Common Cancer Research Articles

Prevalence of human papillomavirus genotypes in women of different ethnicity from rural northwestern Ecuador

BackgroundIn Ecuador, cervical cancer is the third most common cancer among women and the second most common cause of cancer-related death in women. Although HPV represents a serious public health problem worldwide, the information about its prevalence and genotypes in remote communities of Ecuador is limited. The aim of this study was to determine the distribution of HPV genotypes among ethnic minority women from two remote communities of the northwestern region of Ecuador: Afro-Ecuadorians and Chachis (Amerindian group).MethodsWe included 291 women who responded to a short survey and were screened for HPV by the amplification of the L1 gene and a nested multiplex PCR to detect 14 high risk (HR) genotypes. A survey collected information on ethnicity, age, community access, and sexual and gynecological history. We identified risk factors associated with HPV infection and co-infection using multivariate logistic regression to calculate odds ratio (OR) and Wald 95% confidence intervals (CI).ResultsOverall, HPV prevalence in the study cohort was 56%, and the five most common HR-HPV genotypes were HPV-58, -16, -68, -39, and -43; however, the distribution of HPV genotypes varied according to ethnicity. We identified lineage A (European variant) for HPV-16 and sublineage A2 for HPV-58 in both ethnic groups. Adjusting for ethnicity, age, community access, and number of sexual partners, we found that Afro-Ecuadorian women were less likely to have an HPV infection than Chachi women (OR: 0.49, 95% CI: 0.25, 0.96), and that participants in communities only accessible by river had 64% less chances of an HPV infection when compared to women in communities accessible by road (OR: 0.36, 95% CI: 0.19, 0.71), and women with 2 to 3 sexual partners had 2.47 times the odds of HPV infection than participants with 0–1 partners (OR: 2.47, 95% CI: 1.32, 4.6). Similar associations were observed with prevalence of co-infection.ConclusionsThis study provides baseline knowledge regarding the prevalence and distribution of HPV genotypes in ethnic groups of the northwestern coastal Ecuador and essential information for the implementation of appropriate HPV testing and vaccination program to prevent cervical cancer.

Prevalence of human papillomavirus genotypes in women of different ethnicity from rural northwestern Ecuador

BackgroundIn Ecuador, cervical cancer is the third most common cancer among women and the second most common cause of cancer-related death in women. Although HPV represents a serious public health problem worldwide, the information about its prevalence and genotypes in remote communities of Ecuador is limited. The aim of this study was to determine the distribution of HPV genotypes among ethnic minority women from two remote communities of the northwestern region of Ecuador: Afro-Ecuadorians and Chachis (Amerindian group).MethodsWe included 291 women who responded to a short survey and were screened for HPV by the amplification of the L1 gene and a nested multiplex PCR to detect 14 high risk (HR) genotypes. A survey collected information on ethnicity, age, community access, and sexual and gynecological history. We identified risk factors associated with HPV infection and co-infection using multivariate logistic regression to calculate odds ratio (OR) and Wald 95% confidence intervals (CI).ResultsOverall, HPV prevalence in the study cohort was 56%, and the five most common HR-HPV genotypes were HPV-58, -16, -68, -39, and -43; however, the distribution of HPV genotypes varied according to ethnicity. We identified lineage A (European variant) for HPV-16 and sublineage A2 for HPV-58 in both ethnic groups. Adjusting for ethnicity, age, community access, and number of sexual partners, we found that Afro-Ecuadorian women were less likely to have an HPV infection than Chachi women (OR: 0.49, 95% CI: 0.25, 0.96), and that participants in communities only accessible by river had 64% less chances of an HPV infection when compared to women in communities accessible by road (OR: 0.36, 95% CI: 0.19, 0.71), and women with 2 to 3 sexual partners had 2.47 times the odds of HPV infection than participants with 0–1 partners (OR: 2.47, 95% CI: 1.32, 4.6). Similar associations were observed with prevalence of co-infection.ConclusionsThis study provides baseline knowledge regarding the prevalence and distribution of HPV genotypes in ethnic groups of the northwestern coastal Ecuador and essential information for the implementation of appropriate HPV testing and vaccination program to prevent cervical cancer.

Unmutated RRAS2 emerges as a key oncogene in post-partum-associated triple negative breast cancer

BackgroundBreast cancer (BC) is the most common cancer in women, with triple negative BC (TNBC) accounting for 20% of cases. While early detection and targeted therapies have improved overall life expectancy, TNBC remains resistant to current treatments. Although parity reduces the lifetime risk of developing BC, pregnancy increases the risk of developing TNBC for years after childbirth. Although numerous gene mutations have been associated with BC, no single gene alteration has been identified as a universal driver. RRAS2 is a RAS-related GTPase rarely found mutated in cancer.MethodsConditional knock-in mice were generated to overexpress wild type human RRAS2 in mammary epithelial cells. A human sample cohort was analyzed by RT-qPCR to measure RRAS2 transcriptional expression and to determine the frequency of both a single-nucleotide polymorphism (SNP rs8570) in the 3’UTR region of RRAS2 and of genomic DNA amplification in tumoral and non-tumoral human BC samples.ResultsHere we show that overexpression of wild-type RRAS2 in mice is sufficient to develop TNBC in 100% of females in a pregnancy-dependent manner. In human BC, wild-type RRAS2 is overexpressed in 68% of tumors across grade, location, and molecular type, surpassing the prevalence of any previously implicated alteration. Still, RRAS2 overexpression is notably higher and more frequent in TNBC and young parous patients. The increased prevalence of the alternate C allele at the SNP position in tumor samples, along with frequent RRAS2 gene amplification in both tumors and blood of BC patients, suggests a cause-and-effect relationship between RRAS2 overexpression and breast cancer.ConclusionsHigher than normal expression of RRAS2 not bearing activating mutations is a key driver in the majority of breast cancers, especially those of the triple-negative type and those linked to pregnancy.

Metastatic onset of prostate carcinoma: A clinical and pathological challenge.

Prostate cancer is the second most common cancer, following lung cancer, and the fifth leading cause of cancer death in men worldwide. The onset of the disease, characterized by symptoms or changes caused by distant metastases, is rare and poses a challenge for clinicians and pathologists. We aimed to present a series of prostate carcinoma (PC) with unusual, histologically confirmed distant metastases (pM1) at the time of diagnosis, which raised suspicions of other types or origins of the primary tumor. Patients diagnosed with PC and distant metastases within a five-year timeframe (2017-2022) were extracted from the hospital database. The following data were collected: patient's age, imaging data, serum PSA level, and histopathological evaluation results. Patients with unusual distant metastases were selected and analyzed. We identified 10 patients in whom the diagnosis of PC was established following histopathological examination of tissue taken from distant metastatic sites (pM1). In three patients, the location of distant metastases was unusual: retroperitoneal, cranial/dural/epicranial and supradiaphragmatic lymph nodes which posed diagnostic challenges. Establishing the prostate origin of the tumor relied on immunohistochemical (IHC) investigation guided by clinical-imaging information. A metastasis of PC may rarely present as a cranial/dural tumor, retroperitoneal, or supradiaphragmatic lymphadenopathies in a man over the age of 50, but it should be taken into consideration. In the absence of correlated clinical, imaging, and histopathological/IHC data, diagnosing distant metastasis from PC is difficult, especially considering its potentially confusing IHC profile.

Pulmonary nodule detection in low dose computed tomography using a medical-to-medical transfer learning approach.

Lung cancer is the second most common cancer and the leading cause of cancer death globally. Low dose computed tomography (LDCT) is the recommended imaging screening tool for the early detection of lung cancer. A fully automated computer-aided detection method for LDCT will greatly improve the existing clinical workflow. Most of the existing methods for lung detection are designed for high-dose CTs (HDCTs), and those methods cannot be directly applied to LDCTs due to domain shifts and inferior quality of LDCT images. In this work, we describe a semi-automated transfer learning-based approach for the early detection of lung nodules using LDCTs. In this work, we developed an algorithm based on the object detection model, you only look once (YOLO) to detect lung nodules. The YOLO model was first trained on CTs, and the pre-trained weights were used as initial weights during the retraining of the model on LDCTs using a medical-to-medical transfer learning approach. The dataset for this study was from a screening trial consisting of LDCTs acquired from 50 biopsy-confirmed lung cancer patients obtained over 3 consecutive years (T1, T2, and T3). About 60 lung cancer patients' HDCTs were obtained from a public dataset. The developed model was evaluated using a hold-out test set comprising 15 patient cases (93 slices with cancerous nodules) using precision, specificity, recall, and F1-score. The evaluation metrics were reported patient-wise on a per-year basis and averaged for 3 years. For comparative analysis, the proposed detection model was trained using pre-trained weights from the COCO dataset as the initial weights. A paired t-test and chi-squared test with an alpha value of 0.05 were used for statistical significance testing. The results were reported by comparing the proposed model developed using HDCT pre-trained weights with COCO pre-trained weights. The former approach versus the latter approach obtained a precision of 0.982 versus 0.93 in detecting cancerous nodules, specificity of 0.923 versus 0.849 in identifying slices with no cancerous nodules, recall of 0.87 versus 0.886, and F1-score of 0.924 versus 0.903. As the nodule progressed, the former approach achieved a precision of 1, specificity of 0.92, and sensitivity of 0.930. The statistical analysis performed in the comparative study resulted in a -value of 0.0054 for precision and a -value of 0.00034 for specificity. In this study, a semi-automated method was developed to detect lung nodules in LDCTs using HDCT pre-trained weights as the initial weights and retraining the model. Further, the results were compared by replacing HDCT pre-trained weights in the above approach with COCO pre-trained weights. The proposed method may identify early lung nodules during the screening program, reduce overdiagnosis and follow-ups due to misdiagnosis in LDCTs, start treatment options in the affected patients, and lower the mortality rate.

Pulmonary nodule detection in low dose computed tomography using a medical-to-medical transfer learning approach.

Lung cancer is the second most common cancer and the leading cause of cancer death globally. Low dose computed tomography (LDCT) is the recommended imaging screening tool for the early detection of lung cancer. A fully automated computer-aided detection method for LDCT will greatly improve the existing clinical workflow. Most of the existing methods for lung detection are designed for high-dose CTs (HDCTs), and those methods cannot be directly applied to LDCTs due to domain shifts and inferior quality of LDCT images. In this work, we describe a semi-automated transfer learning-based approach for the early detection of lung nodules using LDCTs. In this work, we developed an algorithm based on the object detection model, you only look once (YOLO) to detect lung nodules. The YOLO model was first trained on CTs, and the pre-trained weights were used as initial weights during the retraining of the model on LDCTs using a medical-to-medical transfer learning approach. The dataset for this study was from a screening trial consisting of LDCTs acquired from 50 biopsy-confirmed lung cancer patients obtained over 3 consecutive years (T1, T2, and T3). About 60 lung cancer patients' HDCTs were obtained from a public dataset. The developed model was evaluated using a hold-out test set comprising 15 patient cases (93 slices with cancerous nodules) using precision, specificity, recall, and F1-score. The evaluation metrics were reported patient-wise on a per-year basis and averaged for 3 years. For comparative analysis, the proposed detection model was trained using pre-trained weights from the COCO dataset as the initial weights. A paired t-test and chi-squared test with an alpha value of 0.05 were used for statistical significance testing. The results were reported by comparing the proposed model developed using HDCT pre-trained weights with COCO pre-trained weights. The former approach versus the latter approach obtained a precision of 0.982 versus 0.93 in detecting cancerous nodules, specificity of 0.923 versus 0.849 in identifying slices with no cancerous nodules, recall of 0.87 versus 0.886, and F1-score of 0.924 versus 0.903. As the nodule progressed, the former approach achieved a precision of 1, specificity of 0.92, and sensitivity of 0.930. The statistical analysis performed in the comparative study resulted in a -value of 0.0054 for precision and a -value of 0.00034 for specificity. In this study, a semi-automated method was developed to detect lung nodules in LDCTs using HDCT pre-trained weights as the initial weights and retraining the model. Further, the results were compared by replacing HDCT pre-trained weights in the above approach with COCO pre-trained weights. The proposed method may identify early lung nodules during the screening program, reduce overdiagnosis and follow-ups due to misdiagnosis in LDCTs, start treatment options in the affected patients, and lower the mortality rate.

PET Imaging of Differentiated Thyroid Cancer with TSHR-Targeted [89Zr]Zr-TR1402.

Thyroid cancer is the most common endocrine cancer, with differentiated thyroid cancers (DTCs) accounting for 95% of diagnoses. While most DTC patients are diagnosed and treated with radioiodine (RAI), up to 20% of DTC patients become RAI refractory (RAI-R). RAI-R patients have significantly reduced survival rates compared to patients who remain RAI-avid. This study explores [89Zr]Zr-TR1402 as a thyroid-stimulating hormone receptor (TSHR)-targeted PET radiopharmaceutical for DTC. [89Zr]Zr-TR1402 was synthesized with a molar activity of 25.9 MBq/nmol by conjugating recombinant human TSH (rhTSH) analogue TR1402 to chelator p-SCN-Bn-deferoxamine (DFO) in a molar ratio of 3:1 (DFO/TR1402) and radiolabeling with 89Zr (t1/2 = 78.4 h, β+ = 22.7%). As TSHR is absent in commonly available DTC-derived cell lines, TSHR was reintroduced via stable transduction by delivering a lentivirus containing the full-length coding region of the human TSHR gene. Receptor-mediated uptake of [89Zr]Zr-TR1402 was evaluated in vitro in stably transduced TSHR+ and wild-type TSHR- DTC cell lines. In vivo PET imaging was performed on Days 1-3 postinjection in male and female athymic nude mice bearing TSHR+ and TSHR- xenografts, along with ex vivo biodistribution on Day 3 postinjection. In vitro uptake of 1 nM [89Zr]Zr-TR1402 was significantly higher in TSHR+ THJ529T (P < 0.0001) and FTC133 (P < 0.01) cells than in TSHR- THJ529T and FTC133 cells. This uptake was shown to be specific in both TSHR+ THJ529T (P < 0.0001) and TSHR+ FTC133 (P < 0.0001) cells by blocking uptake with 250 nm DFO-TR1402. In vivo PET imaging showed accumulation of [89Zr]Zr-TR1402 in TSHR+ tumors, which was the highest on Day 1. In the male FTC133 xenograft model, ex vivo biodistribution confirmed a significant difference (P < 0.001) in uptake between FTC133+ (1.3 ± 0.1%ID/g) and FTC133- (0.8 ± 0.1%ID/g) tumors. A significant difference (P < 0.05) in uptake was also seen in the male THJ529T xenograft model between THJ529T+ (1.8 ± 0.6%ID/g) and THJ529T- (0.8 ± 0.4%ID/g) tumors. The in vitro and in vivo accumulation of [89Zr]Zr-TR1402 in TSHR-expressing DTC cell lines support the continued preclinical optimization of this approach.

Applications of Biosensors in Bladder Cancer.

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

Germline Sequencing of DNA Damage Repair Genes in Two Hereditary Prostate Cancer Cohorts Reveals New Disease Risk-Associated Gene Variants.

Rare, inherited variants in DNA damage repair (DDR) genes have a recognised role in prostate cancer (PrCa) susceptibility. In addition, these genes are therapeutically targetable. While rare variants are informing clinical management in other common cancers, defining the rare disease-associated variants in PrCa has been challenging. Here, whole-genome and -exome sequencing data from two independent, high-risk Australian and North American familial PrCa datasets were interrogated for novel DDR risk variants. Rare DDR gene variants (predicted to be damaging and present in two or more family members) were identified and subsequently genotyped in 1963 individuals (700 familial and 459 sporadic PrCa cases, 482 unaffected relatives, and 322 screened controls), and association analyses accounting for relatedness (MQLS) undertaken. In the combined datasets, rare ERCC3 (rs145201970, p = 2.57 × 10-4) and BRIP1 (rs4988345, p = 0.025) variants were significantly associated with PrCa risk. A PARP2 (rs200603922, p = 0.028) variant in the Australian dataset and a MUTYH (rs36053993, p = 0.031) variant in the North American dataset were also associated with risk. Evaluation of clinicopathological characteristics provided no evidence for a younger age or higher-grade disease at diagnosis in variant carriers, which should be taken into consideration when determining genetic screening eligibility criteria for targeted, gene-based treatments in the future. This study adds valuable knowledge to our understanding of PrCa-associated DDR genes, which will underpin effective clinical screening and treatment strategies.

MiRNAs that regulate apoptosis in breast cancer and cervical cancer.

In today's world, one of the main problems is cancer, which still has a long way to go to cure it, and it brings a lot of financial and emotional costs to the people of society and governments. Breast cancer (BC) and cervical cancer (CC), two of the most common cancers, are caused by several genetic and environmental factors in women. These two cancers' involvement rate is higher than other cancers in women. microRNAs (miRNAs) are non-coding RNA molecules with a length of 18 to 24 nucleotides, which play an important role in post-translational changes. miRNAs themselves are divided into two categories, oncomiRs and tumor suppressors. OncomiRs have a part in tumor expansion and tumor suppressors prevent tumor development and progress. miRNAs can control cellular processes by regulating various pathways including autophagy, apoptosis, and signaling. Apoptosis is a type of programmed cell death that includes intrinsic and extrinsic pathways and is different from other cell death pathways such as necrosis and ferroptosis. Apoptosis controls the growth, differentiation, and death of cells by regulating the death of damaged and old cells, and since miRNAs are one of the factors that regulate apoptosis, and divided into two categories: pro-apoptotic and anti-apoptotic. We decided in this study to investigate the relationship between miRNAs and apoptosis in the most common women's cancers, BC and CC.

The edutainment program on knowledge, perception, and uptake of cervical cancer screening among Muslim women in Southern Thailand: a quasi experimental study

IntroductionCervical cancer is a significant global health concern and is the third most common cancer in women. Owing to their religious beliefs, Muslim women in Thailand are less likely to be screened for cervical cancer.ObjectiveThis study aimed to explore how a Health Belief Model (HBM) (HBM = Health Belief Model)-Based Edutainment Program affects the knowledge, perception, and uptake of cervical cancer screening among Muslim women in Thailand.MethodsA quasi-experimental study was conducted in two rural districts of Southern Thailand with 83 Muslim women (intervention = 42, control = 41). The assessment was conducted through face-to-face interviews at baseline, post-intervention, and at 3-month follow-up. The intervention included four sessions involving video clips, folk songs, and short films. Data analysis was performed using repeated-measures ANOVA (ANOVA = Analysis of Variance) at a significance level of 0.05.ResultsThere were significant differences in the mean score of knowledge and perception between the intervention and control groups post-intervention and at 3-month follow-up (p < 0.001). The mean scores of knowledge and perception in the intervention group significantly increased post-intervention and at 3-month follow-up (p < 0.001). The uptake of cervical cancer screening tests in the intervention group was approximately twice as high as that in the control group (90.47% vs. 51.21%).ConclusionThe findings revealed that the Edutainment Program could improve the knowledge, perception, and uptake of cervical cancer screening among Muslim women in Thailand. In future studies, the intervention suggests testing different population groups to improve access to primary care for everyone.

A transversal cross-sectional study of factors related to HPV vaccination status and cancer screening participation among French women aged 25–40

BackgroundIn 2020, uterine cervical cancer (UCC) was the 12th most common cancer among women in France and the 4th worldwide. French health authorities wanted to increase Human Papilloma Virus (HPV) vaccination and screening rates. There were still many barriers to these measures among young women, their families, and health professionals and teachers. Between 2014 and 2019, international studies found inconsistent effects of HPV vaccination on UCC screening. In 2022, a survey was conducted among women aged 25 to 40 in the Nord-Pas-de-Calais region to assess participation 1) in HPV vaccination and its barriers, 2) in UCC screening as a function of HPV vaccination status.MethodsData were collected using an anonymous online questionnaire distributed by QR code in 80 general practices randomly selected in the Nord-Pas-de-Calais region between January and June 2022. Results were analyzed bivariately using the Chi2 test, multivariately when numbers allowed, and in age subgroups (sensitivity analysis).Results407 complete questionnaires (for 602 participating women) were analyzed. In our sample, 41% of women aged 25 to 40 in the Nord-Pas-de-Calais region were vaccinated against HPV viruses in 2022. The risk factors for non-vaccination, after multivariable adjustment, were: the periods of eligibility for vaccination in the early days of French vaccination (2007–2012: odds ratio OR = 0.04 [95% CI, 0.02–0.09]; 2012–2017: OR = 0.5 [0.3–0.8]), information received from non-medical sources (OR = 0.3 [0.2–0.6]), and absence of information about vaccination (OR = 0.12 [0.05–0.27]). In our sample, 90% of women were screened for UCC. In bivariate analysis, women at risk of not being screened were those who were youngest, had been vaccinated against HPV, were not heterosexual, lived alone, had gynecological follow-up by their general practitioner, and did not have regular gynecological follow-up. Sensitivity analysis showed that the only risk factor significantly correlated with non-screening regardless of age group was lack of regular gynecological follow-up.ConclusionsParticipation in HPV vaccination and UCC screening is improved by medical education and gynecological follow-up. This multicenter study, limited by the relative youth of vaccination in France, should be repeated after 2037 to assess the possible effect of vaccination on screening.

The Role of the RNA Helicase DDX3X in Medulloblastoma Progression

Medulloblastoma is the most common pediatric brain cancer, with about five cases per million in the pediatric population. Current treatment strategies have a 5-year survival rate of 70% or more but frequently lead to long-term neurocognitive defects, and recurrence is relatively high. Genomic sequencing of medulloblastoma patients has shown that DDX3X, which encodes an RNA helicase involved in the process of translation initiation, is among the most commonly mutated genes in medulloblastoma. The identified mutations are 42 single-point amino acid substitutions and are mostly not complete loss-of-function mutations. The pathological mechanism of DDX3X mutations in the causation of medulloblastoma is poorly understood, but several studies have examined their role in promoting cancer progression. This review first discusses the known roles of DDX3X and its yeast ortholog Ded1 in translation initiation, cellular stress responses, viral replication, innate immunity, inflammatory programmed cell death, Wnt signaling, and brain development. It then examines our current understanding of the oncogenic mechanism of the DDX3X mutations in medulloblastoma, including the effect of these DDX3X mutations on growth, biochemical functions, translation, and stress responses. Further research on DDX3X’s mechanism and targets is required to therapeutically target DDX3X and/or its downstream effects in medulloblastoma progression.

Circular RNA Expression Profile in Cervical Cancer and Construction of the Circular RNA‑MicroRNA‑Messenger RNA Regulatory Network

Introduction. Cervical cancer (CC) remains the most common cancer in women worldwide. However, effective and specific biomarkers for the diagnosis and prognosis of cervical cancer are yet to be found. In recent years, the potential of circular RNAs (circRNAs) as new diagnostic, prognostic and therapeutic tools has received much attention. The current study involved an in-depth bioinformatics research to explore the circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in order to identify important molecular processes and biological pathways supposedly associated with CC. Materials and methods. The study collected data on the expression of circRNA (GSE102686), miRNA (GSE30656) and mRNA of target genes (GSE9750), based on the Gene Expression Omnibus (GEO) database, in squamous cell carcinoma of the cervix samples and normal squamous epithelium of the cervix, dividing them into study and control groups. Protein-protein interaction (PPI), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to further understand the function of circRNAs for their target genes. Results. A total of 105 differentially expressed circular RNAs (DECs), 144 differentially expressed microRNAs (DEMs), and 539 differentially expressed target genes (DEGs) were identified for cervical cancer. Concurrently, functional enrichment analysis of GO and KEGG pathways was performed for DEGs. Subsequently, searching databases for circRNA, miRNA and mRNA target genes, as well as PPI network analysis and functional enrichment revealed 3 DECs with significantly high expression levels (hsa_circ_0000745, hsa_circ_0084927 and hsa_circ_0002762), 6 DEMs with reduced expression levels (hsa -miR-145, hsa-miR-876-3p, hsa-miR-1229, hsa-miR-182, hsa-miR-520h and hsa-miR-1252) and 9 key genes such as ANGPT2, COL11A1, MEST, KIF20A, CLN6, FNDC3B, USP18, DLGAP5 and CXCL9, suggesting a potentially significant role in cervical cancer. Conclusion.Understanding the circRNA-miRNA-mRNA regulatory network is of great importance for evaluating the oncogenesis of CC, as well as discoverying new circRNAs as the main regulatory molecules in this network. This is considered to be a new direction in the diagnosis and targeted therapy of cervical cancer.

CALU promotes lung adenocarcinoma progression by enhancing cell proliferation, migration and invasion

BackgroundLung cancer is the second most common cancer with the highest mortality in the world. Calumenin as a molecular chaperone that not only binds various proteins within the endoplasmic reticulum but also plays crucial roles in diverse processes associated with tumor development. However, the regulatory mechanism of calumenin in lung adenocarcinoma remains elusive. Here, we studied the impact of calumenin on lung adenocarcinoma and explored possible mechanisms.Methods5-ethynyl-2’-deoxyuridine assay, colony formation, transwell and wound healing assays were performed to explore the effects of calumenin on the proliferation and migration of lung adenocarcinoma cells. To gain insights into the underlying mechanisms through which calumenin knockdown inhibits the migration and proliferation of lung adenocarcinoma, we performed Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis and Ingenuity Pathway Analysis based on transcriptomics by comparing calumenin knockdown with normal A549 cells.ResultsThe mRNA and protein levels of calumenin in lung adenocarcinoma are highly expressed and they are related to an unfavorable prognosis in this disease. Calumenin enhances the proliferation and migration of A549 and H1299 cells. Gene Set Enrichment Analysis revealed that knockdown of calumenin in A549 cells significantly inhibited MYC and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling pathways while activating interferon signals, inflammatory signals, and p53 pathways. Ingenuity pathway analysis provided additional insights, indicating that the interferon and inflammatory pathways were prominently activated upon calumenin knockdown in A549 cells.ConclusionsThe anti-cancer mechanism of calumenin knockdown might be related to the inhibition of MYC and KRAS signals but the activation of interferon signals, inflammatory signals and p53 pathways.

A Dual-Modal, Label-Free Raman Imaging Method for Rapid Virtual Staining of Large-Area Breast Cancer Tissue Sections.

As one of the most common cancers, accurate, rapid, and simple histopathological diagnosis is very important for breast cancer. Raman imaging is a powerful technique for label-free analysis of tissue composition and histopathology, but it suffers from slow speed when applied to large-area tissue sections. In this study, we propose a dual-modal Raman imaging method that combines Raman mapping data with microscopy bright-field images to achieve virtual staining of breast cancer tissue sections. We validate our method on various breast tissue sections with different morphologies and biomarker expressions and compare it with the golden standard of histopathological methods. The results demonstrate that our method can effectively distinguish various types and components of tissues, and provide staining images comparable to stained tissue sections. Moreover, our method can improve imaging speed by up to 65 times compared to general spontaneous Raman imaging methods. It is simple, fast, and suitable for clinical applications.

Circular RNA Expression Profile in Cervical Cancer and Construction of the Circular RNA‑MicroRNA‑Messenger RNA Regulatory Network

Introduction. Cervical cancer (CC) remains the most common cancer in women worldwide. However, effective and specific biomarkers for the diagnosis and prognosis of cervical cancer are yet to be found. In recent years, the potential of circular RNAs (circRNAs) as new diagnostic, prognostic and therapeutic tools has received much attention. The current study involved an in-depth bioinformatics research to explore the circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory network in order to identify important molecular processes and biological pathways supposedly associated with CC. Materials and methods. The study collected data on the expression of circRNA (GSE102686), miRNA (GSE30656) and mRNA of target genes (GSE9750), based on the Gene Expression Omnibus (GEO) database, in squamous cell carcinoma of the cervix samples and normal squamous epithelium of the cervix, dividing them into study and control groups. Protein-protein interaction (PPI), Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to further understand the function of circRNAs for their target genes. Results. A total of 105 differentially expressed circular RNAs (DECs), 144 differentially expressed microRNAs (DEMs), and 539 differentially expressed target genes (DEGs) were identified for cervical cancer. Concurrently, functional enrichment analysis of GO and KEGG pathways was performed for DEGs. Subsequently, searching databases for circRNA, miRNA and mRNA target genes, as well as PPI network analysis and functional enrichment revealed 3 DECs with significantly high expression levels (hsa_circ_0000745, hsa_circ_0084927 and hsa_circ_0002762), 6 DEMs with reduced expression levels (hsa -miR-145, hsa-miR-876-3p, hsa-miR-1229, hsa-miR-182, hsa-miR-520h and hsa-miR-1252) and 9 key genes such as ANGPT2, COL11A1, MEST, KIF20A, CLN6, FNDC3B, USP18, DLGAP5 and CXCL9, suggesting a potentially significant role in cervical cancer. Conclusion.Understanding the circRNA-miRNA-mRNA regulatory network is of great importance for evaluating the oncogenesis of CC, as well as discoverying new circRNAs as the main regulatory molecules in this network. This is considered to be a new direction in the diagnosis and targeted therapy of cervical cancer.

Diagnosis of acute leukemia in children: the impact of remote residence on the time to make a diagnosis

Background. Acute leukemia (AL) is the most common childhood cancer with an incidence rate of about 55–62 cases per 1 million children under 18 years of age. Acute leukemia is difficult to diagnose due to nonspecific symptoms, which are often hidden under the “masks” of other diseases. This problem is especially relevant for regions with a population of up to 100,000 people, where AL in children is diagnosed once every 2–5 years causing too low cancer alertness among pediatricians. Aim: to assess the delay in diagnosis depending on the areas of residence in the Tver region and area remoteness from the Tver Regional Clinical Children’s Hospital (RCC H). Material and Methods. The analysis included 35 patients hospitalized in the Department of Oncology and Hematology of the RCC H for the period from 2018 to 2023. The diagnoses were: ALL, C91.0 – 30 (86 %), AML , C92 – 3 (9 %), and AL of unspecified cell type (ALUCL ), C95.0 – 2 (5 %) patients. The mean age was 61 months. Thrombocytopenia and anemia at the time of diagnosis were found in 76 % and 78 %, respectively. Leukocytosis &gt;20×109/L was observed in 58 %, leukopenia &lt;3.5×109/L in 15 % of patients. In 97 % of cases, blasts (2 % to 95 %) were detected in peripheral blood. In the city of Tver (group 1) and the Tver region (group 2), 16 (46 %) and 19 (54 %) patients were identified, respectively. The mean age of patients in group 1 was 28.6 months and the mean age in group 2 was 72.3 months (p=0.1). Results. In group 1 and 2, ALL was diagnosed in 14 (88 %) and 16 (84 %), AML in 1 (6 %) and 2 (11 %) and ALUCL in 1 (6 %) and 1 (5 %) cases, p=0.6, 0.7 and 0.95, respectively. Delay in diagnosis in the general group (n=35) was observed &lt;2 weeks in 21 (60 %) cases, 2–4 weeks – in 7 (20 %), ≥4–≤8 weeks – in 4 (11 %) and &gt;8 weeks – in 3 (9 %) cases. Delayed diagnosis among patients living in the city of Tver and Tver region was observed &lt;2 weeks in 7 (44 %) vs 13 (68 %) cases, 2–4 weeks – in 6 (38 %) vs 3 (17 %), ≥4–≤8 weeks – in 1 (6 %) vs 1 (5 %) and &gt;8 weeks – in 2 (12 %) vs 2 (10 %) cases, respectively (p=0.37). There was no significant impact of the distance of the residence place from the level 3 children’s hospital providing specialized care (RCC H) on the time of diagnosis. With the removal of &lt;50 km the diagnosis delay &lt;2 weeks, 2–4 weeks, ≥4–≤8 weeks, &gt;8 weeks was observed in 36, 36, 21 and 7 %, respectively. With the removal of ≥50–≤100 km, the diagnosis was made in the period of 2–4 weeks in 100 % of cases. With the removal of &gt;100 km the diagnosis delay &lt;2 weeks, 2–4 weeks, ≥4–≤8 weeks, &gt;8 weeks was observed in 30, 30, 20 and 20 %, respectively (p=0.78). Conclusion. The distance from the third-level hospital did not affect the period of diagnosis of AL in children, which is achieved by holding daily on-line conferences with country hospitals and out-patient departments followed by the rapid hospitalization of children with suspected oncohematological disorders in the specialized department.

AK7-deficiency reversal inhibits ccRCC progression and boosts anti-PD1 immunotherapy sensitivity.

Clear cell renal cell carcinoma (ccRCC) is a common kidney cancer with subtle early symptoms, high recurrence rates, and low sensitivity to traditional treatments like radiotherapy and chemotherapy. Identifying novel therapeutic targets is critical. The expression level of adenylate kinases 7 (AK7) in ccRCC was examined by the TCGAportal and UALCAN databases. The effect of AK7 on proliferation, invasion and migration of ccRCC cell lines was evaluated by cell assay. The correlation between AK7 expression and prognosis, as well as its direct relationship with immunotherapy efficacy, was analyzed using CANCERTOOL and Kaplan-Meier plotter data. Moreover, the TISIDB database was used to study the relationship between AK7 and immune markers. The effect of overexpressed AK7 combined with PD1 monoclonal antibody on ccRCC was evaluated in animal experiments. The results showed that low level of AK7 expression was observed in ccRCC tissues. The expression of AK7 can regulate the proliferation, invasion, and migration of human ccRCC cell lines. The level of AK7 expression was associated with OS of ccRCC patients. This was potentially due to the negative connection between AK7 expression and CD8+ T cell depletion, indicating that immunotherapy might be less effective in individuals with low AK7 expression. Conversely, augmenting AK7 demonstrated an enhanced effectiveness of anti-PD1 therapy. The findings of our research strongly indicated that AK7 could serve as both a prognostic indicator and therapeutic target for patients with ccRCC. Moreover, the overexpression of AK7 combined with anti-PD1 held promising potential as a therapeutic approach for treating ccRCC.

Management of intrahepatic and perihilar cholangiocarcinomas: Guidelines of the French Association for the Study of the Liver (AFEF).

Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant primary liver cancer. iCCA may develop on an underlying chronic liver disease and its incidence is growing in relation with the epidemics of obesity and metabolic diseases. In contrast, perihilar cholangiocarcinoma (pCCA) may follow a history of chronic inflammatory diseases of the biliary tract. The initial management of CCAs is often complex and requires multidisciplinary expertise. The French Association for the Study of the Liver wished to organize guidelines in order to summarize the best evidence available about several key points in iCCA and pCCA. These guidelines have been elaborated based on the level of evidence available in the literature and each recommendation has been analysed, discussed and voted by the panel of experts. They describe the epidemiology of CCA as well as how patients with iCCA or pCCA should be managed from diagnosis to treatment. The most recent developments of personalized medicine and use of targeted therapies are also highlighted.