17-ß Estradiol up-regulates energy metabolic pathways, cellular proliferation and tumor invasiveness in ER+ breast cancer spheroids.

Several biological processes related to cancer malignancy are regulated by 17-ß estradiol (E2) in ER+-breast cancer. To establish the role of E2 on the atypical cancer energy metabolism, a systematic study analyzing transcription factors, proteins, and fluxes associated with energy metabolism was undertaken in multicellular tumor spheroids (MCTS) from human ER+ MCF-7 breast cancer cells. At E2 physiological concentrations (10 and 100 nM for 24 h), both ERα and ERß receptors, and their protein target pS2, increased by 0.6-3.5 times vs. non-treated MCTS, revealing an activated E2/ER axis. E2 also increased by 30-470% the content of several transcription factors associated to mitochondrial biogenesis and oxidative phosphorylation (OxPhos) (p53, PGC1-α) and glycolytic pathways (HIF1-α, c-MYC). Several OxPhos and glycolytic proteins (36-257%) as well as pathway fluxes (48-156%) significantly increased being OxPhos the principal ATP cellular supplier (>75%). As result of energy metabolism stimulation by E2, cancer cell migration and invasion processes and related proteins (SNAIL, FN, MM-9) contents augmented by 24-189% vs. non-treated MCTS. Celecoxib at 10 nM blocked OxPhos (60%) as well as MCTS growth, cell migration and invasiveness (>40%); whereas the glycolytic inhibitor iodoacetate (0.5 µM) and doxorubicin (70 nM) were innocuous. Our results show for the first time using a more physiological tridimensional cancer model, resembling the initial stages of solid tumors, that anti-mitochondrial therapy may be useful to deter hormone-dependent breast carcinomas.

Ibero-American Expert Consensus on Squamous Cell Carcinoma of the Head and Neck Treatment in Patients Unable to Receive Cisplatin: Recommendations for Clinical Practice.

Cisplatin is the standard of treatment for squamous cell carcinoma of the head and neck (SCCHN) that has demonstrated efficacy, either in locally advanced disease when combined with radiotherapy at high doses, or in metastatic/recurrent disease when combined with other agents. However, the usual toxicities related to cisplatin, such as neurotoxicity, nephrotoxicity, ototoxicity, and hematologic toxicities, especially when high doses have been administered, have important implications in the patients' quality of life. The decision to administer cisplatin depends on several patient factors, such as age, performance status, weight loss, comorbidities, previous toxicities, chronic viral infection, or even the current SARS-CoV-2 pandemic. In order to establish recommendations for the management of patients with SCCHN, a group of experts in medical and radiation oncology from Spain and Latin-American discussed how to identify patients who are not candidates for cisplatin to offer them the most suitable therapeutic alternative.

Acetate Promotes a Differential Energy Metabolic Response in Human HCT 116 and COLO 205 Colon Cancer Cells Impacting Cancer Cell Growth and Invasiveness.

Under dysbiosis, a gut metabolic disorder, short-chain carboxylic acids (SCCAs) are secreted to the lumen, affecting colorectal cancer (CRC) development. Butyrate and propionate act as CRC growth inhibitors, but they might also serve as carbon source. In turn, the roles of acetate as metabolic fuel and protein acetylation promoter have not been clearly elucidated. To assess whether acetate favors CRC growth through active mitochondrial catabolism, a systematic study evaluating acetate thiokinase (AcK), energy metabolism, cell proliferation, and invasiveness was performed in two CRC cell lines incubated with physiological SCCAs concentrations. In COLO 205, acetate (+glucose) increased the cell density (50%), mitochondrial protein content (3-10 times), 2-OGDH acetylation, and oxidative phosphorylation (OxPhos) flux (36%), whereas glycolysis remained unchanged vs. glucose-cultured cells; the acetate-induced OxPhos activation correlated with a high AcK activity, content, and acetylation (1.5-6-fold). In contrast, acetate showed no effect on HCT116 cell growth, OxPhos, AcK activity, protein content, and acetylation. However, a substantial increment in the HIF-1α content, HIF-1α-glycolytic protein targets (1-2.3 times), and glycolytic flux (64%) was observed. Butyrate and propionate decreased the growth of both CRC cells by impairing OxPhos flux through mitophagy and mitochondrial fragmentation activation. It is described, for the first time, the role of acetate as metabolic fuel for ATP supply in CRC COLO 205 cells to sustain proliferation, aside from its well-known role as protein epigenetic regulator. The level of AcK determined in COLO 205 cells was similar to that found in human CRC biopsies, showing its potential role as metabolic marker.

Patients' quality of life: Validation of the functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) instrument for the Mexican population.

OBJECTIVE: The functional assessment of cancer therapy-bone marrow transplant (FACT-BMT) is a widely used instrument to assess quality of life (QOL) in hematopoietic stem cell transplant (HSCT) patients, but there is little evidence of its validity in Latin American populations. This study evaluated the psychometric properties of the Spanish language version of the FACT-BMT in Mexican patients. METHOD: First, the original version was piloted with 15 HSCT patients to obtain an adequate cultural version, resulting in the adaptation of one item. After that, the new version was completed by 139 HSCT patients. RESULTS: The results showed a FACT factor structure that explains 70.84% of the total variance, a factor structure similar to the original FACT structure, and with a high internal consistency (Cronbach's alpha = 0.867). For the BMT subscale, the best factor structure included 17 items which explain 61.65% of the total variance with an adequate internal consistency (Cronbach's alpha = 0.696). SIGNIFICANCE OF THE RESULTS: The FACT-BMT was found to be a valid and reliable instrument to evaluate QOL in Mexican patients. Our results constitute new FACT-BMT empirical evidence that supports its clinical and research uses.

Heart myxoma develops oncogenic and metastatic phenotype.

PURPOSE: Heart myxomas have been frequently considered as benign lesions associated with Carney's complex. However, after surgical removal, myxomas re-emerge causing dysfunctional heart. METHODS: To identify whether cardiac myxomas may develop a metastatic phenotype as occurs in malignant cancers, a profile of several proteins involved in malignancy such as oncogenes (c-MYC, K-RAS and H-RAS), cancer-associated metabolic transcriptional factors (HIF-1α, p53 and PPAR-γ) and epithelial-mesenchymal transition proteins (fibronectin, vimentin, ß-catenin, SNAIL and MMP-9) were evaluated in seven samples from a cohort of patients with atrial and ventricular myxomas. The analysis was also performed in: (1) cardiac tissue surrounding the area where myxoma was removed; (2) non-cancer heart tissue (NCHT); and (3) malignant triple negative breast cancer biopsies for comparative purposes. RESULTS: Statistical analysis applying univariate (Kruskal-Wallis and Dunn's tests) and multivariate analyses (PCA, principal component analysis) revealed that heart myxomas (7-15 times) and myxoma surrounding tissue (22-99 times) vs. NCHT showed high content of c-MYC, p53, vimentin, and HIF-1α, indicating that both myxoma and its surrounding area express oncogenes and malignancy-related proteins as occurs in triple negative breast cancer. CONCLUSIONS: Based on ROC (receiver operating characteristics) statistical analysis, c-MYC, HIF-1α, p53, and vimentin may be considered potential biomarkers for malignancy detection in myxoma.

Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma.

PURPOSE: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. METHODS: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. RESULTS: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. CONCLUSION: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

Epidemiological Data on the Nutritional Status of Cancer Patients Receiving Treatment with Concomitant Chemoradiotherapy, Radiotherapy or Sequential Chemoradiotherapy to the Abdominopelvic Area.

Cancer patients are particularly susceptible to undernourishment so associated weight loss is frequent. Approximately 15% of patients lose >10% of their usual body weight, 40-80% become undernourished, and about 20% die as a result. Well-nourished patients have a higher survival rate when compared with patients at risk of undernourishment (19.9 vs. 3.7 months); hence, nutritional intervention is pivotal. Undernourishment negatively influences the patient's prognosis, and its prevalence depends on the tumor type and location, disease stage, treatment, and the applied nutritional evaluation tool. During abdominopelvic radiotherapy, up to 90% of patients experience symptoms of varying severity; weight loss during radiotherapy is an early indicator of nutritional deterioration, and he the use of radiation is associated with a higher likelihood of undernourishment. In patients with gynecological malignancies, 12.5-54% are malnourished before receiving oncological treatment, worsening after treatment in 35.8-82% of cases. There is also deterioration of the nutritional status in patients with colorectal cancer once pelvic radiotherapy is initiated, whereby 50% of cases are malnourished at the beginning of treatment, and 66.7% are so when it ends. Although there are notable differences in the impact of radiotherapy on weight according to the radiated region, 88% patients receiving abdominal radiotherapy were found to lose weight compared to 38% of patients whose treatment was limited to the pelvis.

[Review of pharmacokinetic monitoring of 5-Fluorouracil as a tool to increase efficacy and safety]. / Revisión del monitoreo farmacocinético del 5-fluorouracilo como herramienta para incrementar eficacia y seguridad.

Recent progress in medical knowledge has indicated that both clinical and biological markers will determine the response to different medical treatments: age, gender and genetics will determine the success of treatment. Genetic variability in this respect is fundamental and determines efficiency and safety of drugs, as well as susceptibility and illness' development. Fortunately, personalized medicine now offers individually tailored treatment strategies for each patient's needs. This is of outmost importance in oncology, since treatment is per se toxic and the commonly found low serum drug concentrations result in low treatment efficacy. Personalized medicine will allow a better approach to this, until now, a poorly managed disease. In this review we intent to raise awareness of personalized medicine and of clinical pharmacologic monitoring, with the aim to achieve adequate levels of efficacy and safety in the use of the cytotoxic drug 5-Fluorouracil (5-FU). Additionally, the importance of pharmacogenomics for the use of 5-FU is discussed. We designed this discussion towards medical practitioners challenged with treatment decisions every day, together with their patients.

Los pacientes bajo tratamiento con alopurinol pueden presentar reacciones adversas potencialmente mortales, particularmente al inicio del tratamiento. Las reacciones cutáneas adversas por alopurinol tienen una prevalencia aproximada del 2 %. Presentamos dos casos de síndrome de hipersensibilidad por alopurinol en pacientes mexicanos en quienes la hiperuricemia asintomática fue la indicación para su uso. El médico general y el especialista deben estar alerta ante este síndrome que ocasiona alta morbilidad y mortalidad.

Advanced Squamous Cell Carcinoma of the Head and Neck: The Current Role of Cetuximab.

We review clinical trials of squamous cell carcinoma of the head and neck (SCCHN) to address the current and potential uses of cetuximab (CTX). PubMed was reviewed to identify papers published between 2010 and 2016. The search terms used were "cetuximab" and "head and neck cancer." A total of 634 articles were identified. Phase II or III studies with CTX in patients with advanced SCCHN without treatment or with recurrent/metastatic tumors were selected. Forty-six registries were obtained. Information was critically reviewed and relevant information presented. As definitive treatment of advanced squamous cells carcinomas and as palliative treatment of recurrent/metastatic disease, CTX alone or associated with chemotherapy and/or radiotherapy is an alternative to chemoradiotherapy because of its distinct and favorable toxicity profile.

Propiedades psicométricas de la Escala Hospitalaria de Ansiedad y Depresión (HADS) en una población de pacientes oncológicos mexicanos / Psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in a Mexican population of cancer patients

ANTECEDENTES: La sintomatología ansiosa y depresiva es parte de los principales problemas de salud mental en pacientes oncológicos, lo cual afecta la calidad de vida y la adhesión al tratamiento, además de que se asocia con mayor número de síntomas y estancia hospitalaria. Mediante instrumentos de tamizaje válidos y confiables, como la Escala hospitalaria de ansiedad y depresión (HADS), ha sido posible detectar posibles casos en pacientes hospitalarios. Sin embargo, hasta ahora no se habían caracterizado las propiedades psicométricas en pacientes oncológicos en población mexicana.OBJETIVO: Determinar las propiedades psicométricas de la HADS en una muestra de pacientes oncológicos.MÉTODO: Participaron 400 pacientes del Instituto Nacional de Cancerología, de los cuales 226 eran mujeres (56.5%) y 174 eran hombres (43.6%); la edad promedio fue de 47.4 ± 14.1 años. Los participantes contestaron, además de la HADS, los siguientes inventarios: depresión de Beck, ansiedad de Beck, termómetro de distrés.RESULTADOS: Un análisis factorial ajustado a dos factores presentó un instrumento con 12 reactivos, similar a la versión original. La consistencia interna de la escala global mostró un índice satisfactorio (a=0.86). Los alfas de Cronbach de cada subescala tuvieron un valor de .79 y .80 que explicaron el 48.04% de la varianza. La validez, por medio de correlación con las medidas concurrentes, mostró resultados significativos (r de Pearson de .51 a .71, p<0.05).DISCUSIÓN Y CONCLUSIÓN: La HADS en pacientes con cáncer en población mexicana presentó adecuadas características psicométricas. La relevancia de los resultados obtenidos radica en que se trata de una población que puede llegar a requerir atención oportuna en salud mental en etapas tempranas de su tratamiento. La detección de sintomatología ansiosa y depresiva por medio de la HADS deriva en beneficios para la población oncológica y en estrategias funcionales de atención adecuada y costo-efectivas.

BACKGROUND: Symptoms of anxiety and depression are among the major mental health problems in cancer patients. These symptoms affect the quality of life and treatment adherence, and are associated with other symptoms and longer hospital stays. Valid and reliable screening instruments such as the Hospital Anxiety and Depression Scale (HADS), have made possible the detection of possible cases of depression and anxiety in medically ill patients. However, the psychometric properties of this instrument have not been documented in different types of cancer diagnoses in the Mexican population.OBJECTIVE: To determine the psychometric properties of the HADS in a sample of patients with cancer from the Mexican population.METHOD: Four hundred patients from the National Cancer Institute participated, of which 226 were women (56.5%) and 174 men (43.6%), with a mean age of 47.4 ±14.1 years. Participants completed concurrently the HADS as well as the following inventories: 1. Beck Depression, 2. Beck Anxiety and 3. Distress Thermometer.RESULTS: A factor analysis adjusted to two factors explained 48.04% of the variance, with 12 items loading on these two factors in a way similar to the original version. The internal consistency of the overall scale was satisfactory (α=0.86). Cronbach's alphas for each subscale were .79 and .80. The concurrent validity assessed by way of correlations with concurrent measures showed significant associations (Pearson r=51-71, p<0.05).DISCUSSION AND CONCLUSION: The HADS has adequate construct validity, internal consistency and concurrent validity for its use in cancer patients from the Mexican population. The relevance of these results is a cost effective tool to provide timely mental health care early in oncological treatment for those in need. Detecting anxiety and depression symptoms through the HADS may benefit cancer patients by ensuring appropriate care that may increase their quality of life and treatment adherence, and reduce their hospital stays.

Identification of a metabolic and canonical biomarker signature in Mexican HR+/HER2-, triple positive and triple-negative breast cancer patients.

Infiltrating ductal breast cancer (IDC) is the principal tumor associated-malignancy in Mexican women. In IDC, the development of intermittent hypoxia leads to an adaptive response coordinated by the transcriptional factor HIF-1α. In the present pilot, retrospective/cross-sectional study, the HIF-1α expression was analyzed in 102 tru-cut biopsies from female patients (51 ± 12 years) without previous clinical treatment and compared to 31 normal breast biopsies. The 102 IDC samples corresponded to 56% of HER2-/HR+; 8% of HER2+/HR-; 22% of triple positive (HER2+/HR+); and 14% of triple negative (TN, HER2-/HR-) subtypes. To assess HIF-1α functionality, proteomic and kinetic analysis of glycolytic as well as mitochondrial enzymes, were determined. Validation of HIF-1α as cancer biomarker was assessed by determining the contents of the commonly used biomarkers c-MYC, Ki67, and H- and K-RAS, as well as metastatic and autophagy proteins. Proteomic analysis revealed that HIF-1α, c-MYC, HER2 and COXIV contents were significantly increased in all IDC subtypes vs. normal tissue. The contents and activities of glycolytic proteins were similar between normal and IDC samples, except for HER2-/HR+ where a substantial increase of HKII was observed. Significant increase in 2OGDH and E-cadherin was detected for TN samples vs. other IDC subtypes and for normal samples. These results clearly indicated that HIF-1α + COXIV + c-MYC (+ HER2 for HER2+ subtype) may be useful to depict a breast cancer metabolic marker pattern for diagnosis, whereas the contents of HIF-1α + c-MYC + 2OGDH + E-cadherin may be an alternative useful and reliable signature for TN subtype cancer prognosis.

Oxidative phosphorylation as a target to arrest malignant neoplasias.

Since Warburg proposed in 1956 that cancer cells exhibit increased glycolysis due to mitochondrial damage, numerous researchers have assumed that glycolysis is the predominant ATP supplier for cancer cell energy-dependent processes. However, chemotherapeutic strategies using glycolytic inhibitors have been unsuccessful in arresting tumor proliferation indicating that the Warburg hypothesis may not be applicable to all existing neoplasias. This review analyzes recent information on mitochondrial metabolism in several malignant neoplasias emphasizing that, although tumor cells maintain a high glycolytic rate, the principal ATP production may derive from active oxidative phosphorylation. Thus, anti-mitochondrial drug therapy may be an adequate adjuvant strategy to arrest proliferation of oxidative phosphorylation-dependent neoplasias.

Multi-biomarker pattern for tumor identification and prognosis.

In last decades, the basic, clinical, and translational research efforts have been directed to the identification of standard biomarkers associated with the degree of malignancy. There is an increasingly public health concern for earlier detection of cancer development at stages in which successful treatments can be achieved. To meet this urgent clinical demand, early stage cancer biomarkers supported by reliable and robust experimental data that can be readily applicable in the clinical practice, are required. In the current standard protocols, when one or two of the canonical proliferating index biomarkers are analyzed, contradictory results are frequently reached leading to incorrect cancer diagnostic and unsuccessful therapies. Therefore, the identification of other cellular characteristics or signatures present in the tumor cells either alone or in combination with the well-established proliferation markers emerge as an alternative strategy in the improvement of cancer diagnosis and treatment. Because it is well known that several pathways and processes are altered in tumor cells, the concept of "single marker" in cancer results incorrect. Therefore, this review aims to analyze and discuss the proposal that the molecular profile of different genes or proteins in different altered tumor pathways must be established to provide a better global clinical pattern for cancer detection and prognosis.

Cetuximab concomitant with gemcitabine and radiotherapy in advanced squamous cell carcinomas of upper aerodigestive tract: a pilot study.

PURPOSE: To explore the response and toxicity of advanced non-metastatic squamous cell carcinomas of upper aerodigestive tract (SCC-UADT) to a combination of cetuximab concomitant with gemcitabine and radiotherapy. METHODS: We managed patients with concomitant treatment of cetuximab (400 mg/m(2) as uploading dose, then 250 mg/m(2), IV) concomitant with gemcitabine (50 mg/m(2)) weekly for seven courses, and radiotherapy in classical fractionation until completion of 70 Gy. Primary endpoints were complete response (CR) to treatment and toxicity. We evaluated patients for toxicity on a weekly basis; evaluation of response included physical examination, endoscopy, computed tomography (CT) scan and biopsy when indicated, and was performed 6 weeks after completion of radiotherapy. Additional evaluations were done every 3 months to document disease status. Between November 2004 and November 2005, 20 patients were included. RESULTS: CR was 82.4%, overall response was 100%. Neck disease reached CR in 61.5% and partial in 38.5% of patients. The main toxicities were nausea, lymphopenia, neutropenia and mucositis. Grade 3 and 4 side effects were presented in 70.6% of patients, but mucositis, and lymphopenia without clinical repercussions, occurred in 88.2% of patients. Gastrostomy was required in 11.8% of patients to maintain nutrition. Radioepithelitis developed in 76.5%, but only three of these (23.1%) were grade III. Median overall survival was 53 months (range 6-55 months) and median progression-free survival has not yet been reached at the time of evaluation. CONCLUSIONS: Although toxicity is important, this approach has interesting activity and deserves further investigation.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

Follicular neoplasms of the thyroid: importance of clinical and cytological correlation.

BACKGROUND: Thyroid cancer presents as nodules. Thyroid nodules are frequent, but only 5-30% are malignant. Fine needle aspiration biopsy (FNAB) is useful for initial evaluation; nevertheless, malignancy is uncertain when follicular neoplasm is reported. Some factors can be associated with malignancy. Therefore, we analyzed our follicular neoplasms in order to identify those factors associated with a higher risk of malignancy. METHODS: We analyzed the clinical files of consecutive patients with cytological diagnoses of follicular neoplasm. RESULTS: From 1,005 cases of thyroid nodules, 121 were follicular neoplasms according to cytology. Of these, 75 were surgically treated. Definitive report showed 45 benign (60%) and 30 malignant (40%) cases. Benign cases included 29 goiters, 11 follicular adenomas, and 5 cases of thyroiditis. Malignant cases were comprised of 12 papillary carcinomas, 4 follicular carcinomas, 3 papillary carcinomas-follicular variant, 1 lymphoma, 1 teratoma, 5 medullary carcinomas, 2 insular carcinomas, 1 anaplastic carcinoma and 1 metastatic breast carcinoma. Tumor size of benign lesions was 3.43 ± 2.04 cm, and 4.67 ± 2.78 (p = 0.049) for malignant lesions. Age was 46.95 ± 15.39 years for benign lesions and 48.67 ± 17.28 for malignant lesions (p = 0.66). Fifty percent of males showed malignancy vs. 37.7% of females (p < 0.005). CONCLUSIONS: Our results suggest that size and gender, but not age, are associated with cytological pattern. Ultrasonographic characteristics may be useful discriminating patients with a higher risk of malignancy. FNAB is a useful tool for initial evaluation of thyroid nodules, but clinical evaluation can enhance predictive value.

Treatment experiences of testicular cancer in Hispanic patients with Down's syndrome at the National Cancer Institute of Mexico.

We present 4 case studies of patients with Down's syndrome and testicular germ-cell cancer, treated with conventional methods at the National Cancer Institute of Mexico, with similar outcomes as patients without this syndrome. There are several reports of testicular cancer arising in patients with Down's syndrome worldwide, mainly from Caucasian populations. We discuss some theories about the association and the possible increase of incidence.

Exploring the role of novel agents in the treatment of renal cell carcinoma.

Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals >or=50 years of age, and until recently, few treatments options were available for metastatic disease. The 5-year median survival for these patients with metastatic renal cell carcinoma has been estimated at <10%. This review explores the data of the most relevant trials focusing on new approaches with novel agents, including sunitinib, sorafenib, bevacizumab, temsirolimus, as well as their combinations with traditional agents. We describe mechanisms of action, activity, and toxicity profile of those agents, as well as administration schedules that have been studied in clinical trials.

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: Therapeutic and pharmacoeconomic perspectives

Background. Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). Methods. Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and biovailability parameters were calculated. Results. Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 ñ 0.30 µg/mL, AUC was 12.87 ñ 2.02 µg/mL and half-life was 6.72 ñ 0.97 h. Conclusions. Considering that the pharmacokinetic aim is to maintain plasm concentrations between 0.5 and 1.0 µg/mL for several hours while avioding high concentrations, i.e., of 10 µg/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration