Pain management in cervical cancer.

Cervical cancer (CC) occupies the second place in incidence and mortality among women in México. Despite this, Cervical Cancer continues to have a late diagnosis which leads to a high rate of complications. Pain represents the most feared and disabling symptom, being present in up to 86% of patients with advanced disease. The approach to managing pain in this population has not been studied and described to a full extent. In addition, there is a pressing need to provide concise recommendations to promote adequate pain control. We performed a review of the literature in CC and had experts in the field of pain management evaluate the evidence found. We then issued relevant recommendations on pharmacology and interventional pain management. Thus, the approach to pain management must be comprehensive and individualized, considering the timely and appropriate use of pharmacologic treatment as well as interventional procedures.

Human gastrin- releasing peptide receptor expression in women with uterine cervix cancer.

Introduction: 212Pb-DOTAM-GRPR1 is a pharmaceutical radioimmunoconjugate consisiting of an α-particle-emitting radionuclide lead-212 (212Pb), a metal chelator DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane), and a gastrin-releasing peptide receptor (GRPR)-targeted antagonist currently being evaluated as therapy in uterine cervix and other cancer types. Previous studies have revealed that a variable proportion of uterine cervix cancer tumors overexpress the radiopharmaceutical target GRPR when assessed by cell proportion and staining intensity immunoreactive scores (IRS). Tumor response to 212Pb-DOTAM-GRPR1 strongly associates with GRPR overexpression, and therefore, it seems reasonable to assess uterine cervix cancer GRPR immunoreactivity for greater insight into the feasibility of using 212Pb-DOTAM-GRPR1 as a radiopharmaceutical treatment. Methods: We examined a series of 33 uterine cervix cancer paraffin-embedded tumors in order to establish whether this tumor type overexpresses GRPR at an IRS score of 6 or higher, as 212Pb-DOTAM-GRPR1 is currently being evaluated in clinical trials against tumors showing such a level of expression. Results: The results show that five of five (100%) primary adenocarcinomas and 10 of 16 (63%) primary squamous cell tumors overexpress GRPR at an IRS score of 6 or higher. Discussion: The frequency of overexpression in this study suggests that 212Pb-DOTAM-GRPR1 radiopharmaceutical treatment may be useful in the management of persistent, recurrent, or metastatic uterine cervix cancer patients. A phase I clinical trial involving patients with metastatic uterine cervix cancer is currently underway (NCT05283330).

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.

Unsupervised Deep Learning Registration of Uterine Cervix Sequence Images.

During a colposcopic examination of the uterine cervix for cervical cancer prevention, one or more digital images are typically acquired after the application of diluted acetic acid. An alternative approach is to acquire a sequence of images at fixed intervals during an examination before and after applying acetic acid. This approach is asserted to be more informative as it can capture dynamic pixel intensity variations on the cervical epithelium during the aceto-whitening reaction. However, the resulting time sequence images may not be spatially aligned due to the movement of the cervix with respect to the imaging device. Disease prediction using automated visual evaluation (AVE) techniques using multiple images could be adversely impacted without correction for this misalignment. The challenge is that there is no registration ground truth to help train a supervised-learning-based image registration algorithm. We present a novel unsupervised registration approach to align a sequence of digital cervix color images. The proposed deep-learning-based registration network consists of three branches and processes the red, green, and blue (RGB, respectively) channels of each input color image separately using an unsupervised strategy. Each network branch consists of a convolutional neural network (CNN) unit and a spatial transform unit. To evaluate the registration performance on a dataset that has no ground truth, we propose an evaluation strategy that is based on comparing automatic cervix segmentation masks in the registered sequence and the original sequence. The compared segmentation masks are generated by a fine-tuned transformer-based object detection model (DeTr). The segmentation model achieved Dice/IoU scores of 0.917/0.870 and 0.938/0.885, which are comparable to the performance of our previous model in two datasets. By comparing our segmentation on both original and registered time sequence images, we observed an average improvement in Dice scores of 12.62% following registration. Further, our approach achieved higher Dice and IoU scores and maintained full image integrity compared to a non-deep learning registration method on the same dataset.

Lifetime radiation-induced sarcoma risk in patients subjected to IMRT or VMAT for uterine cervix carcinoma.

This study was conducted to estimate the lifetime radiation-induced bone and soft tissue sarcoma risks from intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for uterine cervix carcinoma. 13 cervical cancer patients were included. The bone and soft tissue structures were defined on patients' treatment planning computed tomography (CT) scans. Both CT-based IMRT and VMAT plans with 6 MV photons delivering 45 Gy to the target site were designed for each patient. The organ equivalent dose (OED) and the lifetime attributable risk (LAR) for developing bone or soft tissue sarcoma were estimated using treatment planning data and a non-linear mechanistic model. The estimation method did not consider the survival rates following radiotherapy and the use of brachytherapy treatments. The patient-specific OEDs of the bone structure from IMRT and VMAT were 2.33-2.83 and 2.34-2.82 Gy, respectively. The corresponding values for the soft tissue structure were 1.27-1.70 and 1.32-1.73 Gy. An insignificant difference was found between the patient-specific OEDs and the directly proportional sarcoma risks (bone: P = 0.07; soft tissue: P = 0.38). The LAR for the development of a bone sarcoma varied from 0.05 to 0.16% by the patient's age during irradiation and the applied treatment delivery technique. The corresponding LAR range for radiation-induced soft-tissue sarcoma was 0.08-0.27%. The above LARs resulted in a relative risk of more than 1.20 indicating that IMRT or VMAT may lead to a considerable risk increase of developing bone or soft tissue sarcoma exceeding 20% in respect to the current incidence of these malignancies in unexposed population.

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.

The Stacked-Ellipse Algorithm: An Ultrasound-Based 3-D Uterine Segmentation Tool for Enabling Adaptive Radiotherapy for Uterine Cervix Cancer.

The stacked-ellipse (SE) algorithm was developed to rapidly segment the uterus on 3-D ultrasound (US) for the purpose of enabling US-guided adaptive radiotherapy (RT) for uterine cervix cancer patients. The algorithm was initialised manually on a single sagittal slice to provide a series of elliptical initialisation contours in semi-axial planes along the uterus. The elliptical initialisation contours were deformed according to US features such that they conformed to the uterine boundary. The uterus of 15 patients was scanned with 3-D US using the Clarity System (Elekta Ltd.) at multiple days during RT and manually contoured (n = 49 images and corresponding contours). The median (interquartile range) Dice similarity coefficient and mean surface-to-surface-distance between the SE algorithm and manual contours were 0.80 (0.03) and 3.3 (0.2) mm, respectively, which are within the ranges of reported inter-observer contouring variabilities. The SE algorithm could be implemented in adaptive RT to precisely segment the uterus on 3-D US.

Randomized Phase II Trial of Triapine-Cisplatin-Radiotherapy for Locally Advanced Stage Uterine Cervix or Vaginal Cancers.

Uterine cervix or vaginal cancers have inherent overactivity of ribonucleotide reductase (RNR), making these cancers rational targets for therapy based on interruption of cisplatin-radiotherapy-induced DNA damage repair. We conducted a pilot, open-label randomized phase II trial to evaluate the efficacy and safety of cisplatin-radiotherapy with or without triapine, a small molecule with RNR-inhibitory activity, in patients with advanced-stage uterine cervix or vaginal cancers (NCT01835171), as a lead in to a randomized phase III study (NCT02466971). A total of 26 women were randomly assigned to receive 6 weeks of daily radiotherapy followed by brachytherapy (80 Gy) and once-weekly cisplatin (40 mg m-2)-with or without three-times weekly intravenous triapine (25 mg m-2)-in one 56-days cycle. Primary end points were metabolic complete response by positron emission tomography and safety. Additional end points included the rate of clinical response, rate of methemoglobinemia, and progression-free survival. The addition of triapine to cisplatin-radiotherapy improved the rate of metabolic complete response from 69 to 92% (P = 0.32) and raised the 3-year progression-free survival estimate from 77 to 92% (hazard ratio for progression, 0.30; P = 0.27). The most frequent grade 3 or 4 adverse events in either treatment group included reversible leukopenia, neutropenia, fatigue, or electrolyte abnormalities. No significant differences were seen between the two groups in the rate of adverse events. Symptomatic methemoglobinemia was not encountered after triapine infusion. In conclusion, the addition of triapine to cisplatin-radiotherapy improved the rate of metabolic complete response in patients with advanced-stage uterine cervix or vaginal cancers without significant toxicity. A phase III trial adequately powered to evaluate progression-free and overall survival is underway (NCT02466971).

Radiopharmaceuticals for Persistent or Recurrent Uterine Cervix Cancer.

Uterine cervix cancers pose therapeutic challenges because of an overactive ribonucleotide reductase, which provides on-demand deoxyribonucleotides for DNA replication or for a DNA damage repair response. Ribonucleotide reductase overactivity bestows cancer cell resistance to the effects of radiotherapy and chemotherapy used to treat disease; but nevertheless, this same biologic overexpression provides opportune vulnerabilities relatively specific to uterine cervix cancers for new therapeutic strategies to take advantage. The discovery of human epidermal growth factor receptor 2 (ErbB2 or HER2) overexpression on metastatic uterine cervix cancer cells provides an opportunity for clinical trials of targeted radiopharmaceuticals in combination with DNA damage response modifying drugs. The National Cancer Institute's clinical trial infrastructure and its experimental therapeutics portfolio can now offer clinical trial evaluation of molecularly-targeted and tolerated radiopharmaceutical-drug combinations for women with persistent or recurrent metastatic uterine cervix cancer. This article discusses the current thinking of the National Cancer Institute in regard to attractive radiopharmaceutical strategies for this disease and others.

Leveraging National Cancer Institute Programmatic Collaboration for Uterine Cervix Cancer Brachytherapy in Puerto Rico After Hurricane Maria.

Evaluating the impact of natural disasters on cancer patients is vital to the recovery of cancer treatment services and infrastructure. In September 2017, Hurricane Maria demolished the gynecologic cancer service in the United States territory of Puerto Rico and its outreach to the territory of the Virgin Islands of the United States. Patient access to brachytherapy for uterine cervix cancer patients can be difficult to measure in the aftermath of a hurricane. The United States National Cancer Institute (NCI) surveyed gynecologic radiation medicine providers on the island to generate an independent perspective on gynecologic brachytherapy service recovery after the hurricane. Providers were asked about patient displacement, infrastructure loss, and reestablishment of cancer treatment. Here, the NCI provides its perspective on recovery of these services as it relates to its pre-hurricane investment for staff in the NCI Community Oncology Research Program.

Magnetic resonance imaging after external beam radiotherapy and concurrent chemotherapy for locally advanced cervical cancer helps to identify patients at risk of recurrence.

OBJECTIVE: Tumor volume and regression after external beam radiotherapy have been shown to be accurate parameters to assess treatment response via magnetic resonance imaging (MRI). The aim of the study was to evaluate the prognostic value of tumor size reduction rate after external beam radiotherapy and chemotherapy prior to brachytherapy. METHODS: Patients with locally advanced cervical cancer treated at two French comprehensive cancer centers between 1998 and 2010 were included. Treatment was pelvic external beam radiotherapy with platinum based chemotherapy followed by brachytherapy. Records were reviewed for demographic, clinical, imaging, treatment, and follow-up data. Anonymized linked data were used to ascertain the association between pre-external and post-external beam radiotherapy MRI results, and survival data. RESULTS: 185 patients were included in the study. Median age at diagnosis was 45 years (range 26-72). 77 patients (41.6%) were International Federation of Gynecology and Obstetrics stage IB2-IIA disease and 108 patients (58.4%) were stage IIB-IVA. Median tumor size after external beam radiotherapy and chemotherapy was 2.0 cm (range 0.0-8.0) and median tumor size reduction rate was 62.4% (range 0.0-100.0%). Tumor size and tumor reduction rate at 45 Gy external beam radiotherapy MRI were significantly associated with local recurrence free survival (P<0.001), disease free survival, and overall survival (P<0.05). Tumor reduction rate ≥60% was significantly associated with a decreased risk of relapse and death (HR (95% CI) 0.21 (0.09 to 0.50), P=0.001 for local recurrence free survival; 0.48 (0.30 to 0.77) P=0.002 for disease free survival; and 0.51 (0.29 to 0.88), P=0.014 for overall survival). CONCLUSIONS: Tumor size reduction rate >60% between pre-therapeutic and post-therapeutic 45 Gy external beam radiotherapy with concurrent chemotherapy was associated with improved survival. Future studies may help to identify patients who may ultimately benefit from completion surgery, adjuvant chemotherapy, and closer follow-up.

A survival study of uterine cervical patients in the North East India: Hospital-cancer registry-based analysis.

BACKGROUND: Uterine cervical cancer constitutes a major proportion of cancer in females of our population. The objective of this study was to conduct a clinical study of uterine cervical cancers including their survival from hospital-cancer registry data. MATERIALS AND METHODS: Data of uterine cervical cancer patients diagnosed from January 1, 2010 to December 31, 2010 and that were treated at a regional cancer center in North East (NE) India was recruited. The cases were analyzed for age group distribution, stage, and treatment types. Survival from the date of first diagnosis and hazard ratios (HRs) was estimated. Survival probability and HRs were calculated by Kaplan-Meier method and Cox-proportional regression analysis, respectively. Active follow-up was done for the survival analysis. RESULTS: One hundred and ninety-three patients (53.4%) were included for the analysis. Median age was 48 years, 56.5% (108/193) of patients were in the age group of 45-64 years, 56.5% (109/193) were Stage II patients, radiotherapy alone was the main treatment modality in 65.8% (127/193) of cases, 5-year overall survival (OS) was 40.7%, median survival was 44 months, early staged and advanced stage patients had 47.7%, and 29.4% 5-year OS (P = 0.002), respectively, and HR for advanced stages was 1.8 (P = 0.003, confidence interval (CI) = 1.2 to 2.7). CONCLUSION: Describing the clinical characteristics and survival of uterine cervical cancer patients is important for planning and identifying the gaps for its control in the NE India.

Triapine Radiochemotherapy in Advanced Stage Cervical Cancer.

Clinical ribonucleotide reductase (RNR) inhibitors have reinvigorated enthusiasm for radiochemotherapy treatment of patients with regionally advanced stage cervical cancers. About two-thirds of patients outlive their cervical cancer (1), even though up to half of their tumors retain residual microscopic disease (2). The National Cancer Institute Cancer Therapy Evaluation Program conducted two prospective trials of triapine-cisplatin-radiation to improve upon this finding by precisely targeting cervical cancer's overactive RNR. Triapine's potent inactivation of RNR arrests cells at the G1/S cell cycle restriction checkpoint and enhances cisplatin-radiation cytotoxicity. In this article, we provide perspective on challenges encountered in and future potential of clinical development of a triapine-cisplatin-radiation combination for patients with regionally advanced cervical cancer. New trial results and review presented here suggest that a triapine-cisplatin-radiation combination may offer molecular cell cycle target control to maximize damage in cancers and to minimize injury to normal cells. A randomized trial now accrues patients with regionally advanced stage cervical cancer to evaluate triapine's contribution to clinical benefit after cisplatin-radiation (clinicaltrials.gov, NCT02466971).

Leveraging National Cancer Institute Programmatic Collaboration for Uterine Cervix Cancer Patient Accrual in Puerto Rico.

Women in the U.S. Commonwealth of Puerto Rico (PR) have a higher age-adjusted incidence rate for uterine cervix cancer than the U.S. mainland as well as substantial access and economic barriers to cancer care. The National Cancer Institute (NCI) funds a Minority/Underserved NCI Community Oncology Research Program in PR (PRNCORP) as part of a national network of community-based health-care systems to conduct multisite cancer clinical trials in diverse populations. Participation by the PRNCORP in NCI's uterine cervix cancer clinical trials, however, has remained limited. This study reports on the findings of an NCI site visit in PR to assess barriers impeding site activation and accrual to its sponsored gynecologic cancer clinical trials. Qualitative, semi-structured individual, and group interviews were conducted at six PRNCORP-affiliated locations to ascertain: long-term trial accrual objectives; key stakeholders in PR that address uterine cervix cancer care; key challenges or barriers to activating and to enrolling patients in NCI uterine cervix cancer treatment trials; and resources, policies, or procedures in place or needed on the island to support NCI-sponsored clinical trials. An NCI-sponsored uterine cervix cancer radiation-chemotherapy intervention clinical trial (NCT02466971), already activated on the island, served as a test case to identify relevant patient accrual and site barriers. The site visit identified five key barriers to accrual: (1) lack of central personnel to coordinate referrals for treatment plans, medical tests, and medical imaging across the island's clinical trial access points; (2) patient insurance coverage; (3) lack of a coordinated brachytherapy schedule at San Juan-centric service providers; (4) limited credentialed radiotherapy machines island-wide; and (5) too few radiology medical physicists tasked to credential trial-specified positron emission tomography scanners island-wide. PR offers a unique opportunity to study overarching and tactical strategies for improving accrual to NCI-sponsored gynecologic cancer clinical trials. Interview findings support adding and re-tasking personnel for coordinated trial-eligible patient referral, accrual, and treatment.

Asociación entre polimorfismos de Glutation s-transferasa y cáncer cérvico uterino / Association between polymorphisms of Glutathione s-transferase and cervical cancer

Introducción: entre los factores de riesgo que favorecen la aparición de las lesiones cérvico uterinas, se encuentran la infección por virus de papiloma humano, la promiscuidad, el uso de anticonceptivos orales y el hábito de fumar. No obstante, varias investigaciones refieren que los polimorfismos genéticos podrían contribuir al desarrollo y progresión del cáncer cérvico uterino. Objetivo: identificar en la bibliografía revisada, la frecuencia de asociación de los polimorfismos de Glutation s - transferasa con el cáncer cérvico uterino y con factores de riesgo que inciden en la patología. Métodos: se realizó una extensa revisión de la literatura especializada a través de los buscadores en base de datos de PubMed, EBSCO, NCBI y BVS. Resultados: se constató la variabilidad en los reportes de las frecuencias alélicas de los genotipos GSTM1 y T1 en distintas poblaciones. Se corroboró en varios estudios revisados el hallazgo de asociación entre los genotipos GSTM1 y T1 nulos y cáncer cérvico uterino y, de igual forma con el consumo de tabaco y anticonceptivos orales por tiempo prolongado. Conclusiones: la bibliografía sobre el tema pone en evidencia que los genes que codifican la enzima Glutation s - transferasa intervienen en la protección celular contra los efectos citotóxicos, de manera que cuando éstos presentan alteración se afecta la actividad enzimática, lo que predispone a una mayor susceptibilidad al cáncer(AU)

Introduction: Among risk factors that lead to uterine cervix lesions we can find the human papilloma virus infection, promiscuity, use of oral contraceptive and smoking habit. However, several researches refer that genetic polymorphism could be related to the development and progression of the uterine cervix cancer. Objective: Identify the association of glutathione S- transferases polymorphism with uterine cervix cancer and risk factors relate with this disease, in the revise bibliography. Method: An extensive review was made of the specialized literature using web search in database PubMed, EBSCO, NCBI and BVS. Result: The variability of the allelic frequency of the GSTM1 and T1 genotypes in different populations was confirmed. Besides the association between null GSTM1 and T1 with uterine cervix cancer was corroborated. In addition, this association with smoking habit and the use of oral contraceptive for long time was corroborated. Conclusions: Consulted bibliography shows that genes encoding glutahione S- transferases enzyme contribute to the cellular protection against cytotoxic effects, therefore, alterations in these genes affect the enzymatic activity lead to a major susceptibility to suffer cancer(AU)

Asociación entre polimorfismos de Glutation s-transferasa y cáncer cérvico uterino / Association between polymorphisms of Glutathione s-transferase and cervical cancer

Introducción: entre los factores de riesgo que favorecen la aparición de las lesiones cérvico uterinas, se encuentran la infección por virus de papiloma humano, la promiscuidad, el uso de anticonceptivos orales y el hábito de fumar. No obstante, varias investigaciones refieren que los polimorfismos genéticos podrían contribuir al desarrollo y progresión del cáncer cérvico uterino. Objetivo: identificar en la bibliografía revisada, la frecuencia de asociación de los polimorfismos de Glutation s - transferasa con el cáncer cérvico uterino y con factores de riesgo que inciden en la patología. Métodos: se realizó una extensa revisión de la literatura especializada a través de los buscadores en base de datos de PubMed, EBSCO, NCBI y BVS. Resultados: se constató la variabilidad en los reportes de las frecuencias alélicas de los genotipos GSTM1 y T1 en distintas poblaciones. Se corroboró en varios estudios revisados el hallazgo de asociación entre los genotipos GSTM1 y T1 nulos y cáncer cérvico uterino y, de igual forma con el consumo de tabaco y anticonceptivos orales por tiempo prolongado. Conclusiones: la bibliografía sobre el tema pone en evidencia que los genes que codifican la enzima Glutation s - transferasa intervienen en la protección celular contra los efectos citotóxicos, de manera que cuando éstos presentan alteración se afecta la actividad enzimática, lo que predispone a una mayor susceptibilidad al cáncer(AU)

Introduction: Among risk factors that lead to uterine cervix lesions we can find the human papilloma virus infection, promiscuity, use of oral contraceptive and smoking habit. However, several researches refer that genetic polymorphism could be related to the development and progression of the uterine cervix cancer. Objective: Identify the association of glutathione S- transferases polymorphism with uterine cervix cancer and risk factors relate with this disease, in the revise bibliography. Method: An extensive review was made of the specialized literature using web search in database PubMed, EBSCO, NCBI and BVS. Result: The variability of the allelic frequency of the GSTM1 and T1 genotypes in different populations was confirmed. Besides the association between null GSTM1 and T1 with uterine cervix cancer was corroborated. In addition, this association with smoking habit and the use of oral contraceptive for long time was corroborated. Conclusions: Consulted bibliography shows that genes encoding glutahione S- transferases enzyme contribute to the cellular protection against cytotoxic effects, therefore, alterations in these genes affect the enzymatic activity lead to a major susceptibility to suffer cancer(AU)

Phase I Trial of Triapine-Cisplatin-Paclitaxel Chemotherapy for Advanced Stage or Metastatic Solid Tumor Cancers.

Ribonucleotide reductase (RNR) is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine is a small-molecule RNR inhibitor. A phase I trial studied the safety of triapine in combination with cisplatin-paclitaxel in patients with advanced stage or metastatic solid tumor cancers in an effort to capitalize on disrupted DNA damage repair. A total of 13 patients with various previously treated cancers were given a 96-h continuous intravenous (i.v.) infusion of triapine (40-120 mg/m2) on day 1, and then 3-h i.v. paclitaxel (80 mg/m2) followed by 1-h i.v. cisplatin (50-75 mg/m2) on day 3. This combination regimen was repeated every 21 days. The maximum tolerated dose (MTD) for each agent was identified to be triapine (80 mg/m2), cisplatin (50 mg/m2), and paclitaxel (80 mg/m2). Common grade 3 or 4 toxicities included reversible anemia, leukopenia, thrombocytopenia, or electrolyte abnormalities. The combination regimen of triapine-cisplatin-paclitaxel resulted in no objective responses; however, five (83%) of six patients treated at the MTD had stable disease between 1 and 8 months duration. This phase I study showed that the combination regimen of triapine-cisplatin-paclitaxel was safe and provides a rational basis for a follow-up phase II trial to evaluate efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.

Differences in the outcomes and complications between elderly and younger uterine cervical cancer patients treated by definitive radiotherapy - A propensity score-matched study.

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.

Monitoring of organochlorine pesticides in blood of women with uterine cervix cancer.

In Yucatan, Mexico, chronic exposure of Mayan population to pesticides is expected as about 30 per cent are drinking polluted water. Residues of organochlorine pesticides (OCP) were monitored in 18 municipalities of Yucatan with high mortality rates due to uterine cervix cancer. 70 blood samples collected from Mayan women living in livestock, agricultural and metropolitan area were analyzed for OCP. Solid Phase Extraction was performed on C18 cartridges and analyzed by Gas Chromatography with Electron Capture Detector. The results showed that the highest OCP levels were detected in blood of women living in the livestock area. OCP detected were endosulfan I (7.35 µg/mL), aldrin (3.69 µg/mL), 4,4' DDD (2.33 µg/mL), 1.39 and 1.46 µg/mL of δ-HCH. Women from the agricultural area had high concentrations of OCP in their blood, particularly dieldrin (1.19 µg/mL), and 1.26 µg/mL of 4,4' DDE. In the metropolitan area, 0.080 µg/mL of γ-HCH and 0.064 µg/mL of heptachlore were detected. This monitoring study was also based on epidemiological data of uterine cervical cancer. It was found that environmental factors may have facilitated the infiltration of OCP to the aquifer used for potable water supply. These factors in addition to poverty can have impacts on public health. This first exploratory study suggests that monitoring of OCP in human is important for the establishment of health promotion programs. The integrative analysis of both, environmental and social factors would be helpful to characterize the bioaccumulation of pesticides in humans.