Interplay of precision therapeutics and MD study: Calocybe indica's potentials against cervical cancer and its interaction with VEGF via octadecanoic acid.

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.

Theoretical evaluation of the impact of diverse treatment conditions by calculation of the tumor control probability (TCP) of simulated cervical cancer Hyperthermia-Radiotherapy (HT-RT) treatments in-silico.

INTRODUCTION: Hyperthermia (HT) induces various cellular biological processes, such as repair impairment and direct HT cell killing. In this context, in-silico biophysical models that translate deviations in the treatment conditions into clinical outcome variations may be used to study the extent of such processes and their influence on combined hyperthermia plus radiotherapy (HT + RT) treatments under varying conditions. METHODS: An extended linear-quadratic model calibrated for SiHa and HeLa cell lines (cervical cancer) was used to theoretically study the impact of varying HT treatment conditions on radiosensitization and direct HT cell killing effect. Simulated patients were generated to compute the Tumor Control Probability (TCP) under different HT conditions (number of HT sessions, temperature and time interval), which were randomly selected within margins based on reported patient data. RESULTS: Under the studied conditions, model-based simulations suggested a treatment improvement with a total CEM43 thermal dose of approximately 10 min. Additionally, for a given thermal dose, TCP increased with the number of HT sessions. Furthermore, in the simulations, we showed that the TCP dependence on the temperature/time interval is more correlated with the mean value than with the minimum/maximum value and that comparing the treatment outcome with the mean temperature can be an excellent strategy for studying the time interval effect. CONCLUSION: The use of thermoradiobiological models allows us to theoretically study the impact of varying thermal conditions on HT + RT treatment outcomes. This approach can be used to optimize HT treatments, design clinical trials, and interpret patient data.

Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021.

BACKGROUND: In Japan, comprehensive cancer statistics data have been collected through national cancer registries, but these data are rarely summarized and reported in research articles. METHODS: Here, we compiled the national registry data on malignant tumors originating from gynecologic organs (ovary, corpus uteri, cervix uteri) in Japan. RESULTS: The number of new patients in 2019 was 13,380, 17,880, and 10,879, respectively, and the number of deaths in 2021 was 5081, 2741, and 2894, respectively. Compared with 40 years ago, the incidence of ovarian cancer has tripled, the incidence of uterine corpus cancer (mainly endometrial cancer) has increased eightfold, the mortality rate of uterine corpus cancer has tripled, and the incidence of cervical intraepithelial cancer has increased ninefold in data standardized by the world population. Compared with the United States, the incidence rate of ovarian cancer has overtaken and the mortality rate of uterine corpus cancer is the same, while both the incidence and mortality rates of cervical cancer are higher in Japan. CONCLUSION: The incidence of gynecologic cancer is increasing significantly in Japan.

Cervical Cancer Therapeutics: An In-depth Significance of Herbal and Chemical Approaches of Nanoparticles.

Cervical cancer emerges as a prominent health issue, demanding attention on a global level for women's well-being, which frequently calls for more specialized and efficient treatment alternatives. Traditional therapies may have limited tumour targeting and adverse side effects. Recent breakthroughs have induced a transformative shift in the strategies employed against cervical cancer. biocompatible herbal nanoparticles and metallic particles made of gold, silver, and iron have become promising friends in the effort to fight against this serious disease and understand the possibility of these nanoparticles for targeted medication administration. this review article delves into the latest advancements in cervical cancer research. The safety and fabrication of these nanomaterials and their remarkable efficacy against cervical tumour spots are addressed. This review study, in short, provides an extensive introduction to the fascinating field of metallic and herbal nanoparticles in cervical cancer treatment. The information that has been examined points to a bright future in which women with cervical cancer may experience fewer side effects, more effective therapy, and an improved quality of life. This review holds promise and has the potential to fundamentally reshape the future of cervical cancer treatment by addressing urgent issues and unmet needs in the field.

Betulinic acid induces apoptosis of HeLa cells via ROS-dependent ER stress and autophagy in vitro and in vivo.

Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention.

Investigation of in-vitro Anti-Cancer and Apoptotic Potential of Garlic-Derived Nanovesicles against Prostate and Cervical Cancer Cell Lines.

OBJECTIVE: Investigate the anti-cancerous potential of garlic-derived nanovesicles (GDNVs), exploring their cytotoxic effects on HeLa and PC-3 cell lines, and elucidate the underlying mechanisms, including apoptosis induction and inhibition of epithelial-mesenchymal transition (EMT). METHODS: GDNVs were isolated using differential centrifugation and ultracentrifugation. Characterization was performed through dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM), and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity assessments on HeLa and PC-3 cell lines using MTT assay. Apoptosis induction was evaluated through nuclear morphology changes and quantification of apoptotic cells using DAPI and PI/annexin V analysis. Western blot of apoptosis-related proteins (bcl-2, bax, caspase-3) was analysed. Anti-metastatic potential was assessed using wound healing assay and EMT transition inhibition. RESULTS: Garlic-derived nanovesicles (GDNVs), characterized by a size of 134.2 nm, demonstrated a substantial and dose- as well as time-dependent anti-proliferative impact on HeLa and PC-3 cell lines. The induction of apoptosis was unequivocally established through discernible modifications in nuclear morphology. The apoptotic cell count in HeLa and PC-3 cells increased by 42.4 ± 4.2% and 38.2 ± 3.2%, respectively. Comprehensive Western blot demonstrated alterations in the expression of key apoptotic regulators, namely bcl-2, bax, and caspase-3, providing robust evidence for the initiation of apoptosis. Furthermore, GDNVs exerted a significant inhibitory effect (p < 0.001) on the migratory potential of both HeLa and PC-3 cells. Moreover, there was a discernible association between GDNVs and the suppression of Epithelial-Mesenchymal Transition (EMT), emphasizing their role in impeding the metastatic potential of these cancer cell lines. CONCLUSION: This study establishes, for the first time, the anti-cancerous potential of GDNVs. The observed dose- and time-dependent anti-proliferative effects, selective cytotoxicity, apoptosis induction, and anti-migratory potential highlight GDNVs as a promising candidate for cancer treatment.

Correlation Between Persistent HPV Infection and Vaginal Microecological Imbalance After Treatment of Cervical High-Grade Squamous Intraepithelial Lesion.

Objective: To analyze the association between persistent human papillomavirus (HPV) infection and vaginal microecological imbalance after surgical treatment of cervical high-grade squamous intraepithelial lesion (HSIL). Methods: This is a retrospective study, 180 cervical HSIL patients admitted to our hospital from May 2019 to May 2021 were selected, of these, 84 were treated with loop electrosurgical excision procedure (LEEP) and 96 with cold knife conization (CKC). Patients were followed up for HPV infection 1 year after surgery. There is a division into a persistent infection group (positive group) and a negative group based on the presence or absence of HPV, the detection technique was PCR amplification. The two groups were compared regarding preoperative HPV infection, vaginal micro-ecological indicators 1 year after surgery, and the correlation between persistent HPV infection and vaginal microecological imbalance. Results: At 1 year after surgery, among 180 cervical HSIL patients, 64 (35.56%) were persistently infected with HPV, with an age of (40.20 ± 4.85) years, including 36 (56.25%) with cervical intraepithelial neoplasia (CIN) grade II, 28 (43.75%) with cervical intraepithelial neoplasia (CIN) grade III, 116 (64.44%) with HPV negative, with an age of (40.22 ± 5.15) years, including 67 (57.76%) with CIN grade II and 49 (42.24%) with CIN grade III, the differences in age and CIN classification between the two groups were not statistically significant (P > .05). Preoperatively, 53 people (82.81%) with HPV viral load >100 RLU/CO in the HPV persistent infection group and 76 people (65.52%) with HPV viral load >100 RLU/CO in the HPV negative group, with statistically significant differences between the two groups (P < .05); The difference in HPV virus typing and HPV infection type between the two groups was not statistically significant (P > .05). At 1 year after surgery, the composition ratio of flora density class IV and flora diversity class IV were significantly higher in the HPV persistent infection group than in the HPV negative group, and the dominant bacteria were mainly gram-positive large bacillus, accounting for 83.33%, the difference between the two groups was statistically significant (P < .05); The differences in Nugent scores and pH values between the two groups were not statistically significant (P > .05). Logistic regression analysis showed that flora density, flora diversity, and dominant bacteria were all independent risk factors for persistent HPV infection after treatment in patients with HSIL (P < .05). Conclusion: After treatment of HSIL patients, clinical attention should be paid to monitoring of HPV infection but also to the changes in vaginal microecology, as timely correction of vaginal microecology can facilitate HPV regression and improve the patient's prognosis.

Radiosensitization by Hyperthermia Critically Depends on the Time Interval.

PURPOSE: Hyperthermia is a potent sensitizer of radiation therapy that improves both tumor control and survival in women with locally advanced cervical cancer (LACC). The optimal sequence and interval between hyperthermia and radiation therapy are still under debate. METHODS AND MATERIALS: We investigated the interval and sequence in vitro in cervical cancer cell lines, patient-derived organoids, and SiHa cervical cancer hind leg xenografts in athymic nude mice and compared the results with retrospective results from 58 women with LACC treated with thermoradiotherapy. RESULTS: All 3 approaches confirmed that shortening the interval between hyperthermia and radiation therapy enhanced hyperthermic radiosensitization by 2 to 8 times more DNA double-strand breaks and apoptosis and 10 to 100 times lower cell survival, delayed tumor growth in mice, and increased the 5-year survival rate of women with LACC from 22% (interval ≥80 minutes) to 54% (interval <80 minutes). In vitro and in vivo results showed that the sequence of hyperthermia and radiation therapy did not affect the outcome. CONCLUSIONS: Shortening the interval between hyperthermia and radiation therapy significantly improves treatment outcomes. The sequence of hyperthermia and radiation therapy (before or after) does not seem to matter.

Radical hysterectomy case volume and cervical cancer treatment in the era of COVID-19: A multi-site analysis of National Cancer Institute-designated Comprehensive Cancer Centers.

OBJECTIVE: To compare radical hysterectomy case volume, cancer stage, and biopsy-to-treatment time of invasive cervical cancer diagnosed before and after onset of the COVID-19 pandemic. METHODS: In a multi-institution retrospective cohort study conducted at 6 large, geographically diverse National Cancer Institute-designated cancer centers, patients treated for newly diagnosed invasive cervical cancer were classified into 2 temporal cohorts based on date of first gynecologic oncology encounter: (1) Pre-Pandemic: 3/1/2018-2/28/2020; (2) Pandemic & Recovery: 4/1/2020-12/31/2021. The primary outcome was total monthly radical hysterectomy case volume. Secondary outcomes were stage at diagnosis and diagnosis-to-treatment time. Statistical analyses used chi-squared and two sample t-tests. RESULTS: Between 3/1/2018-12/31/2021, 561 patients were diagnosed with cervical cancer. The Pre-Pandemic and Pandemic & Recovery cohorts had similar age, race, ethnicity, smoking status, and Body Mass Index (BMI). During Pandemic & Recovery, the mean monthly radical hysterectomy case volume decreased from 7[SD 2.8] to 5[SD 2.0] (p = 0.001), the proportion of patients diagnosed with Stage I disease dropped from 278/561 (49.5%) to 155/381 (40.7%), and diagnosis of stage II-IV disease increased from 281/561 (50.1%) to 224/381 (58.8%). Primary surgical management was less frequent (38.3% Pandemic & Recovery versus 46.7% Pre-Pandemic, p = 0.013) and fewer surgically-treated patients received surgery within 6 weeks of diagnosis (27.4% versus 38.9%; p = 0.025). CONCLUSIONS: Lower radical hysterectomy case volume, a shift to higher cervical cancer stage, and delay in surgical therapy were observed across the United States following the COVID-19 outbreak. Decreased surgical volume may result from lower detection of early-stage disease or other factors.

9-oxo-ODAs suppresses the proliferation of human cervical cancer cells through the inhibition of CDKs and HPV oncoproteins.

Mucosal human papillomavirus (HPV) subtypes 16 and 18 are causative agents of cervical cancer, a leading cause of cancer-related deaths among women worldwide. In Japan, eggplant calyx is a folk remedy used to treat common warts. 9-oxo-(10E,12E)-octadecadienoic acid, isolated from eggplant calyx, may have antitumor effects. This study investigated the antitumor effects of 9-oxo-(10E, 12Z)-octadecadienoic acid and 9-oxo-(10E,12E)-octadecadienoic acid (9-oxo-ODAs) on human cervical cancer cells. 9-oxo-ODAs suppressed the proliferation of human cervical cancer cell lines (HeLa, and SiHa) in a concentration-dependent manner (IC50 = 25-50 µM). FCM analysis revealed that 9-oxo-ODAs induced apoptosis. Transcriptome, proteomics, and enrichment analyses revealed that treatment with 9-oxo-ODAs significantly altered the cell cycle and p53 pathways and decreased cyclin-dependent kinase 1 (CDK1) protein expression. Real-time PCR analysis demonstrated that 9-oxo-ODAs reduced CDK1 mRNA expression in a concentration-dependent manner. In vitro, 9-oxo-ODAs reduced the HPV oncoprotein expression. In ex vivo human cervical cancer tissues, 9-oxo-ODAs decreased CDK1 expression and increased cleaved caspase 3, an apoptosis marker. Further, 9-oxo-ODAs showed the potential to suppressed metastatic formation and growth of cervical cancer in vivo. These findings suggest that 9-oxo-ODAs induce cell cycle arrest and apoptosis in HPV-positive human cervical cancer cells, and this process involves CDK1. Consequently, 9-oxo-ODAs may be potential therapeutic agents for cervical cancer.

A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

Clinical Value Analysis of Serum TK1, SCC-Ag, and MUC-1 in the Diagnosis and Prognosis Evaluation of Cervical Cancer.

Objective: This study aims to analyze the diagnostic and prognostic value of serum thymidine kinase (TK1), squamous cell carcinoma antigen (SCC-Ag), and mucin-1 (MUC-1) in cervical cancer. Methods: This retrospective study included 85 cervical cancer patients as the experimental group treated at our hospital's obstetrics and gynecology department from January 2016 to January 2019. The benign group also consisted of 85 patients with benign lesions treated during the same period, and the comparison group comprised 85 patients with healthy physical examinations at the same time. Results: Serum levels of TK1, SCC-Ag, and MUC-1 were significantly higher in the experimental group than in the benign group and higher in the benign group than in the comparison group (P < .05). Additionally, serum TK1, SCC-Ag, and MUC-1 were higher in the lymph node metastasis group, infiltration depth > 1/2 group, tumor diameter ≥ 4 cm group, and stage III-IV group compared to the non-lymph node metastasis group, infiltration depth ≤ 1/2 group, tumor diameter <4 cm group, and stage I-II group (P < .05). No significant differences in serum TK1, SCC-Ag, and MUC-1 among different pathological types and age groups (P > .05). Moreover, serum TK1, SCC-Ag, and MUC-1 levels were higher in the deceased group compared to the survivor group (P < .05). These markers were negatively correlated with survival time (r value = -0.524, -0.428, -0.516), indicating that as the severity of cervical cancer increased, serum TK1, SCC-Ag, and MUC-1 concentrations also increased. The levels of these markers were significantly higher in deceased patients compared to survivors. Conclusions: Serum levels of TK1, SCC-Ag, and MUC-1 show promise as biomarkers for cervical cancer diagnosis and prognosis. TK1 and SCC-Ag are elevated, while MUC-1 is decreased in cervical cancer patients. Further research is warranted to confirm these findings and explore additional biomarkers.

E7 as a Promising Biomarker for Monitoring the Progression of Cervical Lesions in Patients with HPV 16/18 Infections.

Objective: To investigate the expression of E7 protein and its relationship with the progression and prognosis of cervical pre-cancerous lesions in patients with human papillomavirus (HPV) 16/18 infections. Methods: A total of 211 patients with positive HPV 16/18 were included in this study. Patients were categorized into three groups based on colposcopy results: NILM (Negative for Intraepithelial Lesion or Malignancy), LSIL (Low-Grade Squamous Intraepithelial Lesion), and HSIL (High-Grade Squamous Intraepithelial Lesion). E7 protein levels were quantified using Immunochromatographic Assay and compared using ANOVA. Cervical E7 protein levels were assessed before and one year after cervical cone biopsy in the HSIL group. Results: Among HPV 16/18-positive patients with normal Cervical Thinprep Cytologic Test (TCT) results, E7 protein content exhibited abnormal and significant values (P = .001). Mean E7 protein levels for the NILM, LSIL, and HSIL groups were 44.52 ng/mL, 114.60 ng/mL, and 389.20 ng/mL, respectively, and showed statistical significance (P = .000). In the HSIL group, E7 protein levels in HPV-negative patients were significantly lower one year after cervical cone biopsy compared to before (P = .001). However, HPV-positive patients displayed no significant alteration in E7 protein levels before and after biopsy (P = .08). Conclusions: E7 protein levels in detached cervical cells are closely associated with the severity and prognosis of cervical pre-cancerous lesions, suggesting their potential role as a biomarker for monitoring cervical lesion development.

The Efficacy of Volumetric Modulated Arc Therapy Combined With Chemotherapy, Brachytherapy, and Local Hyperthermia on Patients with Locally Advanced Cervical Cancer: A Retrospective Study.

OBJECTIVE: To evaluate the clinical outcomes of volumetric modulated arc therapy (VMAT) followed by brachytherapy (BT), combined with chemotherapy, and local hyperthermia (HT) on locally advanced cervical cancer (LACC). METHODS: In total, 40 patients with FIGO stage IB1-IVB cervical cancer from January 2016 to December 2018 were selectively enrolled in this study. All patients were treated with VMAT (50.4 Gy/1.8 Gy/28 f) concurrent with cisplatin-based chemotherapy (40 mg/m2, q1w, 6 cycles) and local HT (40.5-41°C for 60 min, BIW). BT (30-36 y/5-6 f, 2 f/w) was conducted after VMAT. Objective response rate (ORR), local control (LC) time, LC rate, progression-free survival (PFS) rate, cancer-specific survival (CSS) rate, overall survival (OS), median time to tumor progression and treatment-related toxicity were evaluated. RESULTS: The median follow-up time was 31 months (8-48). The ORR was 100% at 3 months after treatment and 92.1% at 6 months, respectively. The 1-year, 2-year, and 3-year LC rates were 87.4%, 81.9%, and 70.9%, respectively. The average LC time was 31.50 ± 1.89 months (95% CI 27.79-35.21). The 1-year, 2-year, and 3-year PFS rates were 75.85%, 61.2%, and 51.3%, respectively, while the median PFS was 27.07 months. The 1-year, 2-year, and 3-year OS rates were 95%, 84%, and 79.6%, respectively. In total, 12(30%) patients had grade 3/4 bone marrow suppression. One patient had grade 4 leukopenia. In total, 17 patients had grade 1/2 bone marrow suppression. Two patients had grade 3 nausea and grade 3 vomiting reaction, respectively. No grade 3/4 proctitis and bladder reaction were observed. In the late period of treatment, 1 patient had a rectal hemorrhage. In total, 13 patients had vaginal stenosis. CONCLUSION: VMAT concurrent with chemotherapy, BT, and local HT had a favorable short-term efficacy and acceptable toxicity on cervical cancer, which was an alternative option for LACC.

Cytotoxic Effects of Combinative ZnPcS4 Photosensitizer Photodynamic Therapy (PDT) and Cannabidiol (CBD) on a Cervical Cancer Cell Line.

The most prevalent type of gynecological malignancy globally is cervical cancer (CC). Complicated by tumor resistance and metastasis, it remains the leading cause of cancer deaths in women in South Africa. Early CC is managed by hysterectomy, chemotherapy, radiation, and more recently, immunotherapy. Although these treatments provide clinical benefits, many patients experience adverse effects and secondary CC spread. To minimize this, novel and innovative treatment methods need to be investigated. Photodynamic therapy (PDT) is an advantageous treatment modality that is non-invasive, with limited side effects. The Cannabis sativa L. plant isolate, cannabidiol (CBD), has anti-cancer effects, which inhibit tumor growth and spread. This study investigated the cytotoxic combinative effect of PDT and CBD on CC HeLa cells. The effects were assessed by exposing in vitro HeLa CC-cultured cells to varying doses of ZnPcS4 photosensitizer (PS) PDT and CBD, with a fluency of 10 J/cm2 and 673 nm irradiation. HeLa CC cells, which received the predetermined lowest dose concentrations (ICD50) of 0.125 µM ZnPcS4 PS plus 0.5 µM CBD to yield 50% cytotoxicity post-laser irradiation, reported highly significant and advantageous forms of cell death. Flow cytometry cell death pathway quantitative analysis showed that only 13% of HeLa cells were found to be viable, 7% were in early apoptosis and 64% were in late favorable forms of apoptotic cell death, with a minor 16% of necrosis post-PDT. Findings suggest that this combined treatment approach can possibly induce primary cellular destruction, as well as limit CC metastatic spread, and so warrants further investigation.

Discussion on the necessity of bilateral inguinal lymphatic area irradiation for cervical cancer with invasion of the lower one-third of the vagina.

Context: According to the National Comprehensive Cancer Network guidelines for cervical cancer, patients with cervical cancer invading the lower one-third of the vagina require bilateral inguinal lymphatic area preventive irradiation. However, it is not clear whether they need preventive inguinal area irradiation. Aims: The aim of this study is to evaluate the necessity of bilateral inguinal lymphatic area irradiation for patients with cervical cancer with invasion of the lower one-third of the vagina. Settings and Design: Patients without inguinal lymph node metastasis were divided into preventive radiotherapy and nonpreventive radiotherapy groups. The occurrence of inguinal skin damage, lower extremity edema, and femoral head necrosis was observed during and after treatment. Methods and Material: In total, 184 patients with cervical cancer with invasion of the lower one-third of the vagina were selected. A trial and control method was used to select 180 patients without inguinal lymph node metastasis. Statistical Analysis: Comparison between groups was performed using a t test. Data were enumerated using frequency (percentage), and comparison between groups was performed using a Chi-square test. Results: Imaging examination revealed inguinal lymph node enlargement in 7.07% of patients, and only four cases (2.17%) were further confirmed by pathology. The inguinal lymph node metastasis rate in these patients was very low. The prophylactic irradiation group showed a high occurrence rate of side injury. In the follow-up of both groups, no recurrence was detected in the inguinal lymph nodes. Conclusions: Prophylactic irradiation of inguinal lymph nodes is not essential for patients without pathological metastasis.

The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating E6/E7-HPV Oncogenes and KCNH1 Gene Expression.

Cervical cancer is the fourth most common cancer among women worldwide. The main factor associated with the onset and progression of this neoplasia is the human papillomavirus (HPV) infection. The HPV-oncogenes E6 and E7 are critical drivers of cellular transformation, promoting the expression of oncogenes such as KCNH1. The phytochemical α-mangostin (AM) is a potent antineoplastic and antiviral compound. However, its effects on HPV oncogenes and KCNH1 gene expression remain unknown. This study evaluated the effects of AM on cell proliferation, cell cycle distribution and gene expression, including its effects on tumor growth in xenografted mice. AM inhibited cell proliferation in a concentration-dependent manner, being the most sensitive cell lines those with the highest number of HPV16 copies. In addition, AM promoted G1-cell cycle arrest in CaSki cells, while led to cell death in SiHa and HeLa cells. Of interest was the finding of an AM-dependent decreased gene expression of E6, E7 and KCNH1 both in vitro and in vivo, as well as the modulation of cytokine expression, Ki-67, and tumor growth inhibition. On these bases, we suggest that AM represents a good option as an adjuvant for the treatment and prevention of cervical cancer.

Disparities in Diagnosis and Treatment of Cervical Adenocarcinoma Compared With Squamous Cell Carcinoma: An Analysis of the National Cancer Database, 2004-2017.

OBJECTIVES: The aim of the study are to compare trends in diagnosis and treatment of adenocarcinoma of the cervix (AC) to squamous cell carcinoma of the cervix (SCC) and to examine associations between stage at diagnosis and guideline-concordant treatment with race, age, and insurance type for AC and SCC. MATERIALS AND METHODS: We performed a retrospective cohort study of cervical AC ( n = 18,811) and SCC ( n = 68,421) from the 2004-2017 National Cancer Database. We used generalized linear models to evaluate trends in frequency of histologies and to evaluate associations between race, age, and insurance status with stage of diagnosis and receipt of National Comprehensive Cancer Network guideline-concordant treatment for AC and SCC. RESULTS: The proportion of AC relative to SCC increased from 19.4% (95% CI = 18.4-20.5) to 23.2% (95% CI = 22.2-24.2) from 2004 to 2017 ( p < .001). Compared with SCC, women with AC were younger, more likely to be White, and privately insured ( p < .001). Older women with AC were 44% less likely to be diagnosed with early-stage disease than younger women (adjusted relative risk = 0.56, 95% CI = 0.52-0.60); there was no significant difference for SCC. Black women with AC were 16% less likely to be diagnosed with early-stage disease (adjusted relative risk [aRR] = 0.84, 95% CI = 0.79-0.89) than White women. Women with public insurance were less likely to be diagnosed at an early stage for both AC (aRR = 0.81, 95% CI = 0.78-0.84) and SCC (aRR = 0.79, 95% CI = 0.77-0.81). Rates of guideline-concordant treatment were similar for AC and SCC, with minimal differences by age, race, and insurance. CONCLUSIONS: As the proportion of AC to SCC rises, important race and age-related disparities must be addressed to reduce unnecessary morbidity and death.

PLAU is associated with cell migration and invasion and is regulated by transcription factor YY1 in cervical cancer.

Cervical cancer, one of the most common malignancies, has a poor survival rate. The identification of more biomarkers for cervical cancer diagnosis and therapy is urgently needed. Plasminogen activator urokinase (PLAU) exerts multiple biological effects in various physiological and pathological processes; however the role of PLAU in cervical cancer progression is not fully understood. In the present study, the involvement and transcriptional regulation of PLAU in cervical cancer were explored. The expression of PLAU in cervical cancer was first analyzed, and PLAU was found to be overexpressed. In vitro experiments demonstrated that the migration and invasion of HeLa and HT3 cells were significantly suppressed by PLAU knockdown. Additionally, the core promoter of PLAU was confirmed, and the transcription factor YinYang 1 (YY1) was found to regulate PLAU mRNA expression. Overall, the present study elucidated the direct association between PLAU and cervical cancer, suggesting the YY1/PLAU axis as a potential novel therapeutic target for cervical cancer.

Avascular spaces in radical hysterectomy.

The most common cancer in women worldwide is cervical cancer. For early-stage disease the standard treatment is radical hysterectomy. One of the main issues faced by surgeons performing a radical hysterectomy is the wide variation in the terminology used to define the procedure and the nomenclature used to describe the anatomical spaces critical to the success of the surgery. The aim of this review was to synthesize currently used anatomical landmarks with relation to surgical avascular spaces for the performance of radical hysterectomy.A computer-based comprehensive review of the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and SciSearch databases, as well as National Comprehensive Cancer Network and European Society of Gynaecological Oncology guidelines, was performed. With all relevant data collected, and previous anatomical studies during surgeries and on cadavers performed by authors, a manuscript of the definition of avascular spaces, methods of dissection, and anatomical limits was prepared.Avascular pelvic spaces developed during radical hysterectomy, such as the paravesical, pararectal, ureter tunnel, and paravaginal, were considered and included in the manuscript. A clear definition of avascular spaces may aid a better understanding of the anatomical aspects of the radical hysterectomy. It could improve surgeon knowledge of the structures that need to be preserved and those that need to be resected during a radical hysterectomy. Additionally, the detailed exposure of anatomical boundaries will facilitate the appropriate tailored radicality depending on the risk factors of the disease. Moreover, knowledge of these spaces could make pelvic surgery safer and easier for other types of gynecological and non-gynecological procedures.