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Background: Reprogramming of cellular metabolism is a pivotal mechanism employed by tumor cells to facilitate cell growth, proliferation, and differentiation, thereby propelling the progression of cancer. A comprehensive analysis of the transcriptional and metabolic landscape of cervical squamous cell carcinoma (CSCC) at high resolution could greatly enhance the precision of management and therapeutic strategies for this malignancy. Methods: The Air-flow-assisted Desorption Electrospray Ionization Mass Spectro-metric Imaging (AFADESI-MSI) and Spatial Transcriptomics techniques (ST) were employed to investigate the metabolic and transcription profiles of CSCC and normal tissues. For clinical validation, the expression of ASCT2(Ala, Ser, Cys transporter 2) was assessed using immune histochemistry in 122 cases of cervical cancer and 30 cases of cervicitis. Results: The AFADESI-MSI findings have revealed metabolic differences among different CSCC patients. Among them, the metabolic pathways of glutamine show more significant differences. After in situ detection of metabolites, the intensity of glutamate is observed to be significantly higher in cancerous tissue compared to normal tissue, but the intensity is not uniform. To elucidate the potential factors underlying alterations in glutamine metabolism across tissues, we employ ST to quantify mRNA levels. This analysis unveils significant perturbations in glutamine metabolism accompanied by extensive heterogeneity within cervical cancer tissues. After conducting a comprehensive analysis, it has been revealed that the differential expression of ASCT2(encoded by SLC1A5) in distinct regions of cervical cancer tissues plays a pivotal role in inducing heterogeneity in glutamine metabolism. Furthermore, the higher the expression level of ASCT2, the higher the intensity of glutamate is in the region. Further verification, it is found that the expression of ASCT2 protein in CSCC tissues is significantly higher than that in normal tissues (105/122, 86.07%). Conclusions: This finding suggests that the variation in glutamine metabolism is not uniform throughout the tumor. The differential expression of ASCT2 in different regions of cervical cancer tissues seems to play a key role in causing this heterogeneity. This research has opened up new avenues for exploring the glutamine metabolic characteristics of CSCC which is essential for developing more effective targeted therapies. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan–Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Reprogramming of cellular metabolism is a pivotal mechanism employed by tumor cells to facilitate cell growth, proliferation, and differentiation, thereby propelling the progression of cancer. A comprehensive analysis of the transcriptional and metabolic landscape of cervical squamous cell carcinoma (CSCC) at high resolution could greatly enhance the precision of management and therapeutic strategies for this malignancy. Methods The Air-flow-assisted Desorption Electrospray Ionization Mass Spectro-metric Imaging (AFADESI-MSI) and Spatial Transcriptomics techniques (ST) were employed to investigate the metabolic and transcription profiles of CSCC and normal tissues. For clinical validation, the expression of ASCT2(Ala, Ser, Cys transporter 2) was assessed using immune histochemistry in 122 cases of cervical cancer and 30 cases of cervicitis. Results The AFADESI-MSI findings have revealed metabolic differences among different CSCC patients. Among them, the metabolic pathways of glutamine show more significant differences. After in situ detection of metabolites, the intensity of glutamate is observed to be significantly higher in cancerous tissue compared to normal tissue, but the intensity is not uniform. To elucidate the potential factors underlying alterations in glutamine metabolism across tissues, we employ ST to quantify mRNA levels. This analysis unveils significant perturbations in glutamine metabolism accompanied by extensive heterogeneity within cervical cancer tissues. After conducting a comprehensive analysis, it has been revealed that the differential expression of ASCT2(encoded by SLC1A5) in distinct regions of cervical cancer tissues plays a pivotal role in inducing heterogeneity in glutamine metabolism. Furthermore, the higher the expression level of ASCT2, the higher the intensity of glutamate is in the region. Further verification, it is found that the expression of ASCT2 protein in CSCC tissues is significantly higher than that in normal tissues (105/122, 86.07%). Conclusions This finding suggests that the variation in glutamine metabolism is not uniform throughout the tumor. The differential expression of ASCT2 in different regions of cervical cancer tissues seems to play a key role in causing this heterogeneity. This research has opened up new avenues for exploring the glutamine metabolic characteristics of CSCC which is essential for developing more effective targeted therapies.

Abstract Objective miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.

Objectives: Lactic acid metabolism, a hallmark of carcinogenesis, may play potential roles in cervical carcinoma, assisting the prognosis prediction. Materials and Methods: A regression analysis was conducted to identify the ones with the most frequent variation in mutations and CNV changes in lactate metabolism‐related (L‐related) genes, after which a prognostic nomogram was built based on selected genes and clinical features by machine learning methods. Results: EGLN1, IL1, IL12RB1, ENO1, and 10 other genes had the most frequent changes and prognostic differences in overall survival (OS). The lactated associated risk (LAR) score model can distinguish the patients in OS (p = 0.046, HR = 101.9, 95%CI 1.1–9447.6), and together with clinical features has a higher AUC (AUC = 0.839). Furthermore, CD8+ T, activated CD4+ memory T and resting mast cells were significantly negatively associated with the LAR score. Conclusions: Lactic acid metabolism is closely related to the prognosis of cervical carcinoma, where the immune microenvironment may play an important role. [ABSTRACT FROM AUTHOR]

Jackfruit leaf protein hydrolysates obtained from the enzymatic hydrolysis of leaf protein concentrate with gastrointestinal enzymes have shown good techno-functional properties and high antioxidant capacity. However, molecular weight, antiproliferative activity, cytotoxicity and the ability to reduce reactive oxygen species (ROS) are still unknown. Therefore, this study aimed to evaluate the effect of jackfruit leaf protein hydrolysates obtained by enzymatic hydrolysis with pepsin and pancreatin at different hydrolysis times (30–240 min) on molecular weights, cytotoxicity, antiproliferation of cancer cells, and the reduction of reactive oxygen species in H2O2-induced HaCaT cells. The electrophoretic profile indicated that H-Pep contains peptides with molecular weights between 25 − 20 kDa. Meanwhile, H-Pan is composed of molecular weight products between 25 − 20 kDa and < 20 kDa. H-Pan and H-Pep (125–500 µg/mL) did not show significant cytotoxicity on HaCaT (human keratinocytes) and J774A.1 (murine macrophage cells). Antiproliferative activity was achieved in human cervical, ovarian, and liver cancer cells. H-Pan-240 min (1000 µg/mL) reduced the cell viability of cervical cancer cells by 23% while H-Pan-60 min significantly reduced cell viability of ovarian and liver cancer cells by 14.5 (500 µg/mL) and 17% (1000 µg/mL), respectively (P < 0.05). The protective effect against oxidative stress on H2O2-stressed HaCaT cells was obtained with H-Pep-60 min, which reduced 25% of ROS at 250 µg/mL (P < 0.05). The findings demonstrate the safe use of green biomass as a source of plant protein hydrolysates. [ABSTRACT FROM AUTHOR]

Objective: miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets. Results: In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC. [ABSTRACT FROM AUTHOR]

The ectopic expression of cellular retinoic acid binding protein 2 (CRABP2) is associated with various tumorigenesis. However, the effects of CRABP2 on the progression of cervical cancer are still unclear. The current study aimed to investigate the role of CRABP2 in the malignant phenotypes of cervical cancer cells. CRABP2 was artificially regulated in CaSki, SiHa, and C-33A cells. CCK-8 assay and flow cytometry were used to assess the cell proliferation and apoptosis abilities, respectively. Wound healing assay and transwell assay were employed to measure the cell migration and invasion abilities, respectively. The results showed that CRABP2 was highly expressed in cervical carcinoma tissues and cell lines, and its high expression was associated with poor overall survival. Knockdown of CRABP2 promoted the cell apoptosis and inhibited cell proliferation, migration, and invasion in cervical carcinoma cells, whereas CRABP2 overexpression exhibited the opposite results. Mechanically, CRABP2 silencing suppressed the Integrin β1/FAK/ERK signaling via HuR. Treatment with siITGB1 or a FAK inhibitor PF-562271 or an ERK inhibitor FR180204 reversed the promoting effects of CRABP2 on cell proliferation, migration, and invasion. Moreover, the overexpression of CRABP2 reverted the HPV16 E6/E7 knockdown-induced inhibition of cell proliferation, migration, and invasion in cervical cancer cells. These results suggested that HPV16 E6/E7 promoted the malignant phenotypes of cervical cancer by upregulating the expression of CRABP2. In conclusion, CRABP2, upregulated by HPV E6/E7, promoted the progression of cervical cancer through activating the Integrin β1/FAK/ERK signaling pathway via HuR. [ABSTRACT FROM AUTHOR]

Background: Globally, the fourth most prevalent type of cancer among women is carcinoma cervix. Self-sampling is a secure and simple method that makes it easier to contact women who would not otherwise take part in a clinician-based screening or make a screening test more accessible to them. This study aims aim to assess the degree to which the self-sampling method has reduced the discomfort and barriers towards cervical cancer screening and to determine if the development of more patient-centered screening programs can improve screening participation rates and reduce the incidence of cervical cancer. Methodology: This is a cross sectional study that was conducted at a tertiary care hospital in South India. The study involved female employees working at the PSG Institute of Medical Sciences and Research, Coimbatore in South India. There were around 1284 females employed in this institution who were above 30 years of age. This research study was carried out over the period between May 2021 to April 2022. Verbal consent was obtained at the start of the interview. The questionnaire consisted of socio-demographic details such as age, educational status, occupation, and questions regarding their previous screening history and reasons for not having done a pap smear in the past. The collected data were entered into Epidata version 3.1, and subsequent data analysis was conducted using STATA version 12.0. Results: Out of 1284 female employees in the age group of 30-65 years working in the tertiary care institution, only 200 women participated in the self-sampling camp conducted in the institution premises. The participation rate was 15.5%. Among those who participated, 177 (88.5%) women responded to the phone call, while 23 (11.5%) women did not answer the phone call. Despite pap smear being part of the annual health checkup for all employees done free of cost, only 45 women (25.4%) had previous pap screening tests. 23(13%) women were from the age group of 46-55 years. The swab provided to take the sample was felt easy to use by most of the people in all the age groups (97%) and the p-value was significant (P=0.007).49.1% women said that they would opt for self-screening while 24.8% expressed their preference to visit clinician to take the sample. 25.9% of women were not able to decide at the moment. Conclusion: Self-sampling helps to overcome the obstacles and barriers and increases the screening participation rates. [ABSTRACT FROM AUTHOR]

Introduction: Cervical carcinoma is the second commonest malignancy among females worldwide. In India, about 365.71 million women aged over 15 years are more vulnerable to cervical carcinoma. Risk factors may include immunodeficiency diseases, herpes, smoking and oral contraceptives. Scientific literature has documented that type 2 diabetes mellitus (T2DM) could aggravate the risk of some malignancies (hepatic, pancreatic, endometrial). This study aimed to evaluate the potential association between cervical carcinoma and diabetes mellitus in women. Material and Methods: Patients with cervical carcinoma, with or without diabetes, were assigned to two groups based on attainment of menopause. SPSS version 11.5 was used for data analysis. Odds ratios were calculated, and the chi-square test was used. P-values ≤ 0.05 were considered statistically significant. Results: It was observed that 29% of patients with cervical cancer were sixty to seventy years old, with a majority (40%) of them being multiparous. Though the association of body mass index as a risk factor for diabetic patients with cervical carcinoma was not significant in pre-and post-menopausal age groups, T2DM in cervical carcinoma is a useful prognostic indicator. Conclusions: Diabetic females after attaining menopause have a higher risk of developing cervical carcinoma and therefore should mandatorily receive routine screening. Future research with a longer timeframe is needed in order to generalize the results. [ABSTRACT FROM AUTHOR]

–The parent nuclear structure of piperine served as the basis for the design and synthesis of thirteen derivatives through nucleophilic substitution method. These derivatives were subsequently characterized by 1H NMR, 13C NMR, and HR-MS analysis. The antiproliferative activities of these compounds against 293T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines were assessed through the MTT assay. Compound 4b exhibited remarkable antiproliferative activity against Hela cells (IC50 = 1.80 μM), surpassing that of both 5-fluorouracil (IC50 = 44.58 μM) and piperine itself. Furthermore, subsequent investigations revealed that compound 4b displayed significant anti-proliferation, anti-migration and anti-invasion effects on Hela cells. These findings suggest that compound 4b may be a promising lead compound for the treatment of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between the DNA methylation state of NRG1 promoter and its expression changes, and to analyze the clinical significance of its regulatory mechanism of DNA methylation in cervical carcinoma. Methods: This was a retrospective study. One-hundred and twenty patients from the Department of Gynecology of Cangzhou People's Hospital from September 2017 to September 2019 were selected, including 40 cases of cervical SCC, 40 cases of high grade squamous intraepithelial lesions (HSIL) and 40 cases of control cervical tissues. RT-qPCR, immunohistochemistry and DNA methylation-specific PCR (MSP) were used to detect the mRNA and protein expression of NRG1 and DNA methylation status in different tissue types. Results: Immunohistochemical results showed that the positive protein expression rate of NRG1 gene in the SCC group was lower than that in both HSIL and Control groups. RT-qPCR results showed that the mRNA gene of NRG1 gradually decreased in expression with the increase of cervical tissue lesions, with a statistically significant difference. Similarly, it also found that the mRNA expression level of NRG1 in the SCC group was independent of patients' age (p>0.05), but significantly correlated with tumor pathological staging, surgical pathology staging and lymphatic metastasis (p<0.05). Furthermore, methylation-specific PCR results revealed a significantly higher DNA methylation rate of NRG1 gene in the SCC group than in both HSIL and Control groups, with a statistically significant difference. Moreover, the methylation degree of NRG1 gene in SCC tissues was negatively correlated with its mRNA expression (p<0.05). Conclusions: Abnormal DNA hypermethylation of NRG1 gene inhibits the expression of mRNA and protein in the progression of cervical tissue from normal to cancerous state, which is involved in the occurrence and development of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization states that cervical carcinoma is the fourth most common cancer among women worldwide. Pap smear is the simplest and easiest test to detect this prevalent cancer at its nascent stages. Aims and Objectives: This study aims to evaluate Pap smears using the conventional method (Bethesda 2014) and correlate the abnormal smears with cervical biopsy. Materials and Methods: The study is a combined retrospective and prospective study, from January 2021 to August 2023. Pap smears received were evaluated according to Bethesda 2014. Those cases categorized as Epithelial Cell Abnormality (ECA), were correlated with corresponding histopathology on cervical biopsy. Results: Out of the 615 pap smears in this study, 525 cases (91%) were categorized as Negative for Intraepithelial Lesion or Malignancy, 53 cases (9%) as Epithelial Cell Abnormality, and 37 cases (6%) as unsatisfactory. In the Negative for Intraepithelial Lesion or Malignancy category, 353 cases (67.2%) were reactive cellular changes including inflammation, four cases (0.7%) were squamous metaplasia, and 24 cases (4.6%) were atrophic smears. In the ECA category–21 cases (39.6%) were Atypical squamous cells of undetermined significance, two cases (3.8%) were Low-grade squamous intraepithelial lesion, five cases (9.4%) were Atypical squamous cells-cannot exclude HSIL(ASC-H), 14 cases (26.4%) were High grade squamous intraepithelial lesion (HSIL) and 3 cases (5.6%) were squamous cell carcinoma (SCC) cervix, seven cases were of ECA-glandular type (13.2%). On histopathological correlation, the maximum correlation was found for HSIL and SCC cases, 71% and 100%, respectively. Conclusion: Pap smear is a crucial screening tool to diagnose cervical carcinoma at its nascent stage. This study showed a positive correlation for high-grade lesions on Pap smears.

Background: Angiogenesis is necessary for invasion and metastasis of cervical carcinoma and is a crucial stage in controlling the course of malignancy. Microvasculature may be quantified by calculating Mean Microvessel Density (MVD) using CD31 Immunohistochemical (IHC) labeling of endothelial cells. E6 and E7 oncogenes of Human Papillomavirus (HPV) will inactivate p53 and pRb, respectively. This has been discovered to encourage angiogenesis by up-regulating vascular endothelial growth factor and down-regulating thrombospondin-1 during the early stages of carcinogenesis. Aim and Objectives: To assess the IHC expression of CD31 in cervical dysplasia and carcinomas and link these expressions with the IHC expression of HPV (16E6 + 18E6) and specific clinicopathological criteria, such as stage and grade of cervical carcinoma. Material and Methods: In a cross-sectional investigation, 52 cervical tissue samples were formalin-fixed and paraffin-embedded. On hematoxylin and eosin slides, the histological diagnoses were obtained. Samples were then stained immunohistochemically with monoclonal mouse antibodies, including anti-CD31 antibody and Anti-HPV (16E6 + 18E8) antibody. Results: Mean MVD rose significantly with increasing cervical lesion severity. In 78.1% of patients with invasive cervical carcinomas, HPV expression was detected, compared to 41.7% of cases with high-grade squamous intra-epithelial lesion and 37.5% of cases with low-grade squamous intra-epithelial lesion. Conclusion: HPV plays a crucial role in malignant transformation of the cervix, with a substantial positive association between a rise in MVD and expression of high-risk HPV types (16 and 18) in malignant and premalignant instances.

Background: Immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 antibodies, have emerged as promising therapeutic options for cervical cancer. However, the efficacy of anti-PD-1 antibody monotherapy is limited. Cryoablation could elicit an anti-tumor immune response, thereby presenting itself as a potential approach to augment the response of ICIs. The aim of our study was to investigate the systemic immunological effects of cryoablation and the potential synergistic anti-tumor effects of cryoablation and anti-PD-1 antibody in cervical cancer. Methods: We established U14 murine bilateral subcutaneous cervical cancer model, wherein the primary tumors were treated with cryoablation. Flow cytometry, immunohistochemistry and RNA-seq were used to analyze the immune cell infiltration and immune-associated pathways in the secondary tumor. Results: Our study revealed that cryoablation reprogrammed the immune landscape, leading to an enhanced infiltration of CD8+ T cell in distant tumors. Cryoablation created a conducive environment for increasing the efficacy of anti-PD-1 immunotherapy. Cryoablation in combination with anti-PD-1 antibody inhibited distant tumors growth and improved mouse survival. Mechanistically, this combination therapy could augment the infiltration of CD8+ T cells, CD4+ T cells, dendritic cells and M1-like tumor-associated macrophages, enhance multiple aspects of antitumor immune response, and reduce immunosuppressive cells such as M2-like tumor-associated macrophages and myeloid-derived suppressor cells in distant tumors. Conclusions: Combination therapy with cryoablation and anti-PD-1 antibody induces an effective abscopal effect in murine model of cervical cancer and may be a novel therapeutic approach for patients with advanced/recurrent cervical cancer.

Background: The World Health Organization states that cervical carcinoma is the fourth most common cancer among women worldwide. Pap smear is the simplest and easiest test to detect this prevalent cancer at its nascent stages. Aims and Objectives: This study aims to evaluate Pap smears using the conventional method (Bethesda 2014) and correlate the abnormal smears with cervical biopsy. Materials and Methods: The study is a combined retrospective and prospective study, from January 2021 to August 2023. Pap smears received were evaluated according to Bethesda 2014. Those cases categorized as Epithelial Cell Abnormality (ECA), were correlated with corresponding histopathology on cervical biopsy. Results: Out of the 615 pap smears in this study, 525 cases (91%) were categorized as Negative for Intraepithelial Lesion or Malignancy, 53 cases (9%) as Epithelial Cell Abnormality, and 37 cases (6%) as unsatisfactory. In the Negative for Intraepithelial Lesion or Malignancy category, 353 cases (67.2%) were reactive cellular changes including inflammation, four cases (0.7%) were squamous metaplasia, and 24 cases (4.6%) were atrophic smears. In the ECA category-21 cases (39.6%) were Atypical squamous cells of undetermined significance, two cases (3.8%) were Low-grade squamous intraepithelial lesion, five cases (9.4%) were Atypical squamous cells-cannot exclude HSIL(ASC-H), 14 cases (26.4%) were High grade squamous intraepithelial lesion (HSIL) and 3 cases (5.6%) were squamous cell carcinoma (SCC) cervix, seven cases were of ECA-glandular type (13.2%). On histopathological correlation, the maximum correlation was found for HSIL and SCC cases, 71% and 100%, respectively. Conclusion: Pap smear is a crucial screening tool to diagnose cervical carcinoma at its nascent stage. This study showed a positive correlation for high-grade lesions on Pap smears. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is necessary for invasion and metastasis of cervical carcinoma and is a crucial stage in controlling the course of malignancy. Microvasculature may be quantified by calculating Mean Microvessel Density (MVD) using CD31 Immunohistochemical (IHC) labeling of endothelial cells. E6 and E7 oncogenes of Human Papillomavirus (HPV) will inactivate p53 and pRb, respectively. This has been discovered to encourage angiogenesis by up-regulating vascular endothelial growth factor and down-regulating thrombospondin-1 during the early stages of carcinogenesis. Aim and Objectives: To assess the IHC expression of CD31 in cervical dysplasia and carcinomas and link these expressions with the IHC expression of HPV (16E6 + 18E6) and specific clinicopathological criteria, such as stage and grade of cervical carcinoma. Material and Methods: In a cross-sectional investigation, 52 cervical tissue samples were formalin-fixed and paraffin-embedded. On hematoxylin and eosin slides, the histological diagnoses were obtained. Samples were then stained immunohistochemically with monoclonal mouse antibodies, including anti-CD31 antibody and Anti-HPV (16E6 + 18E8) antibody. Results: Mean MVD rose significantly with increasing cervical lesion severity. In 78.1% of patients with invasive cervical carcinomas, HPV expression was detected, compared to 41.7% of cases with high-grade squamous intra-epithelial lesion and 37.5% of cases with low-grade squamous intra-epithelial lesion. Conclusion: HPV plays a crucial role in malignant transformation of the cervix, with a substantial positive association between a rise in MVD and expression of high-risk HPV types (16 and 18) in malignant and premalignant instances. [ABSTRACT FROM AUTHOR]

Cervical cancer is one of the leading causes of cancer death among females, worldwide. The contributory role of different cellular pathways in the process of carcinogenesis is still poorly understood. Our study was focused here to understand the functional evaluation of key regulatory genes of FA-BRCA pathway in the development of CACX and their role in chemo-tolerance of the disease by analyzing the molecular profile of the genes both in normal and tumour tissue of our sample pool, also validated in in silico datasets. Later on, prognostic importance of the genes was further evaluated in plasma DNA and cisplatin-treated in vitro system. We found that expression profile of FA-BRCA pathway genes was gradually reduced from undifferentiated basal-parabasal layers of normal tissue towards the progression of the disease. Further analysis revealed that frequent promoter methylation [32–55%] and deletion [34–52%] events were the plausible reasons for their reduced expression in CACX. Noticeably, invasion of promoter methylation of the genes [11–17%] in plasma CTCs of CACX patients was positively correlated [p < 0.001] with poor prognosis among patients. On the other hand, functional upregulation of these genes at higher concentrations [IC50–70] of cisplatin was a predictor for the development of drug tolerance, as evaluated in our in vitro study. This finding was supported further by low prevalence of γ-H2X foci formation and reduced expression of DNMT1 at higher concentrations of cisplatin. In totality, we discovered that the FA-BRCA pathway must be inactivated for cancer formation. In contrast, elevated gene expression played a substantial role in building of chemo-tolerance and might be associated with developing increased risk of disease recurrence among patients. Schematic diagram illustrating the gradual changes in the molecular profile of FA-BRCA pathway genes from different layers of normal epithelium towards the disease development and its role in development of chemo-tolerance of the disease [ABSTRACT FROM AUTHOR]

Squamous cervical carcinoma (SCC) requires particular attention in diagnostic and clinical management. New diagnostic tools, such as (positron emission tomography–magnetic resonance imaging) PET–MRI, consent to ameliorate clinical staging accuracy. The availability of new technologies in radiation therapy permits to deliver higher dose lowering toxicities. In this clinical scenario, new surgical concepts could aid in general management. Lastly, new targeted therapies and immunotherapy will have more room in this setting. The aim of this narrative review is to focus both on clinical management and new therapies in the precision radiotherapy era. [ABSTRACT FROM AUTHOR]

Background: To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. Methods: The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. Results: We found that Valyl-Glutamate, N, N′-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. Conclusions: This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.

Lymphoepithelioma-like carcinoma of the cervix (LELC) is a rare subtype of squamous cell carcinoma. This is a case report of a 40-year-old female patient diagnosed with LELC. The tumor is clinically presented as an exophytic mass on the front lip of the cervix. Magnetic resonance imaging (MRI) of the pelvis revealed a cervical tumor mass with a diameter of 21 mm. The findings of the preoperative pathohistological analysis of the biopsy tissue indicated LELC. The disease was clinically and radiologically staged as IB1 stage according to the 2009 FIGO classification, and the patient underwent surgical treatment. A total radical hysterectomy with pelvic lymphadenectomy was performed, followed by external beam radiotherapy. The patient was regularly monitored with the last check-up on February 2024 (36 months) and MRI control of the pelvis and abdomen without signs of recurrence of the underlying disease. The patient is in good general condition, without subjective complaints and side effects of the applied therapy.

We aimed to explore the diagnostic value of multi-slice spiral computed tomography dynamic enhanced scanning (MSCT) for the lymph node metastasis of cervical cancer and the causes for missed diagnosis. A total of 283 patients with cervical cancer treated from March 2019 to March 2022 were selected. Lymph node metastasis was observed by MSCT. The results were compared with those of surgical and pathological examinations to analyze the diagnostic value of MSCT. The patients with confirmed lymph node metastasis were divided into a missed diagnosis group (n = 41) and a nonmissed diagnosis group (n = 128). The factors for missed diagnosis by MSCT were explored by multivariate logistic regression analysis. A back propagation (BP) neural network model was constructed and evaluated. Results: The positive coincidence rate of MSCT diagnosis was 92.75%, the negative coincidence rate was 71.72%, and the total coincidence rate was 81.98%. The area under the receiver operator characteristic curve of MSCT was 0.741 (95% confidence interval: 0.723-0.826), indicating a high diagnostic value. A high degree of differentiation, negative Ki-67 expression, and interstitial infiltration depth of

To investigate the value of amide proton transfer weighted (APTw) combined with diffusion kurtosis imaging (DKI) in quantitative prediction of lymph node metastasis (LNM) in cervical carcinoma (CC). Data of 19 LNM(+) and 50 LNM(−) patients with CC were retrospectively analyzed. 3.0 T MRI scan was performed before the operation, including APTw and DKI. After post-processing, quantitative magnetization transfer ratio asymmetric at 3.5 ppm [MTRasym (3.5 ppm)], mean kurtosis (MK), and mean diffusivity (MD) maps were obtained. The MTRasym(3.5 ppm), MK, and MD values were respectively measured by two observers, and intra-class correlation coefficients (ICC) were used to test the consistency of the results. The independent samples t -test or Mann-Whitney U test was used to compare the differences in the values of each parameter. The ROC curve was used to analyze the predictive performance of parameters with significant differences and their combination parameter. The two observers had good agreement in the measurement of each data (ICC > 0.75). The MTRasym(3.5 ppm) and MK values of the LNM(+) group(3.260 ± 0.538% and 0.531 ± 0.202) were higher than those of the LNM(−) group(2.698 ± 0.597% and 0.401 ± 0.148) (P < 0.05), while there was no significant difference in MD values between the two groups (P > 0.05). The area under the curves (AUCs) of MTRasym(3.5 ppm), MK value, and MTRasym(3.5 ppm) + MK value were 0.763, 0.716, and 0.813, respectively, when predicting LNM status of CC. APTw and DKI can quantitatively predict LNM status of CC, which is of importance in clinical diagnosis and treatment. • APT weighted imaging is a novel molecular MR imaging method based on the chemical exchange saturation transfer mechanism. • DKI is a MR imaging that directly estimates and quantifies the non-Gaussian nature of water molecule diffusion in the body. • Our study shows that APT weighted imaging and DKI can quantitatively predict LNM status of CC. [ABSTRACT FROM AUTHOR]

Aim: At present, COBAS human papillomavirus (HPV) and Aptima HPV screening are widely used to detect HPV infection. In this study, we compared and analyzed the positive rates of DNA and mRNA (n = 10,128 women). Methods: After HPV screening, colposcopy was performed. Subsequently, pathological analysis was conducted on the screening results. Results: In Aptima HPV 16 group, the proportion of pathological lesions ≥CIN2 was 32.69%, while in COBAS HPV group, it was 24.18% (p < 0.05). Aptima HPV other risk types and COBAS HPV other risk types, the proportion of cases ≥CIN2 was 12.42 and 5.79%, respectively (p < 0.001). Conclusion: The results illustrated that the Aptima HPV test detects more accurately clinically relevant lesions than the COBAS test. The aim of this study was to evaluate the analysis of the application value of HPV based on RNA and DNA detection in early screening of cervical lesions. In the Aptima HPV 16 group, the proportion of pathological lesions ≥CIN2 level was 32.69%, while in the COBAS HPV group, this proportion was 24.18% (Chi-square test, χ2 = 6.135; p < 0.05). There was no difference in pathological test results (≥CIN2) level between Aptima HPV 18/45 and COBAS HPV 18 positive cases. Aptima HPV other risk types and COBAS HPV other risk types, the proportion of cases with ≥CIN2 level was 12.42 and 5.79%, respectively (Chi-square test, χ2 = 35.68; p < 0.001). Aptima HPV has better accuracy in early screening of cervical cancer. [ABSTRACT FROM AUTHOR]

Background: Treatment of metastatic cervical cancer is a tricky issue. Currently, the National Comprehensive Cancer Network (NCCN) guideline recommends chemotherapy combined with bevacizumab for recurrent or metastatic cervical cancer. Still, the recurrence rate is high and the survival rate is low after standard treatment. We urgently need to achieve a multimodal therapy approach for recurrent or metastatic cervical cancer. Case description: We report the case of a patient with stage IB2 cervical squamous carcinoma who developed multiple metastases within a short term after receiving first-line standard treatment, and she underwent interstitial brachytherapy after systemic therapy with an encouraging outcome. The patient developed suspected inguinal lymph node metastases after 9 months at the end of first-line therapy and multiple metastases in the inguinal lymph nodes, anterior abdominal wall, and right lung after 17 months. As the patient had residual inguinal lymph nodes after systemic therapy, she received 3D-printed template-guided interstitial brachytherapy to the inguinal lymph nodes and maintenance therapy. By Sep 2023, she had achieved a good treatment outcome with a progression-free survival (PFS) of 36 months. Conclusion: Based on our patient response, when multiple metastases develop in the short term in early-stage cervical squamous carcinoma after first-line therapy, we may consider implementing local therapy combined with systemic therapy. [ABSTRACT FROM AUTHOR]

Background: Cervical carcinoma is a type of malignant tumor that primarily develops in the cervix, the lower part of the uterus. In recent years, Despite the considerable progress made in immunotherapy research for cervical carcinoma, an important aspect has been largely overlooked - the absence of a comprehensive bibliometric analysis in this field. By employing bibliometric techniques, this study aims to fill this gap and provide a comprehensive overview of the knowledge structure and research hotspots within the realm of immunotherapy in cervical carcinoma. Method: A comprehensive search was conducted on the web of science core collection(WoSCC) database to identify publications related to immunotherapy specifically for the treatment of cervical carcinoma. The search spanned the period from the year 2000 to 2023. Several analytical tools were employed. These included VOSviewers, CiteSpace, and the R package "bibliometrix". Results: A total of 654 research articles from 66 different countries have been included in the analysis. The United States and China have emerged as the leading countries in publishing research on immunotherapy in cervical carcinoma. Leiden University and Memorial Sloan-Kettering Cancer Center from the Netherlands and the United States respectively have a close cooperation. Fudan University from China and the German Cancer Research Center are also among the key institutions leading research in this area. Frontiers in Oncology has emerged as the most popular and widely recognized publication in the field of immunotherapy in cervical carcinoma. Journal of Clinical Oncology is frequently cited by researchers in this area. Van Der Burg, Sjoerd H has published the highest number of papers. Tewari, Krishnansu S has been the most co-cited author. Keywords such as PD-L1, chemotherapy, and immune checkpoint inhibitors have gained significant attention in recent years. Conclusion: This is the first bibliometric study that comprehensively summarizes the research trends and developments of immunotherapy in cervical carcinoma. This groundbreaking study not only summarizes the current research trends and developments in immunotherapy for cervical carcinoma but also provides a reference for scholars studying the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells. Methods The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells. Results In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT. Conclusion LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer.

Jie Dai,1,&ast; Shao Zhang,2,&ast; Yuhan Shi,3 Jinmei Xu,2 Weipeng Liu,1 Jia Yang,1 Li Shi,1 Zhiling Yan,2,4 Chuanyin Li1 1Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China; 2Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China; 3College of Agronomy and Biotechnology, Yunnan Agricultural University, Kunming, 650041, People’s Republic of China; 4Department of Gynaecologic Oncology, The Hospital of Yuanmou, Yuanmou, 651300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiling Yan, Department of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, 650118, People’s Republic of China, Email yanzhiling2021@126.com Chuanyin Li, Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, 650118, People’s Republic of China, Email chuanyinli@imbcams.com.cnBackground: Long noncoding RNAs (LncRNAs) have been revealed to involve in cervical cancer (CC) developing. The current study was designed to explore the association of SNPs (rs217727, rs2366152, rs1859168, rs10505477) located in the lncRNA H19, HOTAIR, HOTTIP and CASC8 genes with the risk of CC in a Chinese Han population.Methods: Four SNPs were selected and genotyped in 1426 participants (274 CIN patients, 448 CC patients, and 704 healthy control individuals) using MassArray. The association of these SNPs with susceptibility to CC was evaluated.Results: Significant differences in allelic distribution of rs217727 were observed in the comparison of CC with control (P = 0.001), indicating the risk of rs217727-A allele in CC (OR = 1.33; 95% CI: 1.12– 1.58). The inheritance model analysis revealed that 2AA+GA genotype represented a certain risk of CC (P = 0.001, OR = 1.35; 95% CI: 1.13– 1.62). The stratified analysis revealed a risk of the rs217727-A allele for cervical squamous cell carcinoma (SCC) (P = 0.002, OR = 1.33; 95% CI: 1.11– 1.60).Conclusion: rs217727 in lncRNA H19 exhibited a significant correlation with CC susceptibility, particularly SCC, and A/A genotype of this SNP might present as a risk in CC.Keywords: cervical cancer, lncRNA, H19, association, SNPs, CC, long noncoding RNAs

Background and Objectives: This study aimed to evaluate the tumor response relating to and survival benefit of transarterial chemoperfusion (TACP) and transarterial chemoembolization (TACE) in the treatment of patients with unresectable gynecologic tumors who are intolerant of or have a suboptimal response to chemotherapy and radiotherapy. Materials and Methods: Between January 2000 and October 2023, 75 patients diagnosed with gynecologic tumors underwent 213 TACP and 154 TACE procedures. Of these, 33 patients were treated with TACP, 20 were treated with TACE, and 22 received a combination of both therapies. A retrospective evaluation of local tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) was conducted, and survival rates were determined using the Kaplan–Meier estimator. Results: Of the total 75 patients, 50 (67%) maintained a stable course of disease until the completion of therapy, 10 (13%) had a partial response, 2 (3%) had a complete response following thermal ablation, and 13 (17%) experienced progression. Furthermore, a 6% reduction in the sum of the longest diameters and an 8% reduction in tumor volume were observed. The median overall survival was 16.15 months, while the median progression-free survival was 13.19 months. Conclusions: TACP and TACE are potential treatment options for local tumor control in patients with unresectable gynecologic tumors who are intolerant of or show a poor response to chemotherapy and radiotherapy. However, further investigation and adjustment of treatment protocols are required to improve therapy response and survival outcomes.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are becoming more common in younger women. Solute carrier family 39 member 4 (SLC39A4) produces a zinc ion transporter involved in metastasis and invasion of tumors. Methods: The Cancer Genome Atlas RNA-seq data was used to investigate the expression of SLC39A4 and its prognostic potential. The assessment of the effect of SLC39A4 on cell growth and migration in CESC was conducted using MTT, colony formation, and Transwell assays. SLC39A4 was studied in vivo using a xenograft mouse model, and its functional involvement in oncogenesis was investigated by identifying the associated differentially expressed genes (DEGs). We evaluated the relationships among SLC39A4 levels, chemosensitivity, radiosensitivity and immune infiltration. Results: SLC39A4 was upregulated in CESC samples, and individuals with greater SLC39A4 mRNA expression had shorter overall survival. SLC39A4 has been identified to be a regulator of tumor cell metastasis and proliferation in vivo and in vitro, with an area under the curve of 0.874 for diagnosing CESC. In total, 948 DEGs were discovered to be enriched in key CESC progression-related signaling pathways. Additionally, intratumoral immune checkpoint and infiltration activity were associated with SLC39A4 expression. High SLC39A4 expression exhibited poor chemosensitivity and radiosensitivity profiles. Conclusion: In conclusion, SLC39A4 is a key regulator of CESC development, prognosis, and the composition of the tumor immune microenvironment. SLC39A4 could be used as a prognostic or diagnostic screening tool and as a potential target for CESC treatment.

Background: Cervical cancer (CC) is currently the most common malignant tumour in the female reproductive tract, and paclitaxel (PTX) is a commonly used chemotherapeutic agent, but tumour cell resistance will seriously affect the therapeutic efficacy of PTX. Nanoparticle human serum albumin-bound paclitaxel (Nano-HSA-PTX) is a novel drug delivery modality that may have superior effects to PTX alone. Objective: To clarify the effect of Nano-HSA-PTX on cervical carcinoma (CC) cells and the underlying mechanisms. Methods: After the preparation of Nano-HSA-PTX, its morphology was observed by electron transmission microscope (TEM), and its entrapment efficiency (EE%) and drug loading rate (DL%) were detected. Nano-HSA-PTX was compared with conventional PTX for drug metabolism. Additionally, CC HeLa and SiHa cells were purchased and divided into three groups to treat with Nano-HSA-PTX, PTX and normal saline, respectively. MTT, cell cloning, Transwell and cell scratch assays were carried out to determine cell proliferation, invasion and migration, flow cytometry and Western blotting were performed to detect apoptosis rate and apoptosis-related protein expression, and PCR was conducted to quantify oxidative damage indicators. Further, CYP3A4 and CYP2C8 expression patterns in CC cells (HeLa and SiHa) and human normal cervical epithelia (End1/E6E7) and the changes of their levels under the intervention of Nano-HSA-PTX were measured. Subsequently, C57BL/6mice were purchased for subcutaneous tumorigenesis experiment to observe the impact of Nano-HSA-PTX on tumor growth. Results: Under TEM, Nano-HSA-PTX was complete and arranged compactly, with a stable structure and markedly higher EE% and DL% than PTX (P

Background: Posterior reversible encephalopathy syndrome (PRES), a neurological disorder with an unknown aetiology, is characterised by visual impairment, headache, vomiting, seizures, and transient alterations in consciousness. Case report: We present the case of a 49-year-old woman with advanced cervical carcinoma who received second-line therapy with oral anlotinib (12 mg, days 1-14, every 21 days) and injectable tislelizumab (200 mg, day 1, every 21 days). After 7 days of anlotinib administration, she began experiencing symptoms suggestive of PRES and was diagnosed on day 11. Interruption of anlotinib and supportive treatment led to recovery of her binocular vision. The Naranjo score (+5) graded the causality of this reaction as probable, suggesting the possibility that the event may have been an adverse reaction to anlotinib. Ethics: This case report was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (Reference no. K-2023-068, 2023/06/09). Informed consent was obtained from the patient and her family. [ABSTRACT FROM AUTHOR]

The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma. Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma. What is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma. [ABSTRACT FROM AUTHOR]

Lipase G, endothelial type (LIPG) is expressed abundantly in tissues with a high metabolic rate and vascularisation. Research on LIPG has focussed on metabolic syndromes. However, the role of LIPG in providing lipid precursors suggests that it might function in the metabolism of carcinoma cells. Analysis in The Cancer Genome Atlas indicated that patients with cervical carcinoma with high LIPG expression had a lower survival prognosis compared with patients with low LIPG expression. The mechanism underlying the effects of LIPG in cervical carcinoma is unclear. The present study aimed to determine the role of LIPG in cervical carcinoma and its mechanism. The results showed that the LIPG expression level was higher in cervical cancer. Downregulation of LIPG expression inhibited cell migration, invasion, proliferation, and the formation of cell colonies, but increased the rate of apoptosis. The Human papillomavirus E6 protein might reduce the expression of miR-148a-3p, relieve the inhibitory effect of miR-148a-3p on LIPG expression, and promote the progression of cervical cancer through the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signalling pathway. What is already known on this subject? LIPG provides lipid precursors, suggesting that it might function in the metabolism of carcinoma cells What do the results of this study add? LIPG might be regulated by HPV16 E6/miR-148a-3p and promote cervical carcinoma progression via the PI3K/AKT/mTOR signalling pathway. What are the implications of these finding for clinical practice and/or further research? The results indicated that novel treatment and diagnosis strategies for cervical carcinoma could be developed related to LIPG. However, the detailed relationship between LIPG and cervical carcinoma remains to be fully determined. [ABSTRACT FROM AUTHOR]

We focus on hsa_circ_0084912's role in Cervical cancer (CC) and its molecular pathways. In order to determine the expression of Hsa_circ_0084912, miR-429, and SOX2 in CC tissues and cells, Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized. Cell counting kit 8 (CCK-8), colony formation and Transwell assays were respectively to analyze CC cell proliferation viability, clone formation ability and migration. RNA immunoprecipitation (RIP) assay and dual-luciferase assay were used to assure the targeting correlation among hsa_circ_0084912/SOX2 and miR-429. By using a xenograft tumor model, the hsa_circ_0084912 impact on CC cell proliferation in vivo was confirmed. Hsa_circ_0084912 and SOX2 expressions were aggrandized, however, miR-429 expression was descended in CC tissues and cells. Silencing hsa_circ_0084912 inhibited cell proliferation, colony formation and migration in vitro of CC, meanwhile reducing growth of tumor in vivo. MiR-429 might be sponged by Hsa_circ_0084912 to control SOX2 expression. Hsa_circ_0084912 knockdown impact on the malignant phenotypes of CC cells was restored by miR-429 inhibitor. Moreover, SOX2 silencing eliminated the promotive effects of miR-429 inhibitors on CC cell malignancies. By raising SOX2 expression by targeting miR-429, hsa_circ_0084912 accelerated the development of CC, offering fresh proof that it is a viable target for CC treatment. [ABSTRACT FROM AUTHOR]

Background: The roles of low molecular mass polypeptide 2 (LMP2) and transporter-associated with antigen processing (TAP2) in tumorigenesis are controversial. Here we aimed to explore the effect of LMP2 and TAP2 on the oncogenesis and metastasis of cervical cancer cells. Methods: The expressions of LMP2 and TAP2 in cervical cancer and normal tissues were determined by qPCR. Plate colony formation, cell counting kit-8 analysis and in vivo tumor xenograft assays were used to detect the tumor growth. Wound healing and transwell assays were used to detect the metastasis of cervical cancer. Gelatin zymography and western blotting assays were used to detect the effect of LMP2 and TAP2 on the EMT and Wnt/β-catenin pathway in cervical cancer cells. Results: In the present study, we reported that LMP2 and TAP2 levels were overexpressed in cervical cancer. Overexpression of LMP2 and TAP2 impaired the proliferation of Hela cells. In vivo studies substantiated that LMP2 and TAP2 antagonized tumor growth. Likewise, LMP2 and TAP2 overexpression decreased the migration and invasion ability of Hela cells by regulating the process of epithelial-mesenchymal transition (EMT). Mechanically, LMP2 and TAP2 subverted the protein abundance of Wnt1 and β-catenin, thereby downregulating their downstream targets Cyclin D1 and c-Myc. In addition, Wnt1 overexpression partially rescued the observed consequences of ectopic expression of LMP2 and TAP2 in cervical cancer cells. Taken together, our study revealed that LMP2 and TAP2 suppress the oncogenesis and metastasis of cervical cancer cells by Wnt/β-catenin pathway and altering EMT. Conclusion: LMP2 and TAP2 may inhibit the oncogenesis and metastasis of cervical cancer cells by inhibiting the process of EMT and the Wnt/β-catenin signaling pathway, which may provide important insight into prospective targets for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

Introduction: WHO has recommended global action to eliminate cervical cancer by the 21st century. HIV-infected women are at increased risk of acquiring HPV infection, progressing to pre-invasive, and invasive cervical cancers. Objectives: The objective was to assess the frequency of and the risk factors for pap smears abnormalities in HIV-seropositive and HIV-seronegative women. Materials and methods: This retrospective case control study conducted in a Medical College Hospital from January 2016 to December 2019 included case records of 330 married women aged more than 19 years. About 270 participants were eligible for controls and 60 for cases. Demographic details, CD4 count, and pap smear findings were noted, and statistical analysis was carried out. Results: Pap smear abnormalities were noted in 13.3% of HIV-infected women and 1.85% of HIV-negative women. The preponderance of inflammatory smear was 61.7% among seropositive women and 47% among seronegative women. The mean CD4 count among HIV-positive women was 534.34 ± 242.24 and in 64.14%, the CD4 count was >400. No statistically significant association between the abnormal pap smear results and the age of the individual, parity, and age at first intercourse was noted. Conclusion: Abnormal cervical cytology was seven times higher in HIV-infected women when compared with HIV-negative women and immunosuppression may be the predominant risk factor leading to cytological abnormalities in HIV-infected women. HIV-positive women showing inflammatory smears need further evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer is the fourth most common cancer in the world and the fourth leading cause of cancer death in women. In 2020, there were 604,000 new cases and 342,000 deaths from cervical cancer worldwide. Among these, non-squamous cell carcinoma accounts for about 20% of all cervical cancers and is increasing. It has long been known that non-squamous cervical cancer has a poorer prognosis than squamous cervical cancer. Reasons for this include relatively early lymph node metastasis and low sensitivity to radiotherapy. Therefore, chemotherapy is more likely to improve prognosis than radiotherapy. However, there are few studies on adenocarcinoma and a high level of evidence is not yet available. We have previously reported the efficacy of SOX (S-1+oxaliplatin) therapy for cervical adenocarcinoma in a pilot study. We report on a phase II trial of SOX therapy to evaluate its efficacy and safety. Recurrent non-squamous cell carcinoma (non-SCC) of the uterine cervix is resistant to treatment and has a poor prognosis. The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent non-SCC was examined in a phase II study. Fifteen patients were enrolled between August 2013 and March 2023. S-1 was administered orally at a daily dose of 80–120 mg for 14 days, and oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1. Each treatment cycle lasted 21 days. The anti-tumor effects, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. The median patient age was 54 (41–74) years. The anti-tumor effect was rated as a partial response in five patients, stable disease in four, and progressive disease in 6. The overall response rate was 33% and the disease control rate was 60%. Regarding hematologic toxicities of grade 3 or more severity, leukopenia, neutropenia, anemia, and thrombocytopenia occurred in 26.6–40.0%. None of the patients discontinued the treatment because of adverse events. The median PFS and OS were 6 months (95% confidence interval [CI]: 2–11 months) and 22 months (95% CI: 11–23 months), respectively. No treatment-related deaths occurred. These results suggest that SOX therapy is useful for the treatment of recurrent non-SCC with promising anti-tumor effects and minimal adverse events. [ABSTRACT FROM AUTHOR]

Background: Our aim was to assess the p16 expression in normal cervical epithelium and cervical lesions and how it correlated with HPV oncoprotein E7 and other etiological parameters of cervical cancer. Methods: For this purpose, we analyzed protein expression of p16 and E7 oncoprotein in total 20 normal cervical epithelium tissue (as control) and 62 cervical lesions. Next, the result was correlated with different clinico-pathological parameters. Results: Out of 62 cases of cervical lesions, we found around 75%–100% of the cervical lesion samples exhibited E7 nuclear protein expression, whereas around 33.33%–75% samples were p16 positive. On the other hand, p16 expression showed strong association with E7 oncoprotein and other clinico-pathological parameters (like high parity, early age of sextual debut) in the same set of samples of our study. Conclusion: We concluded that overexpression of p16 is very practical and can be readily implemented in most diagnostic pathology laboratories. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have revealed that primary tumor resection (PTR) surgery could improve prognosis in some solid tumors. Thus, we aimed to investigate whether patients with stage IVB cervical carcinoma can benefit from PTR surgery and who can benefit. Methods: We extracted and obtained data on patients with stage IVB cervical carcinoma from the SEER database from 2010 to 2017 and classified them into two groups: the surgery and the non-surgery group. The overall survival (OS) and cancer-specific survival (CSS) of the two groups were compared before and after propensity score matching (PSM). The independent prognostic variables were identified using univariate and multivariate Cox regression analyses. Then, the model was established to select the optimal patients to receive PTR surgery using multivariate logistic regression. Results: After PSM, the study included 476 cervical carcinoma (stage IVB) patients, of whom 238 underwent PTR surgery. Compared to the non-surgery group, the surgery group's median OS and median CSS were both longer (median OS: 27 months vs. 13 months, P < 0.001; median CSS: 52 months vs. 21 months, P < 0.001). The model showed no organ metastasis, adenocarcinoma, G1/2, and chemotherapy were more supportive of performing PTR surgery. The calibration curves and DCA showed that the model had high predictive accuracy and excellent clinical applicability. Finally, the "surgery benefit" group had the OS that was approximately four times better than "surgery non-benefit" group. Conclusion: PTR surgery can potentially improve the prognosis of patients with cervical carcinoma at stage IVB. The model could probably select optimal candidates and provide a new perspective on individualized treatment. [ABSTRACT FROM AUTHOR]

Abstract Cervical cancer, the fourth most common cancer among females in the world, ranks the second in China. In advanced disease, metastases may be commonly present in the lungs, bones, liver and lymph nodes or elsewhere, but uncommon to the skin. In this report, a 63‐year‐old woman was diagnosed as stage IVB cervical squamous cell cancer in January 2021. The patient was scheduled for concurrent chemoradiotherapy; however, a metastatic lesion of skin was proved by biopsy during the process of treatment. She died 1 month after confirmed skin metastases. Cutaneous metastasis of cervical cancer may predict the mix of lymphatic and hematogenous metastasis and the rapid fatal termination.

Background Untreated lymphedema of an extremity leads to an increase in volume. The therapy of this condition can be conservative or surgical. Methods “Lymphological liposculpture” is a two-part procedure consisting of resection and conservative follow-up treatment to achieve curative volume adjustment of the extremities in secondary lymphedema. This treatment significantly reduces the need for complex decongestive therapy (CDT). From 2005 to 2020, 3,184 patients with secondary lymphedema after breast cancer and gynecological tumors were treated in our practice and clinic. “Lymphological liposculpture” was applied to 65 patients, and the data were recorded and evaluated by means of perometry and questionnaires. Results The alignment of the sick to the healthy side was achieved in all patients. In 58.42% (n = 38), the CDT treatment could be completely stopped postoperatively; in another 33.82% (n = 22) of the patients, a permanent reduction of the CDT was achieved. In 7.69% (n = 5) patients, the postoperative CDT could not be reduced. A total of 92.30% (n = 60) of the patients described a lasting significant improvement in their quality of life. Conclusion “Lymphological liposculpture” is a standardized curative sustainable procedure for secondary lymphedema for volume adjustment of the extremities and reduction of postoperative CDT with eminent improvement of the quality of life.

Cervical cancer is a typical cancer characterized by abnormal cell growth in the cervical area. Ginkgo biloba L. is a deciduous tree of the genus Ginkgo, possessing anti-cancer effects. The aim of this study was to explore the effect of strain J1 from Ginkgo biloba L. on apoptosis of cervical cancer cells. Bacteriostatic activity test, MTT assay and Flow cytometry were used in this study. Crude extract of J1 fermentation reduced cell growth in cervical cancer. The crude extract of the fermentation broth of strain J1 had a good inhibitory effect on Staphylococcus aureus. The crude extract of the J1 fermentation had no toxic effect on normal WISH cells in the range of anti-cervical cancer concentration. Crude extract of J1 fermentation induced apoptosis and regulated cell cycle in cervical cancer. The active compounds were separated and identified by preparative chromatography, and more than ten compounds were obtained. Our study suggests that the crude extract of J1 fermentation from Endophytic fungi of Ginkgo biloba reduced cell growth, and promoted apoptosis of cervical cancer, and is a potential therapeutic strategy for the treatment of cervical carcinoma.

The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. However, the role of eukaryotic translation initiation factor 3 subunit D (EIF3D) in cervical carcinoma is unknown. This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. There were increases of EIF3D expression mRNA and protein expression levels in patients with cervical carcinoma. Disease-free survival (DFS) and overall surviva (OS) of EIF3D lower expression in patients with cervical carcinoma was higher than those of EIF3D higher expression. EIF3D mRNA expression levels in cervical carcinoma cell lines (AV3, Hela229, CaSki and Hela cells) were up-regulated, compared with cervical normal cell line (UVECs). EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma. EIF3D interacting with GRP78 to reduce the activity of GRP78 in vitro model of cervical carcinoma. The inhibition of GRP78 reduced the effects of EIF3D on Warburg effect in vitro model of cervical carcinoma. Our work identifies EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.IMPACT STATEMENT What is already known on this subject? The incidence of cervical cancer ranks third among all female tumours globally and second in developing countries. What do the results of this study add? This study investigated the effects of EIF3D on cell progression of cervical carcinoma and its underlying mechanism in vivo and vitro models. What are the implications of these findings for clinical practice and/or further research? EIF3D promoted cell growth and Warburg effect in vitro model of cervical carcinoma and the inhibition of EIF3D represents a potential therapeutic strategy for the treatment of cervical carcinoma.

Lipase G, endothelial type (LIPG) is expressed abundantly in tissues with a high metabolic rate and vascularisation. Research on LIPG has focussed on metabolic syndromes. However, the role of LIPG in providing lipid precursors suggests that it might function in the metabolism of carcinoma cells. Analysis in The Cancer Genome Atlas indicated that patients with cervical carcinoma with high LIPG expression had a lower survival prognosis compared with patients with low LIPG expression. The mechanism underlying the effects of LIPG in cervical carcinoma is unclear. The present study aimed to determine the role of LIPG in cervical carcinoma and its mechanism. The results showed that the LIPG expression level was higher in cervical cancer. Downregulation of LIPG expression inhibited cell migration, invasion, proliferation, and the formation of cell colonies, but increased the rate of apoptosis. The Human papillomavirus E6 protein might reduce the expression of miR-148a-3p, relieve the inhibitory effect of miR-148a-3p on LIPG expression, and promote the progression of cervical cancer through the phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin kinase signalling pathway.IMPACT STATEMENT What is already known on this subject? LIPG provides lipid precursors, suggesting that it might function in the metabolism of carcinoma cells What do the results of this study add? LIPG might be regulated by HPV16 E6/miR-148a-3p and promote cervical carcinoma progression via the PI3K/AKT/mTOR signalling pathway. What are the implications of these finding for clinical practice and/or further research? The results indicated that novel treatment and diagnosis strategies for cervical carcinoma could be developed related to LIPG. However, the detailed relationship between LIPG and cervical carcinoma remains to be fully determined.