Circulating cell-free-DNA concentration is a good biomarker for diagnosis of colorectal cancer in Mexican patients.

Colorectal cancer (CRC) is the third most common cancer in the world. Overall survival is related to clinical stage: more advanced stages show lower survival rates; therefore, they need to be monitored regularly with new, less invasive and more specific biomarkers. The concentration and integrity index of circulating cell-free DNA (ccfDNA) have been proposed as potential diagnostic and prognostic biomarkers for CRC, however, inconsistent results are still observed in different reports. Here we analyze these potential CRC biomarkers in a Mexican population. In this study, 124 patients with sporadic CRC and 37 healthy individuals were examined as a reference group. The ccfDNA was isolated from plasma samples of all included subjects. The ccfDNA concentration was determined by fluorometry and the integrity index (ALU247/ALU115 ratio) by quantitative PCR amplification (qPCR) of ALU sequences. The results show that ccfDNA concentration was higher in CRC patients than in the reference group (P=0.001). The integrity index showed no significant differences between these groups (P=0.258), except for histological type (P=0.012). A higher ccfDNA concentration was also associated with patients younger than 50 years (P=0.030). The ccfDNA concentration showed significant discriminatory power (AUC: 0.854, C.I.: 0.78-0.92, P=0.001) between patients and the reference group and between tumor-node-metastasis (TNM) stages. In conclusion, ccfDNA concentration proves to be a good diagnostic biomarker for CRC patients, whereas the integrity index did not show diagnostic utility.

Proapoptotic CD95L levels in normal human serum and sera of breast cancer patients.

The CD95 pathway is a critical apoptotic pathway used by immune cells to avoid cancer development. CD95 ligand (CD95L) is found in several forms, as a cell membrane-associated form, a soluble metalloprotease-cleaved form, and a soluble but membrane-bound CD95L released on cell-derived exosomes. In this study, we used a cell-based assay to evaluate the activity of proapoptotic CD95L in sera from healthy individuals and breast cancer patients. We confirmed that our cell-based assay using Jurkat cells was sensitive to the presence of proapoptotic CD95L in serum, and apoptosis induction by mechanisms other than CD95 was discriminated using apoptosis-resistant Jurkat subclones. Our results indicated a proapoptotic potential of normal serum that involved CD95L. Sera from breast cancer patients exhibited significantly decreased apoptosis induction, due to increased CD95 receptor levels compared with healthy women. Apoptotic potential tended to decrease as the Breast Imaging Reporting and Data System grade increased, and we observed restoration of proapoptotic potential after tumor removal. The CD95L in serum responsible for apoptotic induction was associated with high-molecular-weight particles, perhaps with exosomes. The sera of healthy individuals generally contain a proapoptotic environment, and this property is mainly maintained by the presence of CD95L. Furthermore, measurement of CD95L-mediated apoptosis induction by sera could be a useful parameter to be evaluated during cancer development and therapeutic response.

NME1 and DCC variants are associated with susceptibility and tumor characteristics in Mexican patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks third in cancer incidence globally and is the second leading cause of cancer-related mortality. The nucleoside diphosphate kinase 1 (NME1) and netrin 1 receptor (DCC) genes have been associated with resistance against tumorigenesis and tumor metastasis. This study investigates the potential association between NME1 (rs34214448 G > T and rs2302254 C > T) and DCC (rs2229080 G > C and rs714 A > G) variants and susceptibility to colorectal cancer development. METHODS: Samples from 232 colorectal cancer patients and 232 healthy blood donors underwent analysis. Variants were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were assessed using odds ratios (OR), and the p values were adjusted with Bonferroni test. RESULTS: Individuals carrying the G/T and T/T genotypes for the NME1 rs34214448 variant exhibited a higher susceptibility for develop colorectal cancer (OR = 2.68, 95% CI: 1.76-4.09, P = 0.001 and OR = 2.47, 95% CI: 1.37-4.47, P = 0.001, respectively). These genotypes showed significant associations in patients over 50 years (OR = 2.87, 95% CI: 1.81-4.54, P = 0.001 and OR = 2.99, 95% CI: 1.54-5.79, P = 0.001 respectively) and with early Tumor-Nodule-Metastasis (TNM) stage (P = 0.001), and tumor location in the rectum (P = 0.001). Furthermore, the DCC rs2229080 variant revealed that carriers of the G/C genotype had an increased risk for develop colorectal cancer (OR = 2.00, 95% CI: 1.28-3.11, P = 0.002) and were associated with age over 50 years, sex, and advanced TNM stages (P = 0.001). CONCLUSIONS: These findings suggest that the NME1 rs34214448 and DCC rs2229080 variants play a significant role in colorectal cancer development.

Effect of receiving a customizable brochure on breast cancer patients' knowledge about their diagnosis and treatment: A randomized clinical trial.

BACKGROUND: Patients' lack of knowledge about their own disease may function as a barrier to shared decision-making and well-being. This study aimed to evaluate the impact of written educational materials on breast cancer patients. METHODS: This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision-making, perceived quality of information received, and illness uncertainty. Follow-up occurred at 7-21 and 30-51 days post-randomization. CLINICALTRIALS: gov identifier: NCT05798312. RESULTS: One hundred sixty-five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline-endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline-recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision-making (p = 0.042). CONCLUSIONS: Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics.

Alpha 1-antitrypsin: a novel tumor-associated antigen identified in patients with early-stage breast cancer.

Several studies have demonstrated that sera from patients with cancer contain antibodies that recognize a unique group of autologous antigens called tumor-associated antigens (TAA). In the current study, we employed an immunoproteomic approach, combining 2DE, Western blot, and MALDI-MS to identify TAA in the sera of patients diagnosed with infiltrating ductal or in situ carcinoma breast cancer. Sera obtained from 25 newly diagnosed patients with stage II breast cancer and 20 healthy volunteers was evaluated for the presence of novel TAA. Alpha 1-antitrypsin (A1AT) antibodies were detected in 24 of 25 patients with breast cancer (96%) and in 2 of 20 controls (10%). Sensitivity of detection of autoantibodies against A1AT in patients with breast cancer was 96%. Our preliminary results suggest that A1AT and autoantibodies against alpha 1 antitrypsin may be useful serum biomarkers for early-stage breast cancer screening and diagnosis.

[Quality of life in Mexican women with breast cancer at different stages and its association with sociodemographic characteristics, comorbidities and procedural factors at the Mexican Institute of Social Security]. / Calidad de vida en mujeres Mexicanas con cáncer de mama en diferentes etapas clínicas y su asociación con características socio-demográficas, estados co-mórbidos y características del proceso de atención en el Instituto Mexicano del Seguro Social.

INTRODUCTION: Quality of life is the most studied PRO (patient reported outcome) in cancer patients. With early diagnosis and better treatments in breast cancer, this entity has been transformed in a chronic disease with longer survival. The joint effects of diseases and treatment on quality of life are each day more important to consider in survival patients. OBJECTIVE: To evaluate quality of life, socioeconomic factors, co-morbidities, and the attendance process impact on quality of life in breast cancer women with different clinical stages attending at the Instituto Mexicano del Seguro Social using the EORCT QLQ-C30 RESULTS: The scores of EORTC QLQ-C30 (v3) were: Global health status / QoL: 73.47 (± 20.81), physical functioning 76.98 (± 20.85), role functioning 76.60 (± 27.57), emotional functioning 64.53 (± 26.81), cognitive functioning 74.47 (± 26.02), social functioning 84.96 (± 23.20), fatigue 31.94 (± 25.45), nausea and vomiting 19.49 (± 26.93), pain 28.95 (± 27.27), dyspnea 15.29 (± 24.62), insomnia 35.13 (± 32.10), appetite lost 18.04 (± 28.75), 18.04 (± 28.75), constipation 19.20 (± 32.11), diarrhea 12.9 (± 24.25), financial difficulties 40.57 (± 37.26). The scores with EORTC QLQ-BR23 were: body image 74.84 (± 31.69), sexual functioning 13.73 (± 22.55), sexual enjoyment 32.86 (± 36.17), future perspectives 51.69 (± 38.00), systemic therapy side effects 30.82 (± 20.71), breast symptoms 22.85 (± 23.49), arm symptoms 27.53 (± 24.75), upset by hair loss 43.80 (± 44.01). CONCLUSIONS: Clinical stage in breast cancer is associated with differences in the scores from fatigue, nausea and vomiting and financial difficulties according to the evolution of the disease and the physical detriment associated. Socio-demographic features were related role functioning, fatigue and pain in single women with higher scores.

[Evaluation of patient satisfaction with the quality of health care received within the EORTC IN-PATSAT32 trial by patients with breast and colorectal cancer, and non-Hodgkin lymphoma at different stages. Correlation with sociodemographic characteristics, comorbidities and other procedural variables at the Mexican Institute of Social Security]. / Análisis de la satisfacción con los cuidados en salud a través del cuestionario EORTC IN-PATSAT32 en pacientes con cáncer de mama, linfoma no Hodgkin y cáncer colo-rectal en diferentes etapas clínicas. Relación con las características socio-demográficas, estados co-mórbidos y variables del proceso de atención en el Instituto Mexicano del Seguro Social.

INTRODUCTION: In Mexico cancer is a public health burden. Nowadays the health care systems pay special attention to patient's perception and satisfaction of the health care received. Satisfaction with quality of health care has an impact in the adherence to the treatment. OBJECTIVE: To evaluate the satisfaction with the quality of health care received at the IMSS in a group of cancer patients [non Hodgkin lymphoma (NHL), breast and colorectal cancer]. Socio-demographic features, co-morbid diseases, and attendance processes impact on satisfaction are also evaluated. RESULTS: 476 cancer patients were studied: 314 with breast cancer, 92 with NHL and 70 with colorectal cancer. In women with breast cancer the mean score to nurses' interpersonal skills in non-classified disease group and clinical stage III group were: 73.64 ± 32.53, 90.00 ± 18.25 respectively (p=0.005), nurses' availability in non-classified and clinical stage III group were: 69.71 ± 30.25, 89.21 ± 19.00 respectively (p=0.003). In subjects with NHL the mean scores for doctors' technical skills in clinical stage I and III groups, were: 63.69 ± 37.78, 80.30 ± 18.46 respectively (p=0.017), doctors' information provision scores in subject in clinical stage I and IV were: 49.40 ± 40.75, 79.49 ± 24.63 respectively (p=0.043). In the group of colorectal cancer patients the mean of the score to exchange of information between clinical stage II and clinical stage III group were 50.00 ± 41.83, 84.21 ± 22.37 respectively (p=0.036). Were not observed association between attendance processes features and general satisfaction. CONCLUSIONS: In Mexico 50% of cancer patients are attended at the IMSS. The continued evaluation of the satisfaction with health care received by the health care service users is important to enhance attention's quality.

[Evaluation of health-related quality of life in patients with non-Hodgkin lymphoma and colorectal cancer at different stages, attending the Mexican Institute of Social Security]. / Evaluación de la calidad de vida en pacientes con linfoma no Hodgkin y cáncer colo-rectal en diferentes etapas clínicas atendidos en el Instituto Mexicano del Seguro Social.

INTRODUCTION: In Mexico during 2008, were reported 127,604 new cancer cases, 6,347 of them were colorectal cancer cases and 4,276 non-Hodgkin lymphoma (NHL) cases. OBJECTIVE: To evaluate health related quality of life in non-Hodgkin lymphoma and colorectal cancer cases in different clinical stages, attended in a High Specialty Medical facility at the Instituto Mexicano del Seguro Social, during a 13 month period. RESULTS: 162 patients were included, 56.8% (n=92) with NHL and 43.2% (n=70) with colorectal cancer. The scores obtained in the NHL group were: Global health status/QoL: 67.75 (± 27.55), physical functioning 69.64 (± 29.98), role functioning 71.38 (± 33.73), emotional functioning 69.7 (± 26.57), cognitive functioning 75.36 (± 28.01), social functioning 79.35 (± 29.38), fatigue 35.27 (± 28.27), nausea and vomiting 13.41 (± 21.85), pain 28.08 (± 30.25), dyspnea 19.20 (± 32.11), insomnia 30.80 (± 38.03), appetite lost 26.45 (± 36.16), constipation 19.20 (± 32.11), diarrhea 12.32 (± 26.48), financial difficulties 26.09 (± 35.57). In colorectal cancer patients the scores were: Global health status/QoL: 68.21 (± 24.46), physical functioning 67.38 (± 30.45), role functioning 65.48 (± 35.70), emotional functioning 66.43 (± 26.84), cognitive functioning 78.57 (± 26.49), social functioning 75.24 (± 31.05), fatigue 37.78 (± 31.62), nausea and vomiting 20.00 (± 28.32), pain 37.38 (± 34.45), dyspnea 11.90 (± 26.64), insomnia 28.09 (± 35.73), appetite lost 23.81 (± 36.40), constipation 19.05 (± 32.88), diarrhea 20.95 (± 31.17), financial difficulties 34.76 (± 38.67). CONCLUSIONS: With these basal results is important a follow-up with special attention to the treatment and attendance processes, in patients with this neoplasms and their impact on the quality of life.

Expression of NK Cell Surface Receptors in Breast Cancer Tissue as Predictors of Resistance to Antineoplastic Treatment.

BACKGROUND: Currently, one of the most used strategies for the treatment of newly diagnosed patients with breast cancer is neoadjuvant chemotherapy based on the application of taxanes and anthracyclines. However, despite the high number of patients who develop a complete pathological clinical response, resistance and relapse following this therapy continue to be a clinical challenge. As a component of the innate immune system, the cytotoxic function of Natural Killer (NK) cells plays an important role in the elimination of tumor cells. However, the role of NK cells in resistance to systemic therapy in breast cancer remains unclear. The present project aims to evaluate the gene expression profile of human NK cells in breast cancer tissue resistant to treatment with taxanes-anthracyclines. METHODS: Biopsies from tumor tissues were obtained from patients with breast cancer without prior treatment. Histopathological analysis and ex vivo exposure to antineoplastic chemotherapeutics were carried out. Alamar blue and lactate dehydrogenase release assays were performed for quantitative analysis of tumor viability. Gene expression profiles from tumor tissues without prior exposure to therapeutic drugs were analyzed by gene expression microarrays and verified by polymerase chain reaction. RESULTS: A significant decrease in gene expression of cell-surface receptors related to NK cells was observed in tumor samples resistant to antineoplastic treatment compared with those that were sensitive to treatment. CONCLUSION: A decrease in NK cell infiltration into tumor tissue might be a predictive marker for failure of chemotherapeutic treatment in breast cancer.

Peri-infusional adverse reactions to rituximab in patients with non-Hodgkin's lymphoma.

BACKGROUND AND AIMS: Rituximab is effective in the treatment of B-cell lymphoid malignances and some autoimmune diseases. Most patients receiving the first infusion of rituximab experience symptoms that decrease with subsequent infusions. It is assumed that the first dose of rituximab should be infused slowly during a 6-h period and during 4-h periods subsequently. The aim of the study was to evaluate the frequency and severity of adverse reactions to rituximab in patients with non-Hodgkin's lymphoma. METHODS: This was an intensive pharmacovigilance prospective, observational, open labeled, multicenter cohort study conducted in 12 hospitals. Adults requiring treatment with rituximab (375 mg/m(2) body surface area) alone or with chemotherapy were included. Adverse reactions were graded according to the National Cancer Institute scale, whereas causality was established using the Naranjo algorithm. Infusions were classified as fast (0-90 min) and slow (>91 min). Fast infusions were used to analyze the associated adverse reactions. RESULTS: We included 550 adult patients. Total infusion episodes were 1,749 and 52 adverse reactions were reported in 22 patients (4%). Thirty-one of 52 adverse reactions occurred during the first infusion. The risk of adverse reactions was lower with the fast infusions (10/52 adverse reactions [19.23%]). All adverse effects were mild. Twenty-three adverse effects were possibly related to rituximab. CONCLUSIONS: Rituximab can be infused at a fast rate without an increase in adverse reactions. Peri-infusional adverse reactions are similar to those described for other populations but the incidence rate is lower. Rituximab has a favorable safety profile in patients with non-Hodgkin's lymphoma.