Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer.

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.

Vaginal Ovule Loaded with Bismuth Lipophilic Nanoparticles and Cetylpyridinium Chloride Inhibits Human Cervical Carcinoma and Candida albicans Growth.

Bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) are antineoplastic and antimicrobial in vitro. As a next pre-clinical step, a clinically viable dosage form for vaginal application was developed. Compendial pharmacopeial tests (mass uniformity, disintegration, and compressive mechanics) and inductively coupled plasma optical emission spectroscopy were conducted on in-house developed glycerinated gelatin (60:15 v/w) vaginal ovules containing BisBAL NP-CPC. The antimycotic activity of BisBAL NP-CPC vaginal ovules was analyzed using disk diffusion and cell viability XTT assays. The antitumor properties of BisBAL NP-CPC vaginal ovules were assessed by cell viability MTT tests. BisBAL NP-CPC and drug-free vaginal ovules deposited into ex vivo porcine vaginas disaggregated without signs of adverse cytotoxicity within the timespan of clinical efficacy. BisBAL NP-CPC vaginal ovules demonstrated antifungal efficacy comparable to miconazole: C. albicans growth inhibition haloes in diffusion tests were 23 ± 0.968 mm (n = 3) for BisBAL NP-CPC and 20.35 ± 0.899 mm (n = 3) for miconazole. Likewise, BisBAL NP-CPC vaginal ovules reduced HeLa cell growth by 81%, outperforming the clinical reference of 500 µM 5-fluouracil, which induced a 70% growth inhibition. BisBAL NP-CPC incorporated into glycerinated gelatin vaginal ovules constitute an innovative drug delivery system for topical antimycotic and anti-cervical carcinoma treatments.

Computational insights into CRISP3 downregulation in cervical cancer and its cervical lineages pattern.

Background: Cysteine-rich secretory protein 3 (CRISP3) emerges as a potential biomarker in the study of many cancers, including cervical cancer (CC). This study aimed to analyze the expression pattern of CRISP3 in CC patients and CC cell lineages, following treatment with the epigenetic drugs: trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-aza). Methods: The differentially expressed genes identified in GSE63514 were used to construct a protein-protein interaction network. CRISP3 was selected for subsequent analyses. We utilized data from the TCGA and GENT2 projects to evaluate the expression profile and clinical behavior of CRISP3. Additionally, we conducted cell culture experiments to analyze the expression profile of CRISP3 in cells. Results: Low levels of CRISP3 were observed in squamous cell carcinoma (SCC) and human papillomavirus (HPV)16+, along with being associated with worse overall survival (OS). MIR-1229-3p was analyzed, and its high expression was associated with worse prognostic outcomes. In CC-derived cell lines, we observed low levels of CRISP3 in SiHa, followed by SW756, C33A, HeLa, and higher levels in CaSki. All cells were treated with TSA, 5-aza, or both. In all cell lines, treatment with TSA resulted in increased transcription of CRISP3. Conclusion: We identified a significant downregulation of CRISP3 in CC, particularly in cases with HPV16 infection and SCC, which was associated with poorer OS. Preliminary findings suggest that epigenetic treatments with TSA and 5-aza may modulate CRISP3 expression, warranting further research to elucidate its regulatory mechanisms and potential as a prognostic biomarker.

An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma.

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.

Cervical Tuberculosis Mimicking Tumor Persistence: A Case Report.

Tuberculosis can coexist with malignancy in the same organ, but cancer with TB in the cervix is rare. This is a case of cervical tuberculosis diagnosed in a cervical cancer patient after concurrent chemoradiotherapy and brachytherapy. This is the case of a 38-year-old G2P2 (2002) diagnosed with squamous cell carcinoma, large cell non-keratinizing cervix, Stage IIIB. The patient underwent concurrent chemoradiotherapy and brachytherapy. One month after the last brachytherapy dose, the attending physician noted a nodularity on the anterior lip of the cervix. A cervical punch biopsy was done to rule out tumor persistence. The histopathology revealed chronic granulomatous inflammation with Langhan's type multinucleated giant cells consistent with tuberculous infection. She was diagnosed with cervical tuberculosis, postulated to be from latent TB reactivation, and was given Anti-Koch's medication for six months. After receiving Anti-Koch's treatment, the cervical nodularity was no longer appreciated, and the rest of the cervix was smooth on palpation. Her Pap Test was negative for any intraepithelial lesion and was declared with no evidence of carcinoma. A possible latent TB infection should always be screened in cancer patients from high-burden areas or those with close contact treated for tuberculosis because immunosuppression during cancer treatment can cause the reactivation of tuberculous disease. Cervical tuberculosis complicating cervical malignancy is treatable with Anti-Koch's therapy and has not been shown to affect the course of the carcinoma.

Study on the relationship between Methylation of Neuregulin (NRG) Gene and Cervical Carcinoma.

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.

Jackfruit Leaf Protein Hydrolysates Obtained by Enzymatic Hydrolysis of Leaf Protein Concentrate with Pepsin and Pancreatin: Molecular Weight, Cytotoxicity, Antiproliferative Activity, and Oxidative Stress.

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.

A predictive study of genes related to lactic acid metabolism in cervical carcinoma.

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.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.

Case Report: Low-Risk HPV associated Verruco-Papillary squamous cell carcinoma of the cervix.

•Cervical cancer plays a large role in morbidity and mortality for gynecologic cancer.•Most cases are involved with high-risk HPV, rare cases of low-risk HPV associated cancer exists.•Low risk HPV associated cervical cancers have increased difficulty in diagnosis.•No distinction exists in treatment between low and high risk HPV associated cervical cancer.

Double-layer hollow mesoporous silica nanoparticles for ultrasound-guided photodynamic treatment.

Cervical carcinoma persists as a major global public health burden. While conventional therapeutic modalities inevitably cause ablation of adjacent non-tumorous tissues, photodynamic therapy (PDT) offers a targeted cytotoxic strategy through a photosensitizing agent (PS). However, the hydrophobicity and lack of selective accumulation of promising PS compounds such as zinc(II) phthalocyanine (ZnPc) impedes their clinical translation as standalone agents. The present study sought to incorporate ZnPc within double-layer hollow mesoporous silica nanoparticles (DHMSN) as nanocarriers to enhance aqueous dispersibility and tumor specificity. Owing to their compartmentalized design, the hollow mesoporous silica nanoparticles (HMSN) demonstrated enhanced ultrasonic imaging contrast. Combined with the vaporization of the perfluorocarbon perfluoropentane (PFP), the HMSN-encapsulated ZnPc enabled real-time ultrasound monitoring of PDT treatment.In vivo, the innate thermal energy induced vaporization of the DHMSN-carried PFP to significantly amplify ultrasound signals from the tumor site. Results demonstrated biocompatibility, efficient PFP microbubble generation, and robust photocatalytic activity. Collectively, this investigation establishes ultrasound-guided PDT utilizing multi-layer HMSN as a targeted therapeutic strategy for cervical malignancies with mitigated toxicity.

A novel prognostic signature based on cancer stemness and metabolism-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma.

BACKGROUND: CESC is the second most commonly diagnosed gynecological malignancy. Given the pivotal involvement of metabolism-related genes (MRGs) in the etiology of multiple tumors, our investigation aims to devise a prognostic risk signature rooted in cancer stemness and metabolism. METHODS: The stemness index based on mRNA expression (mRNAsi) of samples from the TCGA dataset was computed using the One-class logistic regression (OCLR) algorithm. Furthermore, potential metabolism-related genes related to mRNAsi were identified through weighted gene co-expression network analysis (WGCNA). We construct a stemness-related metabolic gene signature through shrinkage estimation and univariate analysis, thereby calculating the corresponding risk scores. Moreover, we selected corresponding DEGs between groups with high- and low-risk score and conducted routine bioinformatic analyses. Furthermore, we validated the expression of four hub genes at the protein level through immunohistochemistry (IHC) in samples obtained from our patient cohort. RESULTS: According to the findings, it was found that six genes-AKR1B10, GNA15, ALDH1B1, PLOD2, LPCAT1, and GPX8- were differentially expressed in both TCGA-CSEC and GEO datasets among 23 differentially expressed metabolism-related genes (DEMRGs). mRNAsi exhibited a notable association with the extent of key oncogene mutation. The results showed that the AUC values for forecasting survival at 1, 3, and 5 years are 0.715, 0.689, and 0.748, individually. We observed a notable association between the risk score and different immune cell populations, along with enrichment in crucial signaling pathways in CESC. Four genes differentially expressed between different risk score groups were validated by IHC to be highly expressed in the CESC samples at the protein level. CONCLUSION: The current investigation indicated that a 3-gene signature based on stemness-related metabolic and 4 hub genes with differential expression between high and low-risk score subgroups may serve as valuable prognostic markers and potential therapeutic targets in CESC.

DBD-FISH Using Specific Chromosomal Region Probes for the Study of Cervical Carcinoma Progression.

Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.

circ_0039787 promotes cervical cancer cell tumorigenesis by regulation of the miR-877-5p-KRAS axis.

Circular RNA (circRNA) is a novel type of RNA that plays an important role in the occurrence and development of many malignant tumors. However, the potential regulatory role and molecular mechanisms of circRNAs in cervical cancer (CC) are still not clear. Here, we explored circRNAs associated with CC from the Gene Expression Omnibus (GEO) datasets GSE113696 and GSE102686. We initially identified circ_0039787, which is derived from exons 2 to 3 of the C16orf70 gene. We observed that circ_0039787 is mainly located in the cytoplasm and is more stable than its linear counterpart, C16orf70. circ_0039787 is significantly upregulated in CC tissues and cells. In addition, functional gain and loss experiments demonstrated that circ_0039787 promotes the proliferation, migration, and invasion of CC cells in vitro and the growth of CC tumors in vivo. Mechanistically, circ_0039787 promotes CC tumor progression by competitively absorbing miR-877-5p to alleviate the inhibitory effect of miR-877-5p on Kirsten Rat Sarcoma viral oncogene homolog (KRAS) expression. Overall, our results suggest that circ_0039787 could serve as a promising diagnostic biomarker and potential therapeutic target for CC patients.

Human serum albumin-bound paclitaxel nanoparticle inhibits cervical carcinoma cell proliferation and oxidative damage through CYP3A4 and CYP2C8.

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 < 0.05). Under Nano-HSA-PTX intervention, the proliferation, invasion, migration and oxidative damage of HeLa and SiHa were significantly decreased compared with the control and PTX groups, while the apoptosis was increased (P < 0.05). Besides, elevated CYP3A4 and CYP2C8 levels were observed in CC cells, which were inhibited by Nano-HSA-PTX and PTX (P < 0.05). Finally, tumorigenesis experiments in nude mice revealed that Nano-HSA-PTX could inhibit tumor growth. Conclusion: Compared with PTX, Nano-HSA-PTX has a superior effect of inhibiting CC activity. And this mechanism of action was carried out by inhibiting the expression of CYP3A4 and CYP2C8.

Metachronous Squamous Cell Carcinomas of the Uterine Cervix and Lung: True Metachrony or Metastasis.

Human papillomaviruses (HPV) are a big group of infection agents with oncogenic potential, especially regarding squamous epithelium. Some high-risk variants are key in the development of squamous cell carcinomas (SCC) across multiple systems, the most affected of which is the female reproductive system, but also parts of the gastrointestinal tract, head, and neck SCC, and cutaneous and pulmonary (bronchogenic) SCCs. In cases where a patient develops two SCCs in different systems, often the main question is whether these tumors are synchronous, metachronous, or if one of the tumors is a metastasis from the other, with HPV testing and stereotype identification often being of aid in differentiating between these. Herein, we report the case of a female patient in her 50s, initially diagnosed with SCC of the uterine cervix. The patient remained stable for three calendar years after completing preoperative radiotherapy, surgical resection, and postoperative chemo-radiotherapy. At that point, she developed respiratory symptoms, and radiography suggested a pulmonary malignancy. After undergoing surgical resection of the pulmonary lesion, histological specimens were initially interpreted to be a metachronous pulmonary SCC. Immunohistochemical testing proved that both the cervical and pulmonary lesions were HPV-associated, with further testing proving that both lesions were associated with high-risk HPV (genotype 16). Based on the clinical history and aggregated data, the pulmonary lesion was interpreted as a metastatic and not a metachronous one, and the patient is currently undergoing treatment for metastatic disease.

RACK1 promotes the occurrence and progression of cervical carcinoma.

BACKGROUND: RACK1 has been identified as a multifunctional cytosolic protein, and plays a pivotal role in multiple biological responses involved in several kinds of tumors, while its effect in cervical cancer has not been well elucidated yet. The study aimed to investigate the role of RACK1 in cervical cancer occurrence and progression. METHODS: The expression of RACK1 in cervical specimens was measured by immunohistochemical staining and Western blot assay. Transgenic mice were used to detect the role of RACK1 in modulating tumorigenesis in vivo. Cervical carcinoma cell lines were used to explore the underlying mechanisms of RACK1 on the behaviors of tumor cells in vitro. RESULTS: We found that RACK1 expression was upregulated in cancer tissues compared with adjacent tissues, and its expression was gradually increased from cervictis, and cervical intraepithelial neoplasis (CIN) to carcinoma. Genetic overexpression of RACK1 facilitated tumor formation and growth in nude mice. Mechanism studies disclosed that RACK1 over-expression prolonged the G0 /G1 phase by up-regulating the expression of cyclinD1, down-regulating p21 and p27 probably by modulating the phosphorylation of AKT. CONCLUSIONS: Taken together, we concluded that RACK1 stimulates tumorigenesis and progression of cervical cancer via modulating the proliferation of tumor cells, implying that targeting RACK1 may serve as a promising method for cervical cancer therapy.

Small Cell Cervical Carcinoma in Pregnancy: Therapeutic Options for an Aggressive Cancer Diagnosis.

Neuroendocrine small cell cervical carcinoma is an aggressive cancer which accounts for approximately 1 to 3% of all cervical neoplasms. Therapy must be altered in pregnancy to optimize maternal-fetal outcomes. A 39-year-old woman presented for a routine prenatal visit and was noted to have a grossly abnormal cervix. Cervical biopsies confirmed small cell carcinoma. At 19 weeks' gestation, chemotherapy was initiated. The patient delivered at 34 weeks' gestation to initiate radiation therapy. Six months later, she was diagnosed with metastatic disease and died from cancer complications. In pregnancy, treatment modalities for small cell cervical carcinoma are based on the patient's gestational age at diagnosis. While aggressive early treatment is preferred, platinum-based chemotherapy can be initiated in the second trimester and radiation therapy delayed until delivery. Small cell cervical carcinoma complicating pregnancy requires aggressive treatment. Chemotherapy in the second trimester with planned delayed radiation therapy, may optimize fetal outcomes.

Constructed competitive endogenous RNA network and patterns of immune infiltration revealing the prognostic signature for cervical cancer.

Aim: To investigate the relationship between potential abnormal epigenetic modification and immune cell infiltration in patients with cervical carcinoma. Materials & methods: RNA expression profiles from The Cancer Genome Atlas database were used to explore the relationship between key biomarkers and tumor-infiltrating immune cells and for clinical specimen validation. Results: Two nomogram models were developed, one with specific ceRNA and the other based on biological markers of related tumor-infiltrating immune cells. Moreover, a key biomarker (RIPOR2), which was significantly relevant to CD8 T cells. Conclusion: RIPOR2 and CD8 T cells play a crucial role in the development and progression of cervical carcinoma, suggesting their potential as markers for guiding future therapeutic strategies.

Immunohistopathological Study of Papillary Squamotransitional Carcinoma of Uterine Cervix.

INTRODUCTION: Papillary squamotransitional cell carcinoma (PSTCC) arising from the uterine cervix is a distinctive histomorphological subtype of squamous cell carcinoma (SCC) not otherwise specified (NOS) of cervical epithelial tumors. AIM: The present study was undertaken to study the histopathological features and immunoexpression of CK7, CK20, p53 and Ki-67 in PSTCC of the cervix. MATERIALS AND METHODS: This study included 43 cases of PSTCC of cervix. A technique of manual tissue array was employed along with IHC staining of entire section in some cases. The expression pattern of CK7, CK 20, p53 and Ki67 in PSTCC was studied and clinico-pathological correlation of various parameters with IHC expression of CK7 and CK20 was observed. Results were subjected to statistical analysis and were considered significant when the p-value was less than 0.05. RESULTS: Out of 43 PSTCC cases, there were 38 squamotransitional type and 5 papillary type. Histomorphologically, all the cases studied were having fused papillae with rounded contours and fibrovascular cores with highest number of cases having intermediate cell type morphology (86%). Stromal invasion was seen in 74.4% of cases. Koilocytosis were seen in 39.3% of cases. Thirty-two cases showed CK7 immunopositivity (+) and CK20 immunonegativity (-), nine cases were both CK7 and CK20 - and two cases were CK7- and CK20+. Among them 90.7% cases were p53 positive and all cases were positive for Ki67 immunostaining with highest number of cases showing moderate proliferative activity (74.4%); followed by nine cases showing high (20.93%) and two cases showing low proliferative activity (4.65%). CONCLUSION: The distinct histomorphology and CK7/CK20 immnunoprofile of PSTCC along with Ki67 and p53 could help in arriving at an accurate diagnosis as well predicting its biological behavior.