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IMPORTANCE: Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1–selected tumors. OBJECTIVE: To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors. DESIGN, SETTING, AND PARTICIPANTS: The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022. INTERVENTIONS: Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity. MAIN OUTCOMES AND MEASURES: The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables. RESULTS: Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non–small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months). CONCLUSIONS AND RELEVANCE: In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy–naive metastatic NSCLC or EC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02794571

The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC).

Background: The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein that acts as a receptor of extracellular protein ligands of the epidermal growth factor (EGF/ErbB) family. It has been shown that EGFR is overexpressed by many tumours and correlates with poor prognosis. Therefore, EGFR can be considered as a very interesting therapeutic target for the treatment of a large variety of cancers such as lung, ovarian, endometrial, gastric, bladder and breast cancers, cervical adenocarcinoma, malignant melanoma and glioblastoma. Methods: We have followed a structure-based virtual screening (SBVS) procedure with a library composed of several commercial collections of chemicals (615,462 compounds in total) and the 3D structure of EGFR obtained from the Protein Data Bank (PDB code: 1M17). The docking results from this campaign were then ranked according to the theoretical binding affinity of these molecules to EGFR, and compared with the binding affinity of erlotinib, a well-known EGFR inhibitor. A total of 23 top-rated commercial compounds displaying potential binding affinities similar or even better than erlotinib were selected for experimental evaluation. In vitro assays in different cell lines were performed. A preliminary test was carried out with a simple and standard quick cell proliferation assay kit, and six compounds showed significant activity when compared to positive control. Then, viability and cell proliferation of these compounds were further tested using a protocol based on propidium iodide (PI) and flow cytometry in HCT116, Caco-2 and H358 cell lines. Results: The whole six compounds displayed good effects when compared with erlotinib at 30 μM. When reducing the concentration to 10μM, the activity of the 6 compounds depends on the cell line used: the six compounds showed inhibitory activity with HCT116, two compounds showed inhibition with Caco-2, and three compounds showed inhibitory effects with H358. At 2 μM, one compound showed inhibiting effects close to those from erlotinib. Conclusion: Therefore, these compounds could be considered as potential primary hits, acting as promising starting points to expand the therapeutic options against a wide range of cancers.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

To describe the echographic characteristics of optic disk melanocytoma using a high resolution 10–20MHz ophthalmic ultrasound.

Mediante una simulación de campaña de diagnóstico a gran escala para glaucoma primario de ángulo abierto, determinar su prevalencia en colaboradores mayores de 40 años de edad en la Universidad de Monterrey. Describir el perfil clínico epidemiológico que presentan los sujetos portadores de glaucoma y conocer los beneficios y las limitaciones del diagnóstico de glaucoma a gran escala.

El uso de un stent metálico autoexpandible como puente a la cirugía del cáncer de colon izquierdo en oclusión se ha señalado como tratamiento alternativo a la cirugía de urgencia. El objetivo del presente estudio fue comparar la morbimortalidad, el coste-beneficio y los resultados oncológicos a largo plazo de ambas opciones terapéuticas.

ABSTRACTIntroduction: Colorectal cancer is the third most common cancer worldwide. The prognosis of colorectal cancer patients still remains dismal and half of them will develop metastatic disease. Angiogenesis plays an essential role in colorectal tumorigenesis, and the VEGF pathway is one of the targets that has been validated up to now. The use of antiangiogenics along with chemotherapy has become an accepted standard for colorectal cancer.Areas covered: This review discusses the efficacy and safety profile of ramucirumab, a fully human immunoglobulin G1 monoclonal antibody against the vascular endothelial growth factor receptor-2 (VEGFR-2), for the treatment of second-line metastatic colorectal cancer upon progression to first-line chemotherapy including anti-angiogenics.Expert opinion: Ramucirumab in combination with chemotherapy represents a valid option in second-line treatment of advanced colorectal cancer patients, who progressed on previous bevacizumab-based combinations. This agent demonstrates a similar benefit in terms of overall survival to other angiogenesis inhibitors (bevacizumab and ziv-aflibercept) used in this setting.

La afectación microscópica de los márgenes de resección es un factor pronóstico fundamental en la cirugía del cáncer de páncreas. Sin embargo, su definición anatomopatológica no está estandarizada. Este estudio pretende identificar el porcentaje real de pacientes con resecciones R1 al analizar las piezas quirúrgicas con un protocolo estandarizado y evaluar sus implicaciones sobre la supervivencia.

RNA interference has emerged as a new and potent tool to knockdown the expression of target genes and to investigate their functions. For short time experiments with mammalian cell lines, RNA interference is typically induced by transfecting small interfering RNAs (siRNAs). Primary cells constitute important experimental systems in many studies because of their similarity to their in vivo counterparts; however, transfection of these cells has been found to be difficult. As a consequence, RNA interference of primary cells may result in mixed phenotypes because of the simultaneous presence in the same preparation of transfected and nontransfected cells. This may be particularly inconvenient when certain experiments (for example, biochemical analysis) should be performed.We use fluorescently labeled siRNAs to induce RNA interference in fibroblasts, and flow‐cytometry associated cell sorting to separate subpopulations of transfected cells according to fluorescence intensity.Flow cytometry allows one to discriminate between strongly‐ and weakly‐ or nonsilenced fibroblasts, since the fluorescence intensity of transfected cells is related to the number of internalized siRNA copies and to the mRNA knockdown efficiency.The use of fluorescently labeled siRNAs may allow one to isolate by flow‐cytometry associated cell sorting the most efficiently silenced primary cells for subsequent analysis. © 2007 International Society for Analytical Cytology

The combination of 5-fluorouracil (5-FU) plus leucovorin (LV) with oxaliplatin has become one of the standard treatments for advanced colorectal cancer (CRC). Two consecutive phase II trials assessed the efficacy and safety of combined therapy with oxaliplatin and high-dose 5-FU without LV for patients with advanced CRC. A total of 89 patients were enrolled in both trials. Fifty-nine patients in trial A underwent a scheduled regimen of biweekly oxaliplatin 85 mg/m2and weekly nonmodulated 5-FU 3.0 g/m2. Increased incidence of toxicity led to a 25% reduction in the starting dose of 5-FU (2.25 g/m2) for trial B. Patients treated in trial B showed a higher cumulative dose and relative dose intensity for oxaliplatin and 5-FU than those treated in trial A. Response to treatment, time to progression (TTP), overall survival (OS), and duration of response were evaluated as efficacy variables. Overall response rate was preserved despite the reduction in 5-FU dose (55.9% and 63.0%, respectively). Median durations of responses were 10.6 and 10.4 months, median TTPs were 7.7 and 7.3 months, and OS times were 21.7 and 13.1 months, respectively. Reduction in the starting 5-FU dose from 3.0 to 2.25 g/m2resulted in a decrease in the main grade 3/4 hematologic toxicities (neutropenia, 22.0% to 10.0%) and nonhematologic toxicities (diarrhea, 52.5% to 23.3%; nausea/vomiting, 18.6% to 3.3%). Neurosensory toxicity was similar in both trials (16.9% and 16.7%). Biweekly oxaliplatin in combination with nonmodulated high-dose 5-FU is an active, well-tolerated treatment that offers a lower cost than a modulated schedule for patients with advanced, metastatic CRC.

Abstract: Background: The continuous oral administration of UFT simulates protracted continuous intravenous infusion of fluorouracil, making this oral therapy a possible substitute for intravenous chemotherapy. Currently, 70% of cases of cancer will occur in patients over 65, and the feasibility of oral administration makes UFT a good drug for the elderly. The main objective of our trials was to evaluate the tolerance and benefits of this oral treatment in elderly patients with advanced colorectal cancer (CRC). Patients and methods: A total of 214 patients were included in two consecutive trials. Study number 1 included 106 patients treated with a continuous fixed dose of UFT 400 mg/24 hours plus oral folinic acid 45 mg/24 hours. Study number 2 included 108 patients treated with a continuous dose of UFT 400 mg/m2/24 hours without folinic acid. In both trials the main inclusion criterion was age >72 years. Patient characteristics of Study number 1 were: 46 females and 60 males, median age 74, median Karnofsky index 70, and liver metastasis 56%. Those of Study number 2 were: 42 females and 66 males, median age 76, median Karnofsky index 80, and liver metastasis 65%. Results: Study number 1: Ninety-six patients were evaluable for response and 98 for toxicity. The overall response rate (RR) was 18% (95% CI, 10–27%). Toxicity was mild with only one case of grade 3 thrombocytopenia, one case of grade 3 mucositis and 11 cases of grade 3–4 diarrhea. Overall median survival was 13.7 months. Study number 2: Ninety-two patients were evaluable for response and 108 for toxicity. The overall RR was 13% (95% CI, 6–20%). Toxicity was also mild without hematological toxicity and only nine cases of grade 3–4 diarrhea. Overall median survival was 11.8 months. Conclusion: UFT with or without modulation with folinic acid is an effective and comfortable treatment for elderly CRC patients.