Cancer Investigation

Stereotactic Body Radiation Therapy in the Management of Oligometastatic Uterine Cancer

Limited data exist for the use of stereotactic body radiotherapy (SBRT) in oligometastatic uterine cancer. We aimed to evaluate the outcomes of using SBRT for treating oligometastatic uterine cancer. This is a single-institute retrospective study evaluating the use of SBRT in patients with oligometastatic uterine cancer. Survival Endpoints were analyzed using the Kaplan-Meier method. Twenty-three uterine cancer cases with 24 oligometastatic sites were identified, who received SBRT to metastatic sites between 2011 and 2022. The median follow-up period was 30 months (IQR 14-63). The median SBRT dose, fractions, and BED10 were 42 Gy (IQR: 35-45), 5 fx (IQR: 5-5), and 77 Gy (IQR: 60-86). The median time for reirradiation was 30 months (IQR 14-81). Nodal recurrences in 58% of cases were the most common site for SBRT use. The 6-month, 1-, and 2-year local control was 87%, 83%, and 77%, and locoregional control was 83%, 69%, and 64%, respectively. Acute toxicities were observed in 50% of cases with 42% of grade 1 fatigue. Late toxicities were observed in two cases (8%) of grade 2 bowel toxicity. No grade 3 or higher toxicity. SBRT is a safe and effective tool for the management of oligometastatic uterine cancer.

Metabolism-Related Programmed Cell Death: Unveiling Prognostic Biomarkers, Immune Checkpoints, and Therapeutic Strategies in Ovarian Cancer

Ovarian cancer (OC), the gynecologic malignancy with the poorest prognosis, is driven by metabolic reprogramming and dysregulated programmed cell death (PCD). However, their interplay and prognostic significance remain inadequately understood. Transcriptomic data from OC patients and healthy controls (TCGA and GTEx) were analyzed to identify differentially expressed genes (DEGs) intersecting with metabolism-related (MRGs) and PCD-related genes (PCDRGs). Prognostic genes were determined using univariate Cox regression, LASSO, multivariate Cox regression, and stepwise analyses. Consensus clustering revealed enrichment differences, while a risk model and nomogram were developed for outcome prediction. Associations between prognostic genes, immune microenvironment, and drug sensitivity were also assessed. A total of 166 candidate genes were identified, with PLA2G2D, LPCAT3, ARG1, PLA2G4A, and EXOSC3 emerging as significant prognostic markers. The risk model demonstrated marked survival differences, while the nomogram showed robust calibration for survival prediction. Differential immune cell infiltration was observed between risk groups. Additionally, Sinularin and Fulvestrant exhibited variable sensitivity, validated through molecular docking models. Metabolism-related PCD genes were identified as pivotal prognostic markers in OC, providing critical insights for prognostic evaluation and targeted therapy development.

Enhancement of Chemotherapy Efficacy in Cervical Cancer via MAPK Pathway Inhibition by Osimertinib

Addressing recurrent cervical cancer poses a substantial challenge. Osimertinib, an FDA-approved EGFR inhibitor, has emerged as a promising option. Our study examined its potential to enhance paclitaxel's efficacy against cervical cancer. Osimertinib effectively hindered cancer cell growth and induced apoptosis across multiple cell lines. Combined with paclitaxel, it exhibited synergy in suppressing cervical cancer cells. Importantly, osimertinib's inhibitory effect was EGFR-independent; it targeted Mnk phosphorylation, reducing eIF4E activity. In mice, the combined osimertinib-paclitaxel treatment surpassed individual drugs in inhibiting cancer growth. These preclinical findings suggest osimertinib's repurposing as a means to improve paclitaxel's effectiveness in cervical cancer treatment.

New Investigational Drug’s Targeting Various Molecular Pathways for Treatment of Cervical Cancer: Current Status and Future Prospects

Currently, cervical cancer (CC) is the fourth recorded widespread cancer among women globally. There are still many cases of metastatic or recurring disease discovered, despite the incidence and fatality rates declining due to screening identification and innovative treatment approaches. Palliative chemotherapy continues to be the standard of care for patients who are not contenders for curative therapies like surgery and radiotherapy. This article seeks to provide a thorough and current summary of therapies that have been looked into for the management of CC. The authors emphasize the ongoing trials while reviewing the findings of clinical research. Agents that use biological mechanisms to target different molecular pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribosepolymerase (PARP), and epigenetic biological mechanisms epitomize and offer intriguing research prospects.

Women with Atypical Glandular Cells in Japan: The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests

Combination Hormonal Drug Therapy Inhibits In Vitro Growth of Adult Ovarian Granulosa Tumor Cells

This study investigated the mechanism of action and

LDHB Mediates Histone Lactylation to Activate PD-L1 and Promote Ovarian Cancer Immune Escape

To investigate the effects of LDHB on lactylation of programmed cell death 1 ligand (PD-L1) and immune evasion of ovarian cancer. Ovarian cancer cells were transfected with LDHB siRNA and cultured with primed T cells. Cell proliferation and viability were measured by cell counting kit 8 (CCK-8) and colony formation assay. The production of immune factors was detected by enzyme-linked immunosorbent assay (ELISA). The histone lactylation and activity of PD-L1 promoter were measured by chromatin immunoprecipitation (ChIP)-qPCR assay and luciferase reporter gene assay, respectively. Knockdown of LDHB notably inhibited the growth, glucose uptake, lactate production, and ATP production of ovarian cancer cells. Knockdown of LDHB enhanced the killing effects of T cells, led to increased production of immune activation factors IL-2, TNF-α, and IFN-γ, as well as elevated the levels of granzyme B and perforin. Mechanical study identified that LDHB regulated the H3K18 lactylation (H3K18la) modification on PD-L1 promoter region to promote its expression. Overexpression of PD-L1 abolished the immune activation effects that induced by siLDHB. The LDHB modulated lactate production and the histone lactylation on PD-L1 promoter, which ultimately regulated its expression and participated in the immune evasion of ovarian cancer cells.

Does Aspirin Use Reduce the Risk for Ovarian Cancer?

Ovarian cancer is an aggressive malignancy and the leading cause of death among gynecologic cancers. Researchers have evaluated prophylactic medications that potentially avert the manifestation of ovarian cancer, but currently, there are no reliable screening measures for this disease. Nevertheless, the largest study involving aspirin use and ovarian cancer reported a substantive risk reduction from enduring aspirin use. Since there are countervailing data to impugn the potential benefits of aspirin use in staving off ovarian cancer, further research should scrutinize the use of this medication as a prophylactic intervention, especially in women who are at higher risk for developing the disease.

Application in Gene Editing in Ovarian Cancer Therapy

The onset and progression of ovarian cancer (OC) are closely related to dysregulated gene expression. Current treatments for OC are mainly limited to surgery and chemotherapy. However, due to low drug sensitivity, the prognosis OC is exceptionally poor and the recurrence rate remains high. Hence, it is vital to develop new treatment strategies. Gene editing for site-specific genomic modification is a powerful novel tool for the treatment of OC. In this article, current gene editing research for the treatment of OC is reviewed to provide a reference for the clinical application of new approaches to improve treatment outcomes and prognosis.

Quantitative Multiplex Immunofluorescence Evaluation of the Tumor Microenvironment in Pretreatment Tumors of Patients with Metastatic Breast Cancer and Serous Ovarian Carcinoma Treated with Liposomal Eribulin

Eribulin inhibits microtubule polymerization and suppresses epithelial-mesenchymal transition. Conventional pathology approaches have not identified a precise predictive biomarker for Eribulin. We performed qmIF on pre-treatment tissue from 11 patients (6 TNBC, 5 HGSOC) treated with Eribulin-LF. T-lymphocytes were the dominant immune-subset in TME, with higher levels detected in stroma vs tumor (9% vs 2%). Greater density of CD3+ (

Potential Novel Ovarian Cancer Treatment Targeting Myeloid-Derived Suppressor Cells

Diagnosis by biopsy is difficult in the ovary since it is located deep in the abdomen. As a result, ovarian cancer is mostly found insidiously during exploratory laparotomy. Consequently, the early diagnosis of ovarian cancer is often difficult. The likelihood of peritoneal dissemination increases with the progress of ovarian cancer. With further progression, ovarian cancer metastasizes to the momentum, retroperitoneal lymph nodes, large intestine, small intestine, diaphragm, spleen, and other organs. Ovarian cancer has been considered a tumor that has a favorable response to chemotherapy, but more effective treatments are still being explored. Tumors use their own immune escape mechanism to evade host immunity. The immune checkpoint (IC) mechanism, one of the immune escape mechanisms, is established by programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) communication. It has been shown that inhibiting PD-1/PD-L1 communication in various malignancies produces antitumor effects. However, the antitumor effect of ICI monotherapy on ovarian cancer is limited in actual clinical practice. In this review, we describe a novel cancer immunotherapeutic agent that targets myeloid-derived suppressor cells (MDSCs).

Uncertainty and Guilt in Ovarian Cancer Survivorship

Uncertainty is high in the ovarian cancer context; yet, limited research has focused on how uncertainty is experienced and managed by patients/survivors. This study, thus, examined sources and management of uncertainty among ovarian cancer patients/survivors. It analyzed qualitative interview data from 28 patients/survivors and found that possibility of disease recurrence, limited social buffer, and exposure to death contributed to uncertainties in women about finances, health, and relationships. Depending on how uncertainties were appraised, women managed these by adapting, regulating social interaction, or maintaining a sense of control. Also, survivor guilt was identified as a component of ovarian cancer survivorship.

Risk and Prognosis of Second Primary Cancers among Ovarian Cancer Patients, Based on SEER Database

The purposes of the present study were to elucidate the risk and prognostic effect of second primary cancers (SPCs) development, as well as the factors influencing the prognosis of OC patients with SPCs. A statistically significant increase in SPCs risk was observed among OC patients during 2004-2015. The independent factors were used to construct the SPCs-prediction nomogram and the OS-prediction nomogram. Both nomogram were subjected to internal validation and performed well. OC patients with SPCs have a better prognosis than patients without SPCs. Propensity score matching (PSM) was applied to reduce confounding.

Identification of Chemo and Radio-Resistant Sub-Population of Stem Cells in Human Cervical Cancer HeLa Cells

Cervical cancer ranks the second female malignancy after breast cancer. Cancer stem cells (CSCs) are hard to be eradicated, so can recur. We aim to isolate and characterize CSCs from HeLa cells. These cells express clusters of differentiation (CDs), 44 and 24, to be sorted by fluorescence-activated cell sorting (FACS). CD44 CD44

The Clinical Significance and Utility of HPV-DNA Testing in Korean Women with Atypical Glandular Cells in Cervical Pap Tests: An Analysis of 311 Cases at a Single Institution

The aim of this study is to analyze the correlation between clinically significant histologic results and HPV in women with AGC in pap test. Of the 311 women confirmed as AGC, 111 women (35.7%) was identified as positive for HPV. In the AGC analysis, cervical lesions were significantly more common in HPV positive group compared to HPV negative group (61.2 vs. 10.5%,

Perineural Invasion as a Predictive Biomarker of Groin Metastases and Survival Outcomes in Vulvar Cancer: A Meta-Analysis

We searched international databases to identify evidence that refer to the impact of perineural invasion on survival outcomes of patients with squamous cell vulvar cancer. We identified six retrospective cohort studies that investigated 887 patients. Of those, 234 (26.4%) had perineural invasion in the pathology analysis. Women with perineural invasion were more likely to have inguinal lymph node metastases (HR 3.45, 95% CI 1.12, 10.67). The impact of perineural invasion on progression-free survival rates was significant (HR 1.61, 95% CI 1.21, 2.15) as well as its impact on overall survival rates (HR 2.73, 95% CI 1.94, 3.84).

Use of Negative Pressure Wound Therapy Systems after Radical Vulvectomy for Advanced Vulvar Cancer

A retrospective cohort study was performed to evaluate the efficacy of negative pressure wound therapy in improving vulvectomy healing. Women who underwent radical vulvectomy with complete inguinofemoral lymphadenectomy for advanced vulvar cancer were divided into two groups according to immediate postoperative care: patients treated with negative pressure wound therapy using the device applied on the site of the wound (including vulva and inguinal region), and patients receiving conventional care. 18 patients were included in the study. 7 (38.9%) women were treated with negative pressure wound therapy immediately after the surgery and were included in the intervention group, and 11 (61.1%) patients were included in the control group. Women who received negative pressure wound therapy had significantly lower length of stay in the hospital (14.2 ± 4.7 versus 17.1 ± 6.1 days, mean difference -6.90 days, 95% confidence interval -11.91 to -1.89), and significantly lower length for wound healing (-31.90 days, 95% confidence interval -43.48 to -20.32). In conclusion, the utilization of the negative wound pressure therapy may contribute to reduce hospitalization after radical vulvectomy for vulvar cancer. Large and well-designed randomized trials with cost effectiveness analyses are needed to confirm these findings.

Capecitabine-Enhanced Brachytherapy in Locally Advanced Cervical Cancer: A Phase II Non-Randomized Trial on Safety and Efficacy

To evaluate the safety and efficacy of administering capecitabine concurrent with brachytherapy in advanced-stage cervical cancer. Eligible patients with FIGO stage IB2-IVA cervical cancer were enrolled in this phase II non-randomized trial. After external beam chemoradiotherapy (EBRT), patients received capecitabine alongside brachytherapy as radiosensitizer. The primary objective was to assess the tolerability of the combined regimen and its effect on one-year disease-free (DFS) and overall survival rates (OS). Of the 69 patients completed treatment, 18 were enrolled as intervention group and 51 served as controls. Both groups were matched in terms of comorbidities, stage, and response to EBRT. Overall, concurrent capecitabine administration during brachytherapy was safe. At one-year follow-up, one death was recorded in each group, with recurrence rates of 16.7% in the intervention group and 19.6% in the control group. One-year DFS was 82% (95% CI: 54%-98%) in the intervention group and 87% (95% CI: 72%-94%) in the control group, while one-year OS was 93% (95% CI: 53%-98%) and 97% (95% CI: 85%-99%), respectively (for both In conclusion, while capecitabine-augmented brachytherapy was demonstrated to be safe in patients with advanced cervical cancer, its addition did not yield significant improvements in DFS or OS.

Biomarker Potential of DNA Repair Genes XRCC1, XRCC3 and RAD51 Polymorphisms in Ovarian Cancer Patients

Ovarian cancer remains one of the most lethal gynecological malignancies, with a high mortality rate primarily due to late-stage diagnosis. Genetic predispositions play a significant role in its development, alongside environmental and lifestyle factors. The main objective of the study was to check the association of

Search for Healthcare and Breast/Gynecological Cancer Prevention Among Brazilian Lesbian Cisgender Women

PD-1/PD-L1 Inhibitors Monotherapy for the Treatment of Endometrial Cancer: Meta-Analysis and Systematic Review

The efficacy of programmed cell death protein 1(PD-1)/Programmed cell death 1 ligand 1 (PD-L1) inhibitors for endometrial cancer remain controversial, and guidelines are inconsistent on which are preferred therapies for advanced disease, or who develop metastases and recurrence. Therefore, we aimed to estimate the efficacy and safety of PD-1/PD-L1 inhibitors in endometrial cancer on a more complete database by adding multiple randomized trials. A systematic and comprehensive search was carried out in PD-1/PD-L1 inhibitors monotherapy. The ORR of PD-1/PDL-1 inhibitors was 29%, and subgroup analysis showed that the pooled ORR of the proficient mismatch repair (pMMR) group was 4% and which was 45% of the deficient mismatch repair (dMMR) group. The DCR of PD-1/PD-L1 inhibitors was 48%, through subgroup analysis, we found that the DCR of the pMMR group was 21% and which was 58% of the dMMR group. The proportion of patients occurring overall adverse events was 65% and grade three or higher adverse events was 14%. The proficient mismatch repair (pMMR) group and the deficient mismatch repair (dMMR) group showed different results. PD-1/PD-L1 inhibitors had shown little success in the pMMR population and better efficacy in the dMMR population.

Decoding Cervical Cancer Biomarkers: An Integrated Framework of Bioinformatics, Machine Learning, and Experimental Confirmation

Cervical cancer is the fourth most frequent cancer in females, with a high mortality rate globally. Persistent infection with high-risk, oncogenic human papillomavirus (HPV) types is a critical etiologic factor in the progression of the disease. Unfortunately, cervical cancer often remains undiagnosed until advanced stages, hence limiting treatment effectiveness. Therefore, identifying precise and significant biomarkers is crucial. High-throughput sequencing technologies have revolutionized targeted cancer therapy research by generating extensive data for analysis. This study employed bioinformatics and machine learning (ML) approaches to identify dysregulated genes with significant diagnostic value in cervical cancer, utilizing transcriptomics datasets. Seven potential diagnostic biomarker genes (

RNA-Seq Analysis of Clinical Samples from TCGA Reveal Molecular Signatures for Ovarian Cancer

Identifying differentially expressed genes and co-expression modules lead to novel biomarkers. GO, pathway enrichment, network, and tumor stage analysis of 318 ovarian cancer samples from TCGA, categorised into primary and recurrent, pre-menopause and post-menopause, and early and late stage tumors was performed. Upregulated and downregulated genes in primary vs recurrent, early stage vs late-stage and pre-menopause vs post-menopause tumors were 84 and 62, 84 and 35, and 88 and 14, respectively. IRAK2 and CXCL8 had higher expression in recurrent tumors while REG1A had higher expression in post-menopause samples. In late stage tumors constant expression of IRAK2 and REG1A was observed, while that of CXCL8 and EGF decreased. These genes may be potential biomarkers for the diagnosis of the disease.

Diagnostic Accuracy of Intraoperative Frozen Section Analysis in Correlation with Histopathological Diagnosis of Ovarian Tumors in a Tertiary Care Center – A Retrospective Study

Treatment plan for ovarian neoplasms differs for benign, borderline and malignant tumors. With a turnaround time of 15-20 minutes, frozen section has become a reliable intraoperative diagnostic tool. The aim of this study is to correlate the frozen section diagnosis with subsequent histopathologic diagnosis and determine the accuracy of frozen section diagnosis. The study included 152 ovarian tumors, the overall accuracy of frozen section in diagnosing malignancy was 99.34%, whereas that for benign and borderline tumors were 97.37% and 96.71% respectively. However, the accuracy, sensitivity and specificity for borderline tumors and mucinous tumors were found to be low.

TTN Mutation in Endometrial Endometrioid Carcinoma Is Associated with Poor Clinical Outcomes and High Tumor Mutation Burden

Endometrioid endometrial carcinoma (EEC) stands as a prevalent gynecologic malignancy in developed regions. However, predicting relapse cases remains challenging, necessitating the identification of a novel biomarker for EEC relapse. The assessment of tumor mutational burden (TMB) is pivotal for immunotherapy in EEC patients. However, both whole-exome sequencing (WES) and targeted sequencing encountered application-related difficulties. In light of this, standardized and simplified techniques for TMB measurement are imperative. In this study, we employed WES on 25 EEC patients (12 relapsed cases and 13 non-relapsed cases) who accepted hysterectomy surgery (CHCAMS cohort). We additionally obtained a total of 391 tumor samples with clinicopathological features from TCGA website to broaden the study cohort. In the CHCAMS cohort, the

Platinum-Pemetrexed Chemotherapy for Recurrent Ovarian Cancer (ROC): A Single Center Experience

In this retrospective analysis of 36 patients with recurrent ovarian cancer (ROC) treated with platinum pemetrexed doublet ± bevacizumab, the median age was 54.5 years (47-60) and 33 (91.7%) had serous histology. The overall response rate [ORR = complete (CR)+partial (PR) response] was 83.3%. At a median follow-up of 16 months, the median PFS was 13.8 months (95% CI: 10.849-20.580) and median OS 30.6 months, (95% CI: 21.46 months-NR). The incidence of Grade 3/4 anemia, thrombocytopenia, neutropenia and non-hematological toxicity was 19.4%, 3.9%, 16.6%, and 8.3%. Platinum pemetrexed chemotherapy in ROC is safe and effective treatment option.

PARP Inhibitors Rising as an Epoch-Making Strategy in First-Line Maintenance Therapy of Ovarian Cancer: A Systematic Review and Meta-Analysis

To illustrate the accurate location of Poly-ADP-ribose polymerase inhibitor (PARPi) as the first-line maintenance therapy in advanced ovarian cancer (AOC). Search for eligible studies and calculate clinical outcomes. PARPi as a first-line maintenance treatment significantly prolonged the BRCAmut population and the homologous recombination deficiency (HRD) positive population. PARPi as first-line maintenance therapy significantly improves the progression-free survival in AOC, especially in the BRCAmut and HRD positive populations. PARPi has been becoming the standard first-line maintenance therapy for AOC.

Survival Advantage of Lymphadenectomy in Patients with Ovarian Cancer

We investigated the survival effect of lymphadenectomy in ovarian cancer. The five-year progression-free and overall survival in early-stage ovarian cancer were not affected. Preliminary, unadjusted analysis in advanced ovarian cancer suggested an improvement in survival. However, after adjusting for other factors, e.g. ECOG performance status and patients' age, this survival advantage vanished. Our analysis suggests that systemic pelvic and para-aortic lymphadenectomy was not associated with an improvement of the progression-free and overall survival of patients with optimally debulked ovarian cancer.

TTYH3 Promotes Cervical Cancer Progression by Activating the Wnt/ β -Catenin Signaling Pathway

The role of tweety homolog 3 (TTYH3) has been studied in several cancers, including hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. The results showed that TTYH3 is highly expression in cervical cancer tissues and cells and high TTYH3 expression correlates with poor prognosis in patients with cervical cancer. TTYH3 markedly reduced the apoptosis rate and promoted proliferation, migration, and invasion. Silencing of TTYH3 has been shown to have an inhibitory effect on cervical cancer progression. Moreover, TTYH3 enhanced EMT and activated Wnt/β-catenin signaling. Furthermore, TTYH3 knockdown inhibited the tumor growth in vivo. In conclusion, TTYH3 promoted cervical cancer progression by activating the Wnt/β-catenin signaling.

Advance of Circulating Tumor Cells in the Prognosis and Management of Endometrial Cancer

Endometrial cancer (EC) is a common gynecological malignancy and its mortality has been increasing in the last twenty years. A growing body of evidence suggests that circulating tumor cells (CTCs) may provide a more complete tumor profile, facilitate the understanding of the molecular mechanism and individual management of EC patients. In this review, we presented the presence and clinical applications of CTCs and disseminated tumor cells (DTCs) in EC, particularly for EC prognosis and management, also highlighted the diagnostic value of tumor cells in urine of EC patients, aim to help researchers better focus on their study in this field.