the ASRGL1 protein expression in the nasopharyngeal carcinoma cells, suppressed proliferation viability of transfected nasopharyngeal carcinoma cells, inhibited their migration and invasion and ATP levels, promoted nasopharyngeal carcinoma cell apoptosis, ROS, and ferroptosis. shASRGL1 plays a role in protecting against NPC cell growth and invasion.

GelMA microneedle-loaded bio-derived nanovaccine shows therapeutic potential for gliomas

ABSTRACT Glioma is the most common primary malignant tumor of the central nervous system in adults. Although immunotherapy, especially tumor vaccines, has made some progress in the treatment of gliomas compared with surgery and radiotherapy. However, the lack of specific or relevant tumor antigens severely limits the further development of tumor vaccines. Here, we report a bio-derived vaccine (TMV@CpG) derived from glioma cell membrane vesicles and carrying TLR9 agonist CpG as adjuvant, which was loaded onto the GelMA microneedle to obtain the microneedle vaccine (MN-TMV@CpG). Microneedle vaccine fully utilize the innate immune cells rich in the skin, inducing stronger cellular immune responses. In subcutaneous tumor models, MN-TMV@CpG reversed the immune-suppressing microenvironment of tumor, and effectively inhibited tumor progression. In an intracranial tumor model, MN-TMV@CpG significantly prolonged the survival duration and induced stronger immune memory responses in tumor bearing mice when combined with anti-PD1 mAb. These results suggest that bio-derived nanovaccines can be used as a potential antitumor immunotherapy strategy.

Pediatric Bone Tumors: Location and Age Distribution of 420 Cases

Background/Objectives: One of the most important diagnostic tools in bone tumors is X-rays. Preliminary and, in the case of some benign lesions, definitive diagnoses are formed using this basic tool. Part of the decision making in this stage is based on statistical probability using the patient’s age, as well as the incidence and predilection sites of different entities. The information used today is based on older and fragmented data. To verify the underlying principles, we retrospectively evaluated all bone tumors in children and adolescents treated by our tertiary center in the last 20 years. Methods: For this retrospective study, patients under the age of 18 years suffering from histopathologically verified bone tumors were evaluated. Data were retrieved from our local musculoskeletal tumor database. Results: We were able to include 420 children treated for bone tumors in our tertiary center. The cohort consisted of 335 benign and 85 malignant lesions. The most common lesions were 137 osteochondromas; the malignant tumors consisted mainly of osteosarcomas (53) and Ewing’s sarcomas (28). The primary predilection sites were the metaphyses of long bones. Conclusions: We were able to confirm and supplement the fragmentary data of these rare diseases using our own cohort.

ETS1 promotes cisplatin resistance of NSCLC cells by promoting GRP78 transcription.

Non-small cell lung cancer (NSCLC) is a common malignant tumor characterized by rapid growth and invasive power. Glucose regulatory protein 78 (GRP78) is important in cancer cell progression. Here, this study aimed to explore the effect and mechanism of GRP78 on cisplatin (DDP) resistance of NSCLC cells. qRT-PCR and Western blot detected the expression of genes and proteins. Flow cytometry was used to analyze endoplasmic reticulum stress (ERS) induced by DDP in NSCLC. Cell proliferation and apoptosis were examined using cell counting kit-8 (CCK8), cell cloning, and flow cytometry, respectively. Chromatin immunoprecipitation assay (CHIP) and dual-luciferase reporter assays were performed to determine the binding of ETS1 and GRP78 promoter. Mouse xenograft models were constructed for in vivo analysis. ERS was induced by DDP in NSCLC cells. GRP78 were upregulated in DDP-resistant NSCLC tissues, and knockdown of GRP78 suppressed DDP resistance, clone formation, promoted apoptosis, and inhibited ERS in DDP-resistant NSCLC cells. ETS1 knockdown repressed GRP78 expression and NSCLC tumor growth. Interestingly, ETS1 played a role in DDP-resistant NSCLC via GRP78. ETS1 inhibits cisplatin sensitivity of NSCLC cells by promoting GRP78 transcription.

Bladder Adenocarcinoma in a Constellation of Multiple Site Malignancies: An Unusual Case and Systematic Review

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods: A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.

Epidemiology of malignant brain tumors in Genova, Italy. 1993–2017

We present an updated analysis on the incidence of primary brain tumors in the Metropolitan Area of Genova, the capital of the northwestern Italian region Liguria.The number of cases and incidence rates for all malignant brain tumors, glioblastoma, malignant brain tumors other than glioblastoma, and brain tumors not otherwise specified were calculated for each of seven three-year and one-eighth four-year periods in which the quarter century 1993–2017 was divided. The rates were age-adjusted (AAR) using the 2013 European standard population, presented per 100,000 person-years and the average percentage change over the three-year period was calculated.The number of cases of all malignant brain tumors and glioblastoma was higher in males than in females in each three-year period and in the entire quarter century 1993–2017. During the latter, the average three-year percentage change in AARs for all brain tumors was minimal [0.6 (95% C.I. = -1.0/2.1) %] while for glioblastoma there was a change of 5.3 (95% C.I. = -0.4/11.3) %. The partially concurrent decline in the incidence rates of malignant brain tumors other than glioblastoma or not otherwise specified suggests that the observed increase in the incidence rate of glioblastoma during 1993–2017 may have been at least partially linked to the improvement during the same period in sensitivity and specificity of the diagnosis of glioblastoma, depleting the reservoirs of other malignant or unspecified brain tumors. Research into possibly increased environmental risk factors (e.g., population exposure to ionizing radiation) for glioblastoma in Genova remains warranted.

Nuclear receptor E75/NR1D2 promotes tumor malignant transformation by integrating Hippo and Notch pathways.

Hormone therapy resistance and the ensuing aggressive tumor progression present a significant clinical challenge. However, the mechanisms underlying the induction of tumor malignancy upon inhibition of steroid hormone signaling remain poorly understood. Here, we demonstrate that Drosophila malignant epithelial tumors show a similar reduction in ecdysone signaling, the main steroid hormone pathway. Our analysis of ecdysone-induced downstream targets reveals that overexpression of the nuclear receptor E75, particularly facilitates the malignant transformation of benign tumors. Genome-wide DNA binding profiles and biochemistry data reveal that E75 not only binds to the transcription factors of both Hippo and Notch pathways, but also exhibits widespread co-binding to their target genes, thus contributing to tumor malignancy. We further validated these findings by demonstrating that depletion of NR1D2, the mammalian homolog of E75, inhibits the activation of Hippo and Notch target genes, impeding glioblastoma progression. Together, our study unveils a novel mechanism by which hormone inhibition promotes tumor malignancy, and describes an evolutionarily conserved role of the oncogene E75/NR1D2 in integration of Hippo and Notch pathway activity during tumor progression.

The epidemiological characteristics of invasive pulmonary aspergillosis and risk factors for treatment failure: a retrospective study

ObjectiveThe incidence of invasive pulmonary aspergillosis (IPA) is increasing gradually. This study analysed the epidemiological characteristics and prognostic factors of patients with IPA and explored the risk factors affecting prognosis.Materials and methodsThe clinical data and treatment of 92 patients with IPA were retrospectively analysed, and the patients were followed for 12 weeks. Patients were divided into an effective treatment group and an ineffective treatment group, and the risk factors affecting prognosis were discussed.ResultsA total of 92 patients met the IPA inclusion criteria, and the most common genus of Aspergillus was Aspergillus fumigatus. The incidence of IPA was highest in patients with malignant tumours. IPA often coexisted with infections caused by other pathogens. We divided the patients into an effective treatment group and an ineffective treatment group according to prognosis. Compared with those in the effective treatment group, the procalcitonin (PCT) level, lactate dehydrogenase-to-albumin ratio (LDH/ALB) and neutrophil-to-lymphocyte ratio (NLR) in the ineffective treatment group were greater, the serum albumin level was lower, and the imaging findings revealed less nodules and bronchial wall thickening (P < 0.05). Among these factors, a decrease in the serum albumin concentration, an increase in the PCT level, coinfection and less bronchial wall thickening on imaging were independent risk factors for aspergillosis treatment failure.ConclusionA decreased albumin level, an elevated PCT level, coinfection, and less bronchial wall thickening were independent risk factors for treatment failure in patients with IPA. Attention should be given to the albumin level, coinfection status and imaging findings of patients.

Huaier promotes sensitivity of colorectal cancer to oxaliplatin by inhibiting METTL3 to regulate the Wnt/β‑catenin signaling pathway.

Colorectal cancer (CRC) ranks fifth in terms of incidence rate and mortality among malignant tumors in China. Oxaliplatin (OXA) is a first‑line drug for the clinical treatment of CRC, but its antitumor effect is limited because of the development of drug resistance. The present study aimed to investigate whether the traditional Chinese medicine Huaier can regulate the Wnt/β‑catenin signaling pathway by affecting the expression of METTL3, thereby promoting the sensitivity of HCT‑8/L cells to OXA. The expression of METTL3 was analyzed based on the UCSC Xena and Gene Expression Omnibus databases. Silent METTL3 and overexpression METTL3 models were constructed, and Cell Counting Kit‑8 and flow cytometry were used to detect the effects of Huaier on the viability and apoptosis of HCT‑8/L cells. Western blotting, reverse transcription‑quantitative PCR, nuclear cytoplasmic separation and immunofluorescence were used to detect the effects of Huaier on the expression of METTL3, Pgp, Wnt/β‑catenin signaling pathway‑related proteins, apoptosis‑related proteins and related mRNA. The results demonstrated that patients with high expression levels of METTL3 had a shorter overall survival period. The expression level of METTL3 significantly increased in drug‑resistant CRC cells. Silencing METTL3 promoted apoptosis of CRC cells and increased their sensitivity to OXA by inhibiting the Wnt/β‑catenin signaling pathway. Huaier downregulated the expression of METTL3, thereby promoting apoptosis of drug‑resistant CRC cells and increasing their sensitivity to OXA by inhibiting the Wnt/β‑catenin signaling pathway.

Artificial intelligence-enhanced infrared thermography as a diagnostic tool for thyroid malignancy detection

Introduction Thyroid nodules are common, and investigation is crucial for excluding malignancy. Increased intranodular vascularity is frequently observed in malignant tumors, which can be detected through increased skin surface temperatures using noninvasive infrared thermography. We aimed to develop a diagnostic tool for thyroid cancer using infrared thermal images combined with an artificial intelligence (AI) algorithm. Methods We conducted a prospective cross-sectional study involving participants with thyroid nodules undergoing thyroid surgery. Infrared thermal images were collected using a thermal camera on the day prior to surgery. In combination with the final thyroid pathological reports, we utilized a machine learning model based on the pre-trained ResNet50V2 model, a convolutional neural network, to evaluate diagnostic accuracy for malignancy diagnosis. Results The study included 98 participants, 58 with malignant thyroid nodules and 40 with benign thyroid nodules, as determined by pathological results. The AI-enhanced infrared thermal image analyses demonstrated good performance in distinguishing between benign and malignant thyroid nodules, achieving an accuracy of 75% and a sensitivity of 78%. These parameters were slightly lower than those of the AI-model predictor that integrated current practice using preoperative thyroid ultrasound findings and cytological results, yielding an accuracy of 81% and a sensitivity of 84%. Conclusions The infrared thermal images, assisted by an AI model, exhibit good performance in distinguishing thyroid malignancy from benign nodules. This imaging modality has great potential to be used as a noninvasive screening tool for adjunct evaluation of thyroid nodules.

A higher mortality in men compared to women with heart failure in primary care and ejection fraction equal to or more than 40%

ABSTRACT The aim of this study was to describe gender-related differences in characteristics and mortality in heart failure (HF) patients managed in primary care (PC). We included 1802 hF patients aged 77.5 ± 8.8 years (47% women) with ejection fraction (EF) ≥ 40% from the Swedish Heart Failure (SwedeHF) registry. The patients were divided by gender, and by heart failure with mildly reduced ejection fraction (HFmrEF; EF 40–49%) or heart failure with preserved ejection fraction (HFpEF; EF ≥ 50%). Men included in the study were younger (mean-age 76.4 vs 78.7 years, p < 0.0001) and showed a higher age-adjusted mortality (p < 0.0001). Men more often showed ischemic heart disease, 49% vs. 38% (p < 0.0001), atrial fibrillation, 56% vs. 50%, and diabetes, 25% vs. 17% (both p < 0.01). Women had higher blood pressure compared to men (p < 0.01), more commonly had kidney dysfunction (p < 0.01), and a worse functional capacity (p < 0.01). Cardiovascular diseases were the dominating causes of death in men and women (60% and 56%) but were less dominating in individuals with EF ≥ 50%, especially among women (56% in men vs. 46% in women). Among women with EF ≥ 50%, the mortality was dominated of mixed and unspecified diseases. Other important causes of death were cancer (15%) and chronic obstructive pulmonary disease (13%). Men managed in PC with HF and EF ≥ 40% have a higher age-adjusted mortality than women. Cardiovascular disease is the dominating cause of death in both genders. Other frequent causes of death were malignant tumors and respiratory diseases, illustrating the need to carefully diagnose and treat all associated comorbidities.

Dysregulation of miRNAs in Soft Tissue Sarcomas

MicroRNAs (miRNAs) are pivotal regulators of gene expression, influencing key cellular processes such as proliferation, differentiation, apoptosis, and metastasis. In the realm of sarcomas—a diverse group of malignant tumors affecting soft tissues and bone sarcomas—miRNAs have emerged as crucial players in tumorigenesis and tumor progression. This review delves into the intricate roles of miRNAs across various soft tissue sarcoma subtypes, including rhabdomyosarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, fibrosarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and malignant peripheral nerve sheath tumor (MPNST). We explore how dysregulated miRNAs function as oncogenes or tumor suppressors, modulating critical pathways that define the aggressive nature of these cancers. Furthermore, we discuss the diagnostic and prognostic potential of specific miRNAs and highlight their promise as therapeutic targets. By understanding the miRNA-mediated regulatory networks, this review aims to provide a comprehensive overview of current research while pointing towards future directions for miRNA-based therapies. Our findings underscore the potential of miRNAs to transform the landscape of sarcoma treatment, offering hope for more precise, personalized, and effective therapeutic strategies.

Fibroblast Heterogeneity in Hepatocellular Carcinoma and Identification of Prognostic Markers Based on Single-cell Transcriptome Analysis.

HCC is a malignant tumor with high morbidity and mortality. Fibroblasts play a key role in the tumor microenvironment (TME). However, the transcriptional regulatory mechanisms of fibroblasts remained unclear in HCC. The aim of this study was to explore the complex role of fibroblasts in hepatocellular carcinoma (HCC) and to reveal their transcriptional regulatory mechanisms. The goal of this study was to discover potential prognostic markers for HCC by analyzing the genetic variations and differentiation process of fibroblasts. Single-cell transcriptome data from the non-tumor liver site and primary tumor site of HCC were acquired from GSE149614, processed, and clustered using the Seurat pipeline. The inferCNV algorithm was applied to infer copy number variations (CNVs) in fibroblasts. Subsequently, the mechanism underlying the interaction between fibroblasts and other cells in the TME of HCC was analyzed using CellChat software. The trajectory of cellular differentiation of fibroblasts from normal state to malignant state was examined using Monocle 2. SCENIC analysis was performed to identify key transcription factors (TFs) in fibroblasts and assess their correlation with HCC prognosis. Finally, qRT-PCR and Transwell assays were carried out to analyze the mRNA expression and cell metastasis. We identified a total of nine different cell types (B cells, cycling cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, macrophages, plasma cells, and T cells) based on the single-cell transcriptomic data of HCC. Among them, fibroblasts were highly enriched at the primary tumor site, and their number increased with advanced stages. In addition, significant deletions were detected on chromosome 6p of fibroblasts, and genes in this region were remarkably enriched in pathways associated with antigen processing and presentation. Intercellular communication showed that epithelial cells regulated fibroblasts the most. The differentiation of fibroblasts was mainly accompanied by a transition from normal to malignant state. Importantly, CEBPD and FOSB, the TFs most associated with the putative timing of fibroblasts, were under-expressed in human hepatocytes and showed a significant correlation with HCC prognosis. Overexpressed CEBPD inhibited HCC cell migration and invasion. In conclusion, our study revealed that fibroblast recruitment and differentiation, as well as copy number loss at chromosome 6p, were associated with a higher degree of malignancy and immune dysfunction in HCC. The current discoveries provided new insights into the clinical treatment and diagnosis of HCC.

Estimation of the girls cost vaccination against human papillomavirus in the Siberian Federal District

Background. The non-declining cervical cancer incidence in the Siberian Federal District 16.30/0000 (in Russia - 13.80 /0000) necessitate preventive vaccination against the human papillomavirus (HPV).Aim. To evaluate the cost-effectiveness of HPV vaccination in girls aged 9-14 years in the Siberian Federal District as a whole and in the context of subjects with a 60, 80, 90 percent target cohort.Materials and methods. We studied the size of the female population aged 9-14 years in the constituent entities of the Siberian Federal District for 2022, the average total cost of the vaccine, information on the gross regional product per capita, form C51 “Distribution of deaths by gender, age groups and causes of death” of Tomsk region, 2022. Age-standardized rate per 100,000 population of morbidity and detection (in percentages) of pre-invasive cervix cancer (carcinoma in situ) in the Siberian Federal District were calculated per 100 newly diagnosed malignant cervix neoplasms in 2022.Results. In the Irkutsk, Tomsk regions, Altai and Krasnoyarsk territories age-standardized rate (16.6; 17.8; 16.3; 18.90 /0000, respectively), the detection rate of pre-invasive cancer was 48.0-82.4 %, which indicates on the effectiveness of measures for early cervical cancer diagnosis. In the Republics of Tyva, Altai, Khakassia, age-standardized rate (26.4; 20.1; 19.30 /0000, respectively), cancer in situ was diagnosed in 8.2-23.6 % of cases, which indicates an insufficient level and defects in the organization preventive examinations in medical institutions. In the first year of vaccination against HPV with 60 % coverage of a girls cohort 9-14 years old (n = 404,943), 9.3 billion rubles will be required, with 80 % coverage (539,924 girls) - more than 12.4 billion rubles, with 90 % coverage (607,415 girls) - more than 13.9 billion rubles for primary vaccination against HPV. In subsequent years, more than 2.5-2.8 billion rubles will be required annually. Over 5 years, with 90 % coverage of the population, the financial costs of vaccination will be (817.8 million rubles), and the subsequent 4 annual investments (163.6 million rubles per year). The economic damage caused by mortality from cervical cancer in the Tomsk region over five years (2018-2022) amounted to 3,166.4 million rubles.Conclusion. Using the example of the Tomsk region, it was noted that when comparing financial resources, the costs of vaccinating girls against HPV are 2.2 times less than the economic damage from cervical cancer mortality. Regional budget funding for girls vaccination in administrative territories is relevant before its integration into the national calendar of preventive vaccinations.

Errate: A Retrospective Study of 290 Patients with Resectable Benign and Malignant Gastric Neoplasms to Compare Postoperative Outcomes of Endoscopic Resection with and without the Internal Traction Method Using a Spring-and-Loop with Clip (S-O Clip).

The authors have identified an error in Table 5 concerning the dissection speed. It is currently listed as follows: S-O group 14.5±9.5 and Control group 25.1±18.9. However, this is incorrect. The correct values should be reversed: S-O group 25.1±18.9 and Control group 14.5±9.5.

Research trends and foci in chondrosarcoma: A bibliometric and network analysis.

Chondrosarcoma is 1 of the most common malignant bone tumors, with dedicated research being conducted by scientists worldwide. The purpose of this study was to guide researchers in identifying valuable scholars, institutions, and countries, provide recommendations for journal submissions, and explore research trends and hotspots in chondrosarcoma studies through literature analysis. Data for this study were collected from the Web of Science Core Collection website. The R package bibliometrix was utilized for citation metrics analysis, VOSviewer for network analysis, and CiteSpace for generating keywords citation burst maps. The analysis focused on publications from 2000 to 2023, identifying trends, authorship patterns, and collaboration networks. A total of 2085 articles were initially identified, but after excluding non-English articles and those outside the study's time range, 2022 articles were included. The field comprised 9954 author records, with an average of 6.37 coauthors per document and 13.9% international co-authorships. Publications in chondrosarcoma research have shown an average annual growth rate of 3.9%. The most influential author identified was Tang Chih-Hsin from China Medical University. Significant contributions came from China Medical University and Leiden University, with China showing a dramatic increase in publications while the United States maintained a leading position in the field. The study highlights an increasing trend in chondrosarcoma research publications and identifies key contributors and institutions. Cancer emerged as 1 of the most influential journals in the field. Future research is likely to focus on targeted therapy for refractory chondrosarcomas, indicating a potential new hotspot in the ongoing efforts to understand and treat this malignancy.

The concept of the liquid biopsy in the treatment of malignant eye tumours

The liquid biopsy is acutting-edge technique that involves analysing non-solid biological tissues, primarily blood but also ocular fluids, for the presence of cancer cells or fragments of tumour DNA. Unlike traditional biopsies, liquid biopsies are usually minimally invasive and can be performed more frequently, enabling continuous monitoring of disease progression and treatment efficacy. This article (and the associated series of articles) outlines the key developments in liquid biopsy, which include the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTC) and exosomal RNA and protein biomarkers. Techniques, such as digital droplet PCR and next-generation sequencing (NGS) have made it possible to detect even very low levels of ctDNA, which is crucial for early cancer detection and monitoring minimal residual disease. The detection of rare CTCs is enhanced by techniques, such as microfluidic devices and immunomagnetic separation. Multiomic approaches, whereby exosomal RNA, protein and ctDNA analyses are combined, help to create amore comprehensive picture of tumour biology, including insights into tumour heterogeneity, potentially leading to better diagnostic and prognostic tools and helping to predict treatment response and resistance. The challenges of liquid biopsy application, which will be described in the following article, include (a)standardization, (b)cost and accessibility, (c)validation and clinical utility. However, the liquid biopsy represents apromising frontier in the application of precision ocular oncology, with ongoing research likely to expand its applications and improve its effectiveness in the coming years.

The pivotal role of autophagy in the pathogenesis and therapy of medulloblastoma.

Medulloblastoma (MB) is the most frequent malignant brain tumor in children. MB originates from neural precursor cells in distinctive regions of the rhombic lip and their maturation occurs in the cerebellum or the brain stem during embryonal development. Autophagy is also referred to as self-eating' which is a catabolic process that often triggers cellular homeostasis through the salvaging of degenerated proteins as well as organelles. Autophagy influence cell survival via aberrant proteins that could accumulate within the cell and influence potential signaling and transport mechanisms. The role of autophagy in MB aggressiveness as well as tumorigenesis is a very complex process. This review targets specifically data reporting the key roles of autophagy in the pathogenesis and therapy of MB.

New Horizons in Cancer Progression and Metastasis: Hippo Signaling Pathway

The Hippo pathway is highly evolved to maintain tissue homeostasis in diverse species by regulating cell proliferation, differentiation, and apoptosis. In tumor biology, the Hippo pathway is a prime example of signaling molecules involved in cancer progression and metastasis. Hippo core elements LATS1, LATS2, MST1, YAP, and TAZ have critical roles in the maintenance of traditional tissue architecture and cell homeostasis. However, in cancer development, dysregulation of Hippo signaling results in tumor progression and the formation secondary cancers. Hippo components not only transmit biochemical signals but also act as mediators of mechanotransduction pathways during malignant neoplasm development and metastatic disease. This review confers knowledge of Hippo pathway core components and their role in cancer progression and metastasis and highlights the clinical role of Hippo pathway in cancer treatment. The Hippo signaling pathway and its unresolved mechanisms hold great promise as potential therapeutic targets in the emerging field of metastatic cancer research.

Perspectives on Ergodic Cancer Therapy Derived from Cloning Genome Chaos via In Vivo Rhabdomyosarcoma RA-2 Models: a Narrative Review.

This review explores articles concerning the experimental research cycle on genome instability in cell populations of highly malignant recurrent organotropic rhabdomyosarcoma RA- 2 in rats. Clonal analysis and cloning were pivotal components of this research, which relies on the frequency of cells with micronuclei and internuclear bridges to gauge the intensity of chromothripsis and break-fusion-bridge cycles. The efficacy of cloning, determined by these indicators, stemmed from the deliberate isolation of tumor stem cells, yielding clones in which chromothripsis activity and breakage-fusion-bridge cycles were sustained. Notably, it is plausible that the stem cells themselves, progenitors of these clones, harbor dicentric chromosomes and chromosomal fragments, contributing to the formation of "fatal micronuclei" in their karyotype. Cloning based on bridges and micronuclei has proven effective up to a certain threshold (15%-18%), reaffirming the predicted reproductive extinction of malignant cell populations under mutational pressure and genome chaos, as posited by the genetic theory of cell populations. Furthermore, this review highlights the potential of ergodic cancer therapy as a novel therapeutic strategy. Ergodic therapy offers promising prospects for late-stage and terminal malignant tumors, where conventional treatments may fall short due to advanced progression. Furthermore, by "enhancing chromothripsis" through the induction of additional micronuclei and bridges, ergodic cancer therapy seeks to increase genome chaos to a critical threshold, potentially halting malignant progression. This innovative approach presents opportunities to explore new drugs and targets for chromothripsis-based oncotherapy, addressing the pressing need for effective treatments in advanced stages of malignancy.