Search Results (2,796)

The antiproliferative and antibacterial activities of thiosemicarbazones increase markedly with the presence of metal ions. One of the factors determining the activity of metal thiosemicarbazone complexes is the coordination structure. In this study, the biological effects of new antimony (III) and bismuth (III) thiosemicarbazone complexes with different binding modes and geometrical structures were demonstrated. Three new complexes, with the formulae {[SbCl₃(µ₂-S-Hacptsc)(η¹-S-Hacptsc)], 2/3H₂O,1/3CH₂Cl₂}, {[SbCl₃(κ²-S,N-Hacpmtsc)(η¹-S-Hacpmtsc)₂CH₂Cl₂]}, and{[BiCl₃(η¹-S-Hbzmtsc)₃]·C₂H₅OH}, where Hacptsc: acetophenone thiosemicarbazone, Hacpmtsc: acetophenone-N-methyl thiosemicarbazone, Hbzmtsc: benzaldehyde-N-methyl thiosemicarbazone) were elucidated by different methods and deeply analyzed in accordance with their structure by X-ray structure analysis and Atoms-In-Molecules topological analysis. This analysis provided a deeper understanding of the coordination spheres of the Sb/Bi complexes. For instance, the first reported two binding modes of the same ligand are observed in a single crystal structure of antimony (III) halide complexes. Additionally, in one of the complexes, a solid-to-solid phase transition was detected and analyzed in detail. Those complexes, very unique in terms of their geometry, have also been tested for their in vitro cytotoxic activity against human adenocarcinoma cervical cancer (HeLa) cells, whereas antimony (III) complex 1is the most active complex of this study. Further, the antibacterial activity of the complexes has been screened against two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and two Gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) pathogenic bacteria. From the results, it is found that all the complexes exhibited significant activity against the Gram-negative pathogenic bacteria. Full article

Background: Determining the distribution of high-risk human papillomavirus (HR-HPV) types in histologic low-(LSIL) and high-grade (HSIL/CIN2+) squamous intraepithelial lesions through a diagnostic process in a cervical cancer prevention provides one of the key etiological factors behind further progression and persistence. Incorporating novel high-grade cervical lesion biomarkers such as p16/Ki67 dual staining (DS) alongside HPV typing has become important in detecting cervical precancers. Methods: Among 28,525 screening tests and 602 histology results, 559 cases with HR-HPV and histology results obtained from colposcopic biopsy were retrospectively analyzed, together with DS status. The χ² test with Bonferroni correction evaluated the differences in HR-HPV type prevalence and DS positivity across three histologic study groups. Results: A statistically significant difference in the prevalence of HPV 16 was observed between negative and HSIL/CIN2+ (p = 0.00027) groups, as well as between the LSIL/CIN1 and HSIL/CIN2+ groups (p = 0.00041). However, no significant difference was found between the negative and LSIL/CIN1 groups. Similarly, the DS positivity difference was significant between the negative and HSIL/CIN2+ (p < 0.0001) and between the LSIL/CIN1 and HSIL/CIN2+ groups (p < 0.0001), but there was no significant difference between the negative and LSIL/CIN1 groups. Conclusions: The study highlights the heterogeneous nature of HPV-related cervical pathologies, and the distinct risks associated with different cervical lesion grades, emphasizing the importance of HR-HPV type distribution and DS status. Full article

Background: Para-aortic lymphadenectomy can be used for both diagnostic and therapeutic purposes as it aids in staging, provides prognostic data, and influences the patient’s options for adjuvant therapy. However, there is still contention over its potential in treating cancer. A systematic review of the literature was performed to look into the published randomized controlled studies (RCTs) that have reported the effectiveness of lymphadenectomy. Methods: Five different electronic databases, including PubMed, Cochrane Library, Clinical trials.gov, ICTRP, and Embase, were used to conduct a comprehensive search. Original RCTs reporting on the impact of lymphadenectomy on the overall survival in various cancers were included. Information related to the study population, intervention, type of cancer, primary endpoints, and key findings of the study were extracted. Quality assessment of the selected studies was conducted using the Revised Cochrane Risk of Bias Tool Rob 2 for randomized trials. Results: A total of 1693 citations, with 1511 from PubMed, 80 from the Cochrane Library, 67 from Embase, 18 from ICTRP, and 17 from Clinicaltrials.gov were retrieved. Preliminary screening was performed, and after applying selection criteria, nine articles were included in the final qualitative analysis. The total number of patients was 4231, and the sample size ranged from 70 to 1408. Among these nine studies, four studies were on genital cancers (two ovarian cancers, one endometrial cancer, and one cervical cancer); four on digestive cancers (advanced gastric cancers); and one on urinary cancer (advanced bladder cancer). These studies reported that para-aortic lymphadenectomy did not improve overall survival and disease-free survival in advanced ovarian cancers, early endometrial cancers, advanced gastric, and bladder cancers. All of the studies had a low risk of bias. Conclusions: Para-aortic lymphadenectomy is not advised in advanced ovarian cancers, early endometrial cancers with low risks, advanced gastric cancers, and bladder cancers. SNB could be an alternative to lymphadenectomy for ovarian cancer in the future. Clinicians should inform patients regarding the benefits of para-aortic lymphadenectomy in terms of survival and the potential risks associated with it. Full article

The high-risk Human Papillomavirus (HR-HPV) is the causal agent of different human cancers such as cervical, vulvar, and oropharynx cancer. This is because persistent HR-HPV infection alters several cellular processes involved in cell proliferation, apoptosis, immune evasion, genomic instability, and cellular transformation. The above is mainly due to the expression of early expression proteins of HR-HPV, which interact and alter these processes. HR-HPV proteins have even been shown to regulate redox state and mitochondrial metabolism, which has been suggested as a risk factor for cancer development. Redox state refers to a balance between reactive oxygen species (ROS) and antioxidants. Although ROS regulates cell signaling, high levels of ROS generate oxidative stress (OS). OS promotes damage to DNA, proteins, carbohydrates, and lipids, which causes mutation accumulation and genome instability associated with cancer development. Thus, OS has been associated with the establishment and development of different types of cancer and has recently been proposed as a cofactor in HR-HPV-associated cancers. However, OS also induces cell death, which can be used as a target for different molecules, such as phytochemicals. Furthermore, phytochemicals target HPV oncoproteins E6 and E7, causing their degradation. Because phytochemicals could induce OS and target HPV oncoproteins, we hypothesize that these compounds induce cell death in HPV-associated cancers. Since the redox state is crucial in developing, establishing, and clearing HR-HPV-associated cancer, this review focuses on evidence for using phytochemicals as therapeutic agents that target HPV proteins and the redox state to induce the elimination of HPV-related cancers. Full article

Background: Health disparities related to socio-economic factors impact access to preventive health interventions. The PRECEDE–PROCEED model, a multidimensional approach to health promotion, has been adapted to optimise cancer screening programs in Lombardy, Italy, addressing these disparities. Methods: This study evaluated the application of systemic audits based on the PRECEDE–PROCEED model across Lombardy cancer screening programs. A systematic region-wide audit was performed in 2019, and follow-up audits were performed in 2022–2023. Data were collected using structured analysis methodologies, including epidemiological, behavioural, and organisational assessments. Results: The 2019 audit showed strengths in participation and quality standards but identified challenges in cervical cancer screening coverage and waiting times for assessments. Improvements plans included the digitisation of processes and stakeholder engagement. The 2022–2023 audits reported increased coverage for breast and colorectal screenings, but a slight decline in participation rates and examination coverage. Organisational improvements were noted, yet gaps in training and equity-targeted actions remained. Conclusion: The PRECEDE–PROCEED model audits led to notable improvements in the quality and equity of cancer screening programs in Lombardy. Sustained focus on digital integration, continuous re-training, and targeted equity interventions is essential for further progress. Full article

This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm⁻² ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment. Full article

Copper is a vital trace element in oxidized and reduced forms. It plays crucial roles in numerous biological events such as redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy, and immune modulation. Maintaining the balance of copper in the body is essential because its deficiency and excess can be harmful. Abnormal copper metabolism has a two-fold impact on the development of tumors and cancer treatment. Cuproptosis is a form of cell death that occurs when there is excessive copper in the body, leading to proteotoxic stress and the activation of a specific pathway in the mitochondria. Research has been conducted on the advantageous role of copper ionophores and chelators in cancer management. This review presents recent progress in understanding copper metabolism, cuproptosis, and the molecular mechanisms involved in using copper for targeted therapy in cervical cancer. Integrating trace metals and minerals into nanoparticulate systems is a promising approach for controlling invasive tumors. Therefore, we have also included a concise overview of copper nanoformulations targeting cervical cancer cells. This review offers comprehensive insights into the correlation between cuproptosis-related genes and immune infiltration, as well as the prognosis of cervical cancer. These findings can be valuable for developing advanced clinical tools to enhance the detection and treatment of cervical cancer. Full article

Radioresistance poses a significant challenge in the effective treatment of cervical cancer, often leading to poor patient outcomes. MicroRNA-21 (miR-21) and MicroRNA-145 (miR-145) are oncogenic micro-RNAs associated with various cancers, including cervical cancer, but their potential as predictive biomarkers for radioresistance remains underexplored. This study aimed to investigate the association between miR-21 and miR-145 expressions and the response to radiation therapy in cervical cancer patients. An analytical cross-sectional study was conducted on 140 subjects with cervical cancer stages IIIB and IVA who received definitive radiotherapy. miR-21 and miR-145 expressions were measured using real-time reverse transcriptase–polymerase chain reaction (RT-qPCR). A total of 102 subjects (72.9%) were classified as having stage III cervical cancer, and 38 subjects (27.1%) were classified as having stage IV cervical cancer. Disease progression occurred in 60.7% of subjects. The cut-off value for miR-21 expression was 0.00088 nmol/(mg/mL) (AUC 0.676, sensitivity 70.8%, specificity 50.8%), and a higher expression was significantly associated with radioresistance (p = 0.010). miR-145, with a cut-off of 0.0239 nmol/(mg/mL) (AUC 0.612, sensitivity 67.5%, specificity 45.5%), showed no significant association with treatment response (p = 0.132). Combining miR-21 and miR-145 (AUC 0.639, sensitivity 68.6%, specificity 46.9%, p = 0.063) did not significantly improve the predictive accuracy. This study suggests that an elevated miR-21 expression is significantly associated with radioresistance in cervical cancer patients, while miR-145 expression shows no significant correlation with treatment response. Additionally, combining miR-21 and miR-145 does not enhance the predictive power. Full article

(1) Background: In 2018 FIGO reclassified tumors confined to the cervix larger than 4 cm as stage IB3. Although concurrent CTRT has been the standard of care and surgery the alternative, optimal management remains controversial due to the lack of direct comparison between surgery and CTRT. (2) Methods: This prospective observational study investigated the efficacy, safety and oncologic outcomes of nerve-sparing laparoscopic radical hysterectomy (nsLRH) for FIGO stage IB3 cervical cancer patients (IB3). From 2009 to 2023, IB3 patients underwent laparoscopic pelvic lymphadenectomies with frozen section analysis, followed by a nsLRH if the lymph nodes were tumor-free. No uterine manipulator was used and the vaginal cuff was sealed before retrieving the specimen. Intermediate-risk patients were under close observation without adjuvant therapy. Outcomes were monitored until 2023. (3) Results: During the study period, 74 IB3 patients were treated. Sixty-eight (91.9%) underwent a nsLRH. A complete resection with negative margins was achieved in all cases. At a median of 68 months of follow-up, the disease-free survival (DFS) rate was 89.7% and the overall survival (OS) rate was 93.1%. The overall complication rate was 23.5% and there were no grade 4–5 complications. (4) Conclusions: In patients with IB3 cervical cancer, a nsLRH is safe and effective. While awaiting the results from ongoing randomized trials, these findings support nsLRH as a viable treatment. Full article

Background: This study, conducted at a regional Thai hospital, assesses the comparative efficacy of self-collected versus clinician-collected samples for HPV detection using the Cobas 8800 system among Thai women aged 30–60. Methods: Our methodology involved analyzing 1541 self-collected and 1398 clinician-collected samples. Results: The results show a statistically significant mean difference in cycle threshold (Ct) values favoring clinician-collected samples (1.53; 95% CI: 1.18–1.87, p < 0.0001). This pattern was consistent across various age groups, with the most pronounced differences noted in the oldest cohort (50–59 years), suggesting higher detection efficiency in clinician-collected samples. The study further explored the correlation of Ct values with cytological and histological outcomes, where clinician-collected samples demonstrated superior diagnostic performance, particularly in identifying LSIL and HSIL conditions, evidenced by AUC values of 0.793 and 0.866, respectively. While self-sampling remains a viable method, with sensitivity reaching up to 48.84% for LSIL and 46.15% for HSIL, clinician collection proved more accurate, likely influencing future national screening policies. Conclusions: This work underscores the need for robust sample collection methods and the importance of ongoing enhancements to self-sampling assays and techniques to ensure their efficacy in cervical cancer screening programs. Full article

Background/Objectives: To analyze the spatial distribution of HPV vaccination coverage in relation to sociodemographic variables in a state of Southern Brazil. Methods: This was an ecological, retrospective study with secondary data from the Department of Information Technology of the Unified Health System/Ministry of Health from 2015 to 2022. The cohort method was used to calculate vaccination coverage. Geographically weighted regression was used for the independent variables. Results: There was a 22.04% reduction in vaccination between the first and second doses. Coverage with the first dose of the vaccine reached 95.17% for the female population, 64.67% for the male population, and 79.57% for both sexes. In 50.62% of cities, coverage exceeded 90% for both sexes. In 80.45% of cities, the recommended coverage for females was achieved. The variable municipal performance was positively significant for the increase in vaccination coverage in 45.45% of the regions for girls, 18.18% for boys, and 36.36% for both sexes. The family health strategy variable was significant in 9.09% of the regions for girls and both sexes. The education variable showed an inverse significance for girls in 40.90%, for boys in 18.18%, and for both sexes in 36.36% of the regions. Conclusions: HPV vaccination declined between the first and second doses, with high first-dose coverage among females and moderate coverage among males. Municipal performance notably impacted coverage, particularly for girls. The family health strategy was relevant in specific regions, while educational factors had a variable effect. Addressing these variables may enhance vaccination coverage and minimize the gap between doses. Full article

Cervical cancer is almost entirely preventable and treatable when detected early, making its elimination within reach for Canada and the world. However, cervical cancer is now the fastest-increasing cancer (+3.7% per year since 2015) in Canada as of 2023, marking the first significant increase in cervical cancer incidence since 1984. The human papillomavirus (HPV) vaccine and cervical screening are key preventive measures, with targets set by the WHO and the Canadian Partnership Against Cancer (CPAC) to eliminate cervical cancer in Canada by 2030 and 2040, respectively. These targets include increasing HPV vaccination rates, implementing primary HPV screening, and improving follow-up for abnormal HPV+ results. However, Canada’s progress has been impeded by significant challenges. As of the most recent data, HPV vaccine coverage rates in Canada range from 47% to 81%, with an estimated national HPV vaccination completion rate of 64% in Canada, far below the target of 90% by 2025 set by the CPAC. With the exception of British Columbia and Prince Edward Island, the adoption of HPV DNA testing as the primary screening method has been slow across the Canadian provinces and territories despite its superior sensitivity compared with traditional cytology. This article reviews the current state of HPV vaccination and screening in Canada, emphasizing the need for coordinated efforts, transparency, and resource sharing to overcome barriers. Key recommendations include the dissemination of accessible educational materials, partnerships, and collaboration, including nationwide task forces and roundtables, and the implementation of standardized guidelines for HPV screening. Achieving cervical cancer elimination requires a united approach involving federal, provincial, and territorial health authorities, researchers, clinicians, NGOs, community groups, and patients’ voices working together to ensure consistent, effective, timely, and meaningful cervical cancer prevention strategies are used across the country. Full article

Background: Cancer is one of the most significant threats to human health. Following surgical excision, chemotherapy is an effective strategy against remaining cancer cells. 4-hexylresorcinol (4-HR) has anti-cancer properties and exhibits hydrophobicity-induced aggregation in the blood that has trouble with targeted tumor delivery and cellular uptake of the drug. The purpose of this study is to encapsulate 4-HR into solid lipid nanoparticles (SLNs) to enhance its anti-cancer effect by avoiding aggregation and facilitating cellular uptake. Methods: 4-HR SLNs were prepared via hot melt homogenization with sonication. SLN characteristics were assessed by analyzing particle size, zeta potential, and drug release. Cytotoxicity, as an indicator of the anti-cancer effect, was evaluated against HeLa (cervical cancer in humans), A549 (lung cancer in humans), and CT-26 (colon carcinoma in mice) cell lines. Results: Particle size ranged from 169.4 to 644.8 nm, and zeta potential ranged from −19.8 to −40.3 mV, which are conducive to cellular uptake. Entrapment efficiency (EE) of 4-HR was found to be 75.0—96.5%. The cytotoxicity of 4-HR-loaded SLNs demonstrated enhanced anti-cancer effects compared to pure 4-HR. The enhancement of anti-cancer effects depended on reduced particle size based on cellular uptake, the EE, and the cell type. Conclusions: These findings imply that 4-HR-loaded SLN is a promising strategy for chemotherapy in cancer treatment. Full article

A 54-year-old female patient diagnosed with Stage IIIb squamous cell carcinoma (cT2aN3M0) initially received chemoradiotherapy. Two years after initial treatment, cancer relapse led to the administration of nivolumab, which was halted due to the development of drug-induced pneumonitis. Subsequent management with prednisolone and eight different cytotoxic agents failed to prevent metastasis to the cervical lymph nodes. The tumor’s programmed death-ligand 1 (PD-L1) expression rate was recorded at 10%. Four years after her diagnosis, the patient received a ninth-line therapy combining cisplatin, gemcitabine, and necitumumab, followed by palliative neck radiation due to increasing lymph node size. Remarkable tumor regression occurred three months after introducing atezolizumab as the tenth-line treatment, suggesting that previous treatments, particularly radiotherapy and cisplatin, might have enhanced PD-L1 expression, aligning with the existing literature. This case highlights the urgent need for further research to elucidate the intricate interplay between treatment history and PD-L1 expression in squamous cell carcinoma, emphasizing the importance of accumulating case studies to inform therapeutic strategies. Full article

Background: Prior preclinical studies showed promising antitumor activity and an acceptable safety profile associated with radiopharmaceuticals for patients with metastatic, persistent, or recurrent uterine cervix cancers. Whether the addition of a radiopharmaceutical to chemotherapy would significantly increase progression-free survival in such patients is untested. Our retrospective study sought to associate the line of treatment and progression-free survival as benchmarks for next-generation radiopharmaceutical development. Methods: We grouped metastatic, persistent, or recurrent uterine cervix cancer patients not amenable to curable surgery or radiotherapy between 2002 and 2023 by the line of doublet, triplet, and quadruplet chemotherapy or another intervention. After the first-line treatment, patients were monitored for radiographic progression every three months for up to three years. The primary endpoints were the first and any second or third progression-free survival intervals. Results: A total of 127 patients contributed demographic, tumor, line of treatment, and outcome data with a median follow-up of 18 months (25–75% interquartile range: 9 to 37 months). After the first-line treatment, 113 patients had local or distant progression or died from any cause, most often death from the disease (67%). Median progression-free survivals were 5.5 months (95% confidence interval: 4.8–6.0 months), 5.3 months (95% confidence interval: 4.5–6.3 months), and 3.0 months (95% confidence interval: 2.1–3.7 months) for the first-, second-, and third-line treatments, respectively. For a first-line cisplatin-containing regimen, the median progression-free survival was 6.5 months (95% confidence interval: 5.5–7.7 months). Conclusions: This study highlights the limited efficacy of current treatments for metastatic, persistent, or recurrent uterine cancer patients. A five-month progression-free survival might serve as a benchmark for the development of novel therapies in clinical efficacy trials, such as radiopharmaceuticals. Full article