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.

Selection of a GPER1 Ligand via Ligand-based Virtual Screening Coupled to Molecular Dynamics Simulations and Its Anti-proliferative Effects on Breast Cancer Cells.

BACKGROUND: Recent reports have demonstrated the role of the G Protein-Coupled Estrogen Receptor 1 (GPER1) on the proliferation of breast cancer. The coupling of GPER1 to estrogen triggers cellular signaling pathways related to cell proliferation. OBJECTIVE: Develop new therapeutic strategies against breast cancer. METHOD: We performed in silico studies to explore the binding mechanism of a set of G15 /G1 analogue compounds. We included a carboxyl group instead of the acetyl group from G1 to form amides with several moieties to increase affinity on GPER1. The designed ligands were submitted to ligand-based and structure-based virtual screening to get insights into the binding mechanism of the best designed compound and phenol red on GPER1. RESULTS: According to the in silico studies, the best molecule was named G1-PABA ((3aS,4R,9bR)-4-(6- bromobenzo[d][1,3]dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-carboxylic acid). It was synthesized and assayed in vitro in breast cancer (MCF-7 and MDA-MB-231) and normal (MCF-10A) cell lines. Experimental studies showed that the target compound was able to decrease cell proliferation, IC50 values of 15.93 µM, 52.92 µM and 32.45 µM in the MCF-7, MDA-MB-231 and MCF-10A cell lines, respectively, after 72 h of treatment. The compound showed better IC50 values without phenol red, suggesting that phenol red interfere with the G1-PABA action at GPER1, as observed through in silico studies, which is present in MCF-7 cells according to PCR studies and explains the cell proliferation effects. CONCLUSION: Concentration-dependent inhibition of cell proliferation occurred with G1-PABA in the assayed cell lines and could be due to its action on GPER1.

Antitumor Effects of Systemic DNAse I and Proteases in an In Vivo Model.

Background Cell-free DNA circulates in cancer patients and induces in vivo cell transformation and cancer progression in susceptible cells. Based on this, we hypothesized that depletion of circulating DNA with DNAse I and a protease mix could have antitumor effects. Study design The study aimed to demonstrate that DNAse I and a protease mix can degrade in vitro DNA and proteins from the serum of healthy individuals and cancer patients, and in vivo in serum of Wistar rats,. Moreover, the antitumor effect of the systemically administered enzyme mix treatmentwas evaluated in nude mice subcutaneously grafted with the human colon cancer cell line SW480. Results The serum DNA of cancer patients or healthy individuals was almost completely degraded in vitro by the enzymatic treatment, but no degradation was found with the enzymes given separately. The intravenous administration of the enzymes led to significant decreases in DNA and proteins from rat serum. No antitumor effect was observed in immunodeficient mice treated with the enzymes given separately. In contrast, the animals that received both enzymes exhibited a marked growth inhibition of tumors, 40% of them having pathological complete response. Conclusion This study demonstrated that systemic treatment with DNAse I and a protease mix in rats decreases DNA and proteins from serum and that this treatment has antitumor effects. Our results support the hypothesis that circulating DNA could have a role in tumor progression, which can be offset by depleting it. Further studies are needed to prove this concept.

Follow-up consultations for cervical cancer patients in a Mexican cancer center. Comparison with NCCN guidelines.

PURPOSE: This study aimed to determine the patterns of follow-up visits for cervix cancer in a national cancer center in Mexico. MATERIALS AND METHODS: The National Cancer Institute of Mexico is cancer center with 119 beds that mostly cares for an underserved and socially disadvantaged population. The medical records of cases of cervical cancer that had at least one year of clinical follow-up after being in complete response at the end of primary treatment were analyzed. We recorded the numbers of total and yearly follow-up visits and these were compared with the number of follow-up visits recommended by the National Comprehensive Cancer Network 2013, version 2 for cervical cancer. RESULTS: Between March and June 2007, the medical records of 96 consecutive patients were reviewed. Twenty (21%) of these met inclusion criteria and were selected. In the first year the median number of visits was 11 (4-20). In the ensuing years, 2nd, 3rd, 4th and 5th, the number of analyzed patients remaining in follow-up decreased to 17, 14, 13 and 9 respectively. There were 462 follow-up visits to primary treating services (Gynecology Oncology, Radiation Oncology and Medical Oncology) as compared to 220 suggested by the NCCN guidelines (X2 test p<0.0001). There were 150 additional visits to other services. CONCLUSIONS: Our results suggest that in our institution there is an overuse of oncological services by cervical cancer patients once treatment is completed.

The impact of DNA methylation technologies on drug toxicology.

INTRODUCTION: Drug toxicology is central to drug development. Despite improvements in our understanding of molecular and cell biology, high attrition rates in drug development continue, speaking to the difficulties of developing unequivocal methods to predict the efficacy and safety of drugs. AREAS COVERED: In this review, the authors provide a short overview of the 'omics' technologies that have been applied to drug toxicology, with an emphasis on a whole-genome DNA methylation analysis. Preliminary results from DNA methylation analysis technologies that may help in predicting response and efficacy of a drug are discussed. EXPERT OPINION: Currently, we cannot fully contextualize the application of epigenetics to the field of drug toxicology, as there are still many challenges to overcome before DNA methylation-based biomarkers can be effectively used in drug development. Comprehensive whole-genome DNA methylation methods for a unbiased analysis based on either microarray or next-generation sequencing need to be evaluated in drug toxicology in an intensive and systematic manner. Additionally, robust analysis systems need to be developed to decode the large amounts of data generated by whole-genome DNA methylation analyses as well as protocol standardization for reproducibility to develop meaningful databases that can be applied to drug toxicology.

A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care.

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

Emerging drugs for cervical cancer.

INTRODUCTION: There is a shortage of therapeutical agents for invasive cervical cancer in late stages of development; however, a number of promising molecules are currently in early phases of development. AREAS COVERED: This review briefly discusses the current achievements in treating cervical cancer with an emphasis in emerging agents based on a literature search on pubmed and related sites for cervical cancer information. This is not a systematic review. EXPERT OPINION: In advanced disease, modest survival gains have been achieved with cisplatin doublets. Contrariwise, chemoradiation has increased survival rates in locally advanced disease, but there is still room for improvement. Anti-vascular endothelial growth factor and anti-epidermal growth factor receptor monoclonal antibodies are promising molecules that are at present in late-phase development, but a high number of miscellaneous agents are in early development. Strong experimental bases support that the 'Achilles' heel' of cervical cancer are the HPV-E6/E7 oncogenes. Unfortunately, agents aimed at targeting these cervical cancer-driven players are found in very early development; hence, major research efforts must be focused on developing technological strategies for their effective targeting using nucleic acid-based vehicles for safe and effective delivery to cancer cells as well as accelerating the search for small-molecule inhibitors of E6/E7 themselves or their interacting cellular proteins.

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consistently failed in the clinical testing. There is however, a characteristic shared by these agents: -their high cost-. This is expected as drug discovery and development is generally carried out within the commercial rather than the academic realm. Given the extraordinarily high therapeutic drug discovery-associated costs and risks, it is highly unlikely that any single public-sector research group will see a novel chemical "probe" become a "drug". An alternative drug development strategy is the exploitation of established drugs that have already been approved for treatment of non-cancerous diseases and whose cancer target has already been discovered. This strategy is also denominated drug repositioning, drug repurposing, or indication switch. Although traditionally development of these drugs was unlikely to be pursued by Big Pharma due to their limited commercial value, biopharmaceutical companies attempting to increase productivity at present are pursuing drug repositioning. More and more companies are scanning the existing pharmacopoeia for repositioning candidates, and the number of repositioning success stories is increasing. Here we provide noteworthy examples of known drugs whose potential anticancer activities have been highlighted, to encourage further research on these known drugs as a means to foster their translation into clinical trials utilizing the more limited public-sector resources. If these drug types eventually result in being effective, it follows that they could be much more affordable for patients with cancer; therefore, their contribution in terms of reducing cancer mortality at the global level would be greater.

Anemia in cervical cancer patients: implications for iron supplementation therapy.

Iron deficiency and tumor bleeding are common causes of anemia in cervical cancer. Anemia has a negative prognostic influence, and its correction is thought to improve prognosis; therefore, most patients are treated with either transfusion and/or erythropoietin. At present little is known about the value of iron stores replenishment to increase hemoglobin levels in this setting. Untreated cervical cancer patients with a hemoglobin <12 g/dL were randomized to intramuscular iron or to transfusion. Iron dose was calculated according to [weight (kg)x(15--actual Hb)x2.4]+500 and administered by injections of 200 mg daily. In both arms, patients who did not achieve at least 10 g/dL hemoglobin before or during chemoradiation were transfused. Patients received standard pelvic radiation plus six weekly doses of cisplatin. Hematic counts were performed before starting chemoradiation and weekly thereafter. Fifteen patients were studied; six were assigned to iron and nine to transfusion. Mean basal hemoglobin levels were 9.9 and 9.5 g/dL respectively. Total iron, saturation index, binding capacity, and ferritin were within normal limits, although there was a high variability among the patients. The mean total dose of iron administered was 1229 mg. Two weeks after randomization, hemoglobin increased to 10.9 and 10.2 g/dL respectively. At wk 1 of treatment and thereafter, levels were higher in the iron arm, in whom the values were close or higher than 12 g/dL (p=0.03). The median number of units transfused were 0 in the iron group and 2 in the transfusion (p=0.02) arm. Parenteral iron seems to be effective to increase hemoglobin in cervical cancer patients.

Leucemia linfoblástica aguda del adulto: experiencia del Instituto Nacional de Cancerología de 1983-1987 / Adult acute lymphoblastic leukemia: experience at the Instituto Nacional de cancerología, 1983 - 1987

De enero 1983 a diciembre de 1987 se diagnosticaron en el INCan, 40 casos nuevos de leucemia linfoblástica aguda. Correspondieron a 20 hombres y 20 mujeres con edad media de 20.5 años (extremos 13-41 años). Seis pacientes se excluyeron del análisis, tres pacientes fallecieron sin recibir tratamiento y tres murieron en las primeras 96 horas de la inducción. Veintiocho recibieron tratamiento de inducción con esquema HOP: doxorrubicina, vincristina, prednisona y seis recibieron el esquema LSA2L2: ciclofosfamida, vincristina, adriamicina y prednisona, La profilaxis al SNC fue irregular. Se administró un tratamiento de mantenimiento convencional por dos ó tres años con pulsos mensuales de vincristina, prednisona, metotrexato semanal y 6-mercapturina diariamente. En los pacientes que recibieron LSA2L2, se intensificó con ciclos mensuales y alternos de Ara-C, ciclofosfamida y adriamicina. En 34 casos evaluables, 19 (56 por ciento) alcanzaron respuesta completa, seis (16.5 por ciento) respuesta parcial y nueve (26.5 por ciento) fallecieron durante la inducción. La respuesta completa en 9/19 pacientes, se alcanzó en las primeras cuatro semanas con una mediana de seguimiento de 319 días (141-1736+). Sólo dos pacientes continúan vivos en primera respuesta completa. Un paciente, falleció por causa no relacionada con la LLA y otro está perdido para seguimiento, ambos con respuesta completa. Se analizan las causas de muerte durante la inducción y el bajo porcentaje de sobrevivientes libres de enfermedad a largo plazo