Impact of HPV strains on molecular mechanisms of cervix cancer.

PURPOSE: Cervical cancer accounts for a high number of deaths worldwide. Risk factors are extensive for cervix cancer but Human papillomavirus (HPV) plays a prime role in its development. Different strains of HPV are prevalent globally, which show different grades of mortality and morbidity among women. This study is planned to evaluate the molecular mechanism of different strains of HPV infection and progression leading to cervix cancer. METHODS: This review includes different research articles on cervix cancer progression reported from India and all over the world. RESULTS: HPV 16 and 18 are prevalent strains using heparan sulfate-independent and dependent pathways for viral replication inside the cell. It also uses transcription mechanisms through NF-kappa B, FOXA-1, and AP-1 genes while strains like HPV-35, 45, and 52 are also predominant in India, which showed a very slow mechanism of progression due to which mortality rate is low after their infection with these strains. CONCLUSION: HPV uses E6 and E7 proteins which activate NF-kappa B and AP-1 pathway which suppresses the tumor suppressor gene and activates cytokine production, causing inflammation and leading to a decrease in apoptosis due to Caspase-3 activation. In contrast, the E7 protein involves HOXA genes and decreases apoptotic factors due to which mortality and incidence rates are low in viruses that use E7 motifs. Some HPV strains employ the cap-dependent pathway, which is also associated with lower mortality and infection rates.

Cisplatin-induced bone marrow failure in an adult patient with Fanconi anemia.

INTRODUCTION: Fanconi anemia (FA) is a genetic disorder characterized by bone marrow failure typically developing in the first decade of life, congenital abnormalities, and an increased predisposition to malignancy. However, patients with FA can remain undiagnosed until adulthood and present with solid organ malignancies. Due to impaired DNA repair mechanisms, patients with FA are highly susceptible to severe bone marrow toxicity when treated with cisplatin. CASE REPORT: A 38-year-old woman, diagnosed with locally advanced squamous cell carcinoma (SCC) of the uterine cervix, underwent treatment with weekly cisplatin concurrent with radiotherapy. After the second week of cisplatin treatment, she presented with severe pancytopenia. The prolonged and severe pancytopenia following cisplatin and radiation, along with cervical SCC in the absence of risk factors and the presence of parental consanguinity, raised the possibility of FA as the underlying cause. Whole exome sequencing revealed a homozygous FANCI c.668A > C (p.Lys223Thr) missense variant confirming the diagnosis of FA. MANAGEMENT AND OUTCOME: The pancytopenia exhibited a protracted course, necessitating admission and supportive treatment with antibiotics, red blood cell and platelet transfusions, as well as filgrastim and eltrombopag. Eventually, the pancytopenia improved after approximately 40 days of hospitalization. DISCUSSION: SCC of the head and neck or gynecologic organs in a young adult without known risk factors should prompt consideration of FA. Cisplatin should be avoided in patients with FA.

The Clinical Course of the Late Toxicity of Definitive Radiotherapy in Cervical Cancer.

Background and Objectives: This study aimed to investigate the clinical course and characteristics of late toxicity over time following the completion of definitive radiotherapy (RT) in patients with cervical cancer. Materials and Methods: We retrospectively reviewed the medical records of 60 patients with cervical cancer who underwent pelvic external beam radiotherapy followed by intracavitary brachytherapy. Late toxicity was assessed for the lower gastrointestinal (GI) tract and bladder organ at 6, 12, 24, 36, and >36 months post-RT. We examined the onset and prevalence of late toxicity at each time point. Clinical remission and interventions for managing late toxicity were also investigated. Results: The peak onset of lower GI toxicity occurred 12 months after RT completion, with a median symptom duration of 9.9 months (range, 0.1-26.3 months), and exhibited its highest prevalence rate of 15.5% at 24 months post-RT. Most GI toxicities developed and resolved within three years post-RT, with a prevalence rate of 8.1% at three years, followed by a decreasing trend. Bladder toxicity first peaked at 24 months post-RT and continued to occur beyond 36 months, showing the re-increasing pattern in the prevalence rate after 36 months (23.5%). In terms of clinical remission, 66.7% of lower GI toxicities (12 of 18 patients) and 60% of bladder toxicities (9 of 15 patients) achieved complete remission by the last follow-up date. Conclusions: Late toxicities of the GI and bladder following definitive RT in cervical cancer are partially reversible and exhibit distinct patterns of onset and prevalence over time. A systematic follow-up strategy should be established for the early detection and timely intervention of late toxicity by understanding these clinical courses.

Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self-collected samples.

In cervical cancer screening programs, the detection of high-risk human papillomavirus (HR-HPV) is now widely implemented on physician-collected samples and has expanded to include self-collected samples. The use of a cellularity control (CC) is needed to reduce false-negative HPV results. An external mRNA CC for the HPV APTIMA® assay was assessed for its analytical performance and the results were compared with both cervix cytobrush samples taken by physicians and self-collected vaginal samples from 148 women. The performance of the CC was adjusted to control for the presence of cellular mRNA in the ThinPrep® and Multitest® transport media. This CC is user-friendly but implies to perform two independent assays on PANTHER® automate. Self-collected vaginal sampling gives a lower median CC results (13.2 vs. 16.9 min) but a higher risk of negative CC results (3.3 vs. 0%). The usefulness of the CC for the HR-HPV assay may be optimized by the definition of a threshold for a minimum cell number to be tested to increase confidence in HPV-negative results. The systematic use of an RNA CC increases confidence for HPV RNA assays on self-collected vaginal samples.

High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial.

OBJECTIVE: Radiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer. METHODS: This was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival. RESULTS: Progression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%). CONCLUSION: High-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS. CLINICAL TRIAL INFORMATION: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.

Prognostic significance of FIGO 2018 staging of loco-regionally advanced cervical cancer (LRACC) with the use of MRI and PET and implications for treatment selection.

INTRODUCTION: The FIGO 2018 staging of cervix cancer recognizes a total of 11 categories of loco-regionally advanced cervix cancer (LRACC). Whilst incorporating imaging is an improvement over clinical staging (FIGO 2009), this had led to more categories of disease which are not prognostically discrete groups. We aimed to analyze survival according to 2018 FIGO stages of cervix cancer and identify isoprognostic groups of patients based on primary tumor volume and nodal status. METHODS: Patients referred for radiotherapy with curative intent between 1996 and 2014 were eligible. Baseline clinico-pathological and follow up information was retrieved from an ethics-approved institutional prospective database. Patients were classified according to FIGO 2018 staging based on histo-pathology, MRI (tumor volume and local compartmental spread assessment) and PET results (nodal spread). Kaplan-Meier method was used to estimate survival at five years. Following survival analysis using recognized prognostic factors, isoprognostic categories were identified and merged to form 5 isoprognostic groups. RESULTS: Seven hundred and forty-four LRACC patients were included. The median (IQR) follow-up was 5.1 (2.6-8.4) yrs. Stage migration occurred in most patients, showing heterogeneous 5 years survival according to 2018 FIGO stages. In contrast progressively worsening prognosis could be demonstrated in the 5 observed isoprognostic clusters (p < 0.002). CONCLUSION/IMPLICATIONS: Prognosis in LRACC depends on the interplay between primary tumor characteristics, type of local spread and nodal disease. A prospective study of survival and patterns of failure according to isoprognostic clusters would be useful to determine the most appropriate treatment modality and estimate survival as well as better patient selection for clinical trials.

Deep Learning-based Non-rigid Image Registration for High-dose Rate Brachytherapy in Inter-fraction Cervical Cancer.

In this study, an inter-fraction organ deformation simulation framework for the locally advanced cervical cancer (LACC), which considers the anatomical flexibility, rigidity, and motion within an image deformation, was proposed. Data included 57 CT scans (7202 2D slices) of patients with LACC randomly divided into the train (n = 42) and test (n = 15) datasets. In addition to CT images and the corresponding RT structure (bladder, cervix, and rectum), the bone was segmented, and the coaches were eliminated. The correlated stochastic field was simulated using the same size as the target image (used for deformation) to produce the general random deformation. The deformation field was optimized to have a maximum amplitude in the rectum region, a moderate amplitude in the bladder region, and an amplitude as minimum as possible within bony structures. The DIRNet is a convolutional neural network that consists of convolutional regressors, spatial transformation, as well as resampling blocks. It was implemented by different parameters. Mean Dice indices of 0.89 ± 0.02, 0.96 ± 0.01, and 0.93 ± 0.02 were obtained for the cervix, bladder, and rectum (defined as at-risk organs), respectively. Furthermore, a mean average symmetric surface distance of 1.61 ± 0.46 mm for the cervix, 1.17 ± 0.15 mm for the bladder, and 1.06 ± 0.42 mm for the rectum were achieved. In addition, a mean Jaccard of 0.86 ± 0.04 for the cervix, 0.93 ± 0.01 for the bladder, and 0.88 ± 0.04 for the rectum were observed on the test dataset (15 subjects). Deep learning-based non-rigid image registration is, therefore, proposed for the high-dose-rate brachytherapy in inter-fraction cervical cancer since it outperformed conventional algorithms.

Recent Advances and Adaptive Strategies in Image Guidance for Cervical Cancer Radiotherapy.

The standard of care for locally advanced cervical cancer is external beam radiotherapy (EBRT) with simultaneous chemotherapy followed by an internal radiation boost. New imaging methods such as positron-emission tomography and magnetic resonance imaging have been implemented into daily practice for better tumor delineation in radiotherapy planning. The method of delivering radiation has changed with technical advances in qualitative imaging and treatment delivery. Image-guided radiotherapy (IGRT) plays an important role in minimizing treatment toxicity of pelvic radiation and provides a superior conformality for sparing the organs at risk (OARs) such as bone marrow, bowel, rectum, and bladder. Similarly, three-dimensional image-guided adaptive brachytherapy (3D-IGABT) with computed tomography (CT) or magnetic resonance imaging (MRI) has been reported to improve target coverage and reduce the dose to normal tissues. Brachytherapy is a complementary part of radiotherapy treatment for cervical cancer and, over the past 20 years, 3D-image-based brachytherapy has rapidly evolved and established itself as the gold standard. With new techniques and adaptive treatment in cervical cancer, the concept of personalized medicine is introduced with an enhanced comprehension of the therapeutic index not only in terms of volume (three-dimensional) but during treatment too (four-dimensional). Current data show promising results with integrated IGRT and IGABT in clinical practice and, therefore, better local control and overall survival while reducing treatment-related morbidity. This review gives an overview of the substantial impact that occurred in the progress of image-guided adaptive external beam radiotherapy and brachytherapy.

High expression level of CXCL1/GROα is linked to advanced stage and worse survival in uterine cervical cancer and facilitates tumor cell malignant processes.

BACKGROUND: CXCL1 belongs to a member of the ELR + CXC chemokine subgroups that also known as GRO-alpha. It has been recognized that several types of human cancers constitutively express CXCL1, which may serve as a crucial mediator involved in cancer development and metastasis via an autocrine and/or paracrine fashion. However, the expression pattern and clinical significance of CXCL1 in human uterine cervix cancer (UCC), as well as its roles and mechanisms in UCC tumor biology remains entirely unclear. METHODS: The expression and clinical significance of CXCL1 in UCC tissues was explored using immunohistochemistry and bioinformatics analyses. The expression and effects of CXCL1 in HeLa UCC cells were assessed using ELISA, CCK-8 and transwell assays. Western blotting experiments were performed to evaluate the potential mechanism of CXCL1 on malignant behaviors of HeLa UCC cells. RESULTS: The current study demonstrated that CXCL1 was expressed in HeLa UCC cells, PHM1-41 human immortalized cervical stromal cells, as well as cervical tissues, with UCC tissues having an evidently high level of CXCL1. This high level of CXCL1 in cancer tissues was notably related to poor clinical stages and worse survival probability, rather than tumor infiltration and patient age. In addition, CXCL1 expression was extremely correlated with CCL20, CXCL8 and CXCL3 cancer-associated chemokines expression. In vitro, the growth and migration abilities of HeLa cells were significantly enhanced in the presence of exogenous CXCL1. Gain-function assay revealed that CXCL1 overexpression significantly promoted growth and migration response in HeLa cells in both autocrine and paracrine manners. Finally, we found that CXCL1 overexpression in HeLa cells influenced the expression of ERK signal-related genes, and HeLa cell malignant behaviors derived from CXCL1 overexpression were further interrupted in the presence of the ERK1/2 blocker. CONCLUSION: Our findings demonstrate the potential roles of CXCL1 as a promoter and a novel understanding of the functional relationship between CXCL1 and the ERK signaling pathway in UCC.

Assessment of Sexual Dysfunction in Cervical Cancer Patients after Different Treatment Modality: A Systematic Review.

Background and Objectives: Cervical cancer is a leading cause of mortality among women. Chemo-radiation followed by interventional radiotherapy (IRT) is the standard of care for stage IB-IVA FIGO. Several studies have shown that image-guided adaptive IRT resulted in excellent local and pelvic control, but it is associated with vaginal toxicity and intercourse problems. The purpose of this review is to evaluate the dysfunctions of the sexual sphere in patients with cervical cancer undergoing different cervix cancer treatments. Materials and Methods: We performed a comprehensive literature search using Pub med, Scopus and Cochrane to identify all the full articles evaluating the dysfunctions of the sexual sphere. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Results: One thousand three hundred fifty-six women included in five studies published from 2016 to 2022 were analyzed. The median age was 50 years (range 46-56 years). The median follow-up was 12 months (range 0-60). Cervical cancer diagnosis and treatment (radiotherapy, chemotherapy and surgery) negatively affected sexual intercourse. Sexual symptoms such as fibrosis, strictures, decreased elasticity and depth and mucosal atrophy promote sexual dysfunction by causing frigidity, lack of lubrication, arousal, orgasm and libido and dyspareunia. Conclusions: Physical, physiological and social factors all contribute to the modification of the sexual sphere. Cervical cancer survivors who were irradiated have lower sexual and vaginal function than the normal population. Although there are cures for reducing discomfort, effective communication about sexual dysfunctions following treatment is essential.

Gynaecological cancers and their cell lines.

Cell lines are widely used for various research purposes including cancer and drug research. Recently, there have been studies that pointed to discrepancies in the literature and usage of cell lines. That is why we have prepared a comprehensive overview of the most common gynaecological cancer cell lines, their literature, a list of currently available cell lines, and new findings compared with the original studies. A literature review was conducted via MEDLINE, PubMed and ScienceDirect for reviews in the last 5 years to identify research and other studies related to gynaecological cancer cell lines. We present an overview of the current literature with reference to the original studies and pointed to certain inconsistencies in the literature. The adherence to culturing rulesets and the international guidelines helps in minimizing replication failure between institutions. Evidence from the latest research suggests that despite certain drawbacks, variations of cancer cell lines can also be useful in regard to a more diverse genomic landscape.

Feasibility of implementing a cervix cancer-specific patient-reported outcome measure in routine ambulatory clinics.

OBJECTIVE: To evaluate the implementation of a cervix cancer-specific patient-reported outcome measure, the European Organization for Research and Treatment of Cancer Quality of Life Cervical Cancer module (EORTC QLQ-CX24), into gynecologic oncology clinics. METHODS: This was a prospective, multi-institutional, cross-sectional study involving cervix cancer patients previously treated with curative intent radiotherapy who were attending routine follow-up appointments. Between January 2017 and August 2018, eligible patients were approached to complete the EORTC QLQ-CX24 prior to their clinical encounter and then review it with their oncologist. Patient and oncologist experience was evaluated using Feedback Questionnaires following the encounter. Descriptive statistics were used to summarize the results of the EORTC QLQ-CX24 and Feedback Questionnaires. Open-ended questions within the Feedback Questionnaires were analyzed to identify themes. RESULTS: Eighty-four patients consented to participate in the study. Of these, 80 (95.2%) completed the EORTC QLQ-CX24 and 76 (90.4%) completed both the EORTC QLQ-CX24 and the Feedback Questionnaires. There were high rates of completion for most items within the EORTC QLQ-CX24 (93-98%), except for items pertaining to vaginal symptoms and sexual health (34-35%). All eligible oncologists participated (n = 9). Overall, patients and oncologists positively endorsed use of the questionnaire during clinical encounters. The majority of patients (80%) and oncologists (89%) reported use of the questionnaire improved communication, including discussion of sensitive topics. Interestingly, only a minority of patients and oncologists stated a perceived preference for electronic completion (18% and 44%, respectively). CONCLUSION: Implementation of the EORTC QLQ-CX24 in gynecologic oncology clinics was feasible and acceptable according to patients and oncologists.

Chemoradiotherapy with hyperthermia versus chemoradiotherapy alone in locally advanced cervical cancer: a systematic review and meta-analysis.

PURPOSE: Concurrent chemoradiotherapy (CCRT) is recommended as the standard treatment for locally advanced cervical cancer (LACC). However, the synergistic effect of hyperthermia (HT) with CCRT remains unclear. Therefore, we performed a meta-analysis to evaluate the effect of HT with CCRT on LACC patients. METHODS AND MATERIALS: A systematic literature search was conducted on the MEDLINE, PubMed, Embase, Cochrane library and SCOPUS databases for articles that compared CCRT with HT and CCRT alone as treatments for LACC. Hazard ratios (HRs) and risk ratios (RRs) were used to compare five-year overall survival (OS), local relapse-free survival (LRFS) and incidence of acute and chronic toxicity between the two treatments. RESULTS: Two articles out of 2860 were finally selected for analysis. A total of 536 patients were evaluated (CCRT with HT group: 268, CCRT group: 268). FIGO stages I-II and III-IV were found in 295 (55.0%) and 241 patients (45.0%), respectively. The CCRT with HT group had significantly better five-year OS than the CCRT group (HR 0.67, 95% confidence interval [CI] 0.47-0.96, p = 0.03). LRFS of patients was superior in the CCRT with HT group than in the CCRT group, but without significance (HR 0.74, 95% CI 0.49-1.12; p = 0.16). Moreover, there was no difference between the two groups regarding acute and chronic toxicity. CONCLUSION: This systematic review and meta-analysis showed that CCRT with HT significantly improved OS in LACC patients without increasing acute and chronic toxicity. Therefore, tri-modality treatment could be a feasible approach for patients with LACC.

Diagnostic performance of immediate colposcopy among women with high-risk human papillomavirus (HPV) other than HPV 16/18 and normal cytology.

AIM: Persistent infection with 1 of 14 high-risk genotypes human papillomavirus (HPV) genotypes is the crucial for the development of high-grade cervical cancer precursors. The reassuring management of women with cytology negative, high-risk HPV (HrHPV) positive is important especially after the widespread use of HPV testing either as a cotest. The aim of our study was to compare the colposcopic biopsy results of women with HPV 16/18 with other Hr-HPV genotypes and determine positive predictive values (PPV) for CIN2+ of other HR HPV genotypes. METHODS: We prospectively had included the women with negative cytology and positive Hr-HPV test other than HPV 16/18. Control group was composed of women with negative cytology positive test results for either HPV 16 or HPV 18. Women with HrHPV positive, cytology negative referred to immediate colposcopy. RESULTS: The prevalence of CIN1 and CIN2 is significantly higher in HPV 16/18 group than pooled other HrHPV group (34.1% vs 17.5%, P = 0.01 for CIN 1+; 14.8% vs 5.2%, P = 0.03 for CIN 2+). The prevalence of CIN3 was almost three fold in women with HPV 16/18 (9.1% vs 3.1%). PPV for CIN 2+ was 16.4 (9.1-27.3) for HPV 16, 11.7 (2-37.7) for HPV 18, 20 (3.5-55.7) for HPV 31, 11.1 (0.6-49.3) for HPV 51, 12.5 (0.6-53.3) for HPV 58 and 59. CONCLUSION: We showed the relative high PPV for CIN2+ in OHrHPV other than HPV 16/18 positive group among cytology negative population. HPV 33, 51, 58, 59 and 18 had similar PPV for CIN2+ in basal cytology negative population.

Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer.

Persistent HPV (Human Papillomavirus) infection is the primary cause of cervical cancer. Despite the development of the HPV vaccine to prevent infections, cervical cancer is still a fatal malignant tumor and metastatic disease, and it is often difficult to treat, so a new treatment strategy is needed. The FDA-approved drug Bazedoxifene is a novel inhibitor of protein-protein interactions between IL-6 and GP130. Multiple ligand simultaneous docking and drug repositioning approaches have demonstrated that an IL-6/GP130 inhibitor can act as a selective estrogen modulator. However, the molecular basis for GP130 activation in cervical cancer remains unclear. In this study, we investigated the anticancer properties of Bazedoxifene in HPV-positive cervical cancer cells. In vitro and in vivo experiments showed that Bazedoxifene inhibited cell invasion, migration, colony formation, and tumor growth in cervical cancer cells. We also confirmed that Bazedoxifene inhibits the GP130/STAT3 pathway and suppresses the EMT (Epithelial-mesenchymal transition) sub-signal. Thus, these data not only suggest a molecular mechanism by which the GP130/STAT3 pathway may promote cancer, but also may provide a basis for cervical cancer replacement therapy.

Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway

Background/aim: Lycopene is associated with anticancer effects in various tumor types. However, the exact underlying mechanisms of action of lycopene in human cervical cancer remain to be determined. This study aimed to determine anticancer efficacy and mechanism of lycopene in human cervical carcinoma (HeLa) cells. Materials and methods: HeLa cells were treated with cisplatin (1 µM) alone, lycopene (10 µM) alone, and in combination for 72 h. The cell viability of HeLa cells was assessed via MTS assay. Western blot was used to analyze the expression levels of the nuclear factor-kappa B (NF-κB), B-cell-associated X protein (Bax), nuclear factor erythroid 2-related factor (Nrf2), and B-cell lymphoma 2 (Bcl-2). Results: We found that lycopene acts as a synergistic agent with cisplatin in preventing the growth of HeLa cells. The rates of HeLa cells' viability were 65.6% and 71.1% with lycopene and cisplatin treatment alone compared to the control group, respectively (P < 0.001). The inhibitory effect of cisplatin was enhanced with lycopene addition by declining the cell viability to 37.4% (P < 0.0001). Lycopene treatment significantly increased Bax expression (P < 0.0001) and decreased Bcl-2 expression (P < 0.0001) in HeLa cells. Furthermore, lycopene markedly activated the Nrf2 expression (P < 0.001) and suppressed the NF-κB signaling pathway (P < 0.0001). Conclusion: Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, the anticancer effect of lycopene might be also associated with suppression of NF-κB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer.

Recycling the Interspecific Relations with Epithelial Cells: Bacteria and Cancer Metabolic Symbiosis.

Several aspects of the human physiology are controlled by the microbiota that plays a key role in health and disease. In fact, microbial dysbiosis is associated with numerous diseases, including several types of cancer such as colon, gastric, esophageal, pancreatic, laryngeal, breast and gallbladder carcinomas.Metabolic symbiosis between non-malignant cells and the resident microbita is crucial for the host homeostasis. However, cancer cells are able to repurpose the pre-existing metabolic symbiosis, being able to recycle those relations and also create novel metabolic symbiosis, leading to profound alterations on the local microenvironment.In here we will explore some of these symbiotic metabolic interactions between bacteria and non-malignant cells in two different contexts: colon and uterine cervix. The way malignant cells are able to recycle these normal interactions and also create novel types of symbiotic metabolic relations will also be discussed.The knowledge of these complex interactions and recycling mechanisms is of extreme importance for cancer treatment, as new therapeutic targets could be developed.

Production and antiproliferative effect of violacein, a purple pigment produced by an Antarctic bacterial isolate.

We studied the production and the potential use of a purple-pigment produced by an Antarctic bacterial isolate. This pigment was identified as violacein, a metabolite produced by many bacterial strains and reported that it has antiproliferative activity in many cell lines. We analyzed the effect of temperature and the composition of the growth medium on pigment production, achieving the highest yield at 20 °C in Tryptic Soy Broth medium supplemented with 3.6 g/L glucose. We doubled the yield of the pigment production when the process was scaled up in a 5 L bioreactor (77 mg/L of crude pigment). The pigment was purified and identified by mass spectrometry (DI-EI-MS) and Nuclear Magnetic Resonance (NMR) spectroscopy as violacein. We performed survival assays that showed that the pure pigment has antiproliferative activity and sensitize HeLa cells (cervix cell carcinoma) to cisplatin. Besides, the pigment did not show genotoxic activity in HeLa cells as found performing micronucleus assays. These results suggest that this pigment may be used as anticancer or sensitizer to cisplatin drug in cervix cancer.

[Cutaneous metastasis in cervix cancer]. / L'image du mois. Métastases cutanées secondaires à un cancer du col de l'utérus.

Cutaneous metastases from cervix cancer are rarely described, and can appear years after a complete remission of the cancer. They may have multiple presentation as nodules, papules or telangiectasies. Unfortunately, these are associated with poor prognosis. We here report the case of a woman who developed cutaneous metastasis in the situation of a cervix cancer that appears to be stable under bevacizumab.

Les métastases cutanées provenant du cancer du col de l'utérus sont rarement décrites, et peuvent apparaître plusieurs années après une rémission complète du cancer. Elles peuvent avoir plusieurs types de présentations telles que : nodules, papules, télangiectasies. Malheureusement, ces dernières sont associées à un mauvais pronostic. Nous rapportons le cas d'une patiente qui a développé des métastases cutanées alors que son cancer primitif était stable sous traitement par bévacizumab.

Significant impact on the oncologic outcomes with intensity modulated radiotherapy and conformational radiotherapy over conventional radiotherapy in cervix cancer patients treated with radiotherapy.

OBJECTIVE: We designed a retrospective cohort of women with cervix cancer treated by radiation therapy with an extended follow-up to evaluate if the incorporation of modern radiation techniques was a prognostic factor. MATERIAL AND METHODS: We studied a cohort of patients with cervix cancer FIGO stage I-IVa treated in the last fifteen years. Patients were treated with radiotherapy alone (RT) or chemoradiation alone (CRT) using conventional radiotherapy (2DRT), conformational radiotherapy (3DRT), or intensity-modulated radiotherapy (IMRT) followed by high dose rate brachytherapy. Univariate and multivariate analysis was conducted to identify significant prognostic factors (p < 0.05). RESULTS: 228 patients with cervix cancer were included. The treatment groups were CRT (64.8%), and RT (34.2%), with 31.6% submitted to 2DRT and 68.4% to IMRT/3DRT. The median follow-up was 6.3 years, the OS in 5 years according to the treatment groups was 48% for CRT, and 27.8% for RT (p < 0.001). The early-stage I-IIa (p = 0.001), CRT, and IMRT/3DRT were significant factors for better overall survival (OS) in the multivariate analysis. For the cancer-specific survival (CSS), chemoradiation, age <60 years, and IMRT/3DRT were significant. Treatment with IMRT/3DRT was the only prognostic factor associated with event-free survival (EFS). CONCLUSION: In a long-term follow-up, chemoradiation, early-clinical stage, and age <60 years were significant factors associated with better OS and CSS at 5 and 8 years. The incorporation of new radiation techniques, such as IMRT/3DRT, over time has a significant impact on all endpoints (EFS, OS, and CSS) of this cohort. These outcomes are useful to decide about the radiation technique to achieve satisfactory oncological results outside a clinical trial.