SEOM-GEMCAD-TTD clinical guideline for the diagnosis and treatment of gastric cancer (2023).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, the incidence is lower and GC represents the tenth most frequent tumor and the seventh cause of cancer mortality. Molecular biology knowledge allowed to better profile patients for a personalized therapeutic approach. In the localized setting, the multidisciplinary team discussion is fundamental for planning the therapeutic approach. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors, and chemoradiation + surgery + adjuvant immunotherapy for the GEJ are current standards. For the metastatic setting, biomarker profiling including Her2, PD-L1, MSS status is needed. Chemotherapy in combination with checkpoint inhibitors had improved the outcomes for patients with PD-L1 expression. Her2 positive patients should receive antiHer2 therapy added to chemotherapy. We describe the different evidences and recommendations based on the literature.

The Barretos Cancer Hospital Animal Facility: Implementation and Results of a Dedicated Platform for Preclinical Oncology Models.

The Barretos Cancer Hospital Animal Facility (BCHAF) is a unique facility in Brazil exclusively dedicated to working with animal models for cancer research. In this article, we briefly present our modern facility and the main experiments performed, focusing on mutant strains of mice (PTCH-knockout and ApcMin mice), xenograft models, and patient-derived xenografts (PDXs). Our results show the progress and challenges in establishing these models and the need for having an appropriate representation of our cancer population to better understand tumor biology and to identify cancer biomarkers, which could be putatively targeted, allowing for personalized therapy.

The RAGE/multiligand axis: a new actor in tumor biology.

The receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein which actively participates in several chronic inflammation-related diseases. RAGE, in addition to AGEs, has a wide repertoire of ligands, including several damage-associated molecular pattern molecules or alarmins such as HMGB1 and members of the S100 family proteins. Over the last years, a large and compelling body of evidence has revealed the active participation of the RAGE axis in tumor biology based on its active involvement in several crucial mechanisms involved in tumor growth, immune evasion, dissemination, as well as by sculpturing of the tumor microenvironment as a tumor-supportive niche. In the present review, we will detail the consequences of the RAGE axis activation to fuel essential mechanisms to guarantee tumor growth and spreading.

Comparative Analysis of Systemic and Tumor Microenvironment Proteomes From Children With B-Cell Acute Lymphocytic Leukemia at Diagnosis and After Induction Treatment.

Among the childhood diseases, B-cell acute lymphocytic leukemia (B-ALL) is the most frequent type of cancer. Despite recent advances concerning disease treatment, cytotoxic chemotherapy remains the first line of treatment in several countries, and the modifications induced by such drugs in the organism are still poorly understood. In this context, the present study provided a comparative high-throughput proteomic analysis of the cumulative changes induced by chemotherapeutic drugs used in the induction phase of B-ALL treatment in both peripheral blood (PB) and bone marrow compartment (BM) samples. To reach this goal, PB and BM plasma samples were comparatively analyzed by using label-free proteomics at two endpoints: at diagnosis (D0) and the end of the cumulative induction phase treatment (D28). Proteomic data was available via ProteomeXchange with identifier PXD021584. The resulting differentially expressed proteins were explored by bioinformatics approaches aiming to identify the main gene ontology processes, pathways, and transcription factors altered by chemotherapy, as well as to understand B-ALL biology in each compartment at D0. At D0, PB was characterized as a pro-inflammatory environment, with the involvement of several downregulated coagulation proteins as KNG, plasmin, and plasminogen. D28 was characterized predominantly by immune response-related processes and the super expression of the transcription factor IRF3 and transthyretin. RUNX1 was pointed out as a common transcription factor found in both D0 and D28. We chose to validate the proteins transthyretin and interferon-gamma (IFN-γ) by commercial kits and expressed the results as PB/BM ratios. Transthyretin ratio was augmented after induction chemotherapy, while IFN-γ was reduced at the end of the treatment. Considering that most of these proteins were not yet described in B-ALL literature, these findings added to understanding disease biology at diagnosis and highlighted a possible role for transthyretin and IFN-γ as mechanisms related to disease resolution.

Current advances in the diagnosis and personalized treatment of breast cancer: lessons from tumor biology.

Breast cancer treatment has advanced enormously in the last decade. Most of this is due to advances reached in the knowledge regarding tumor biology, mainly in the field of diagnosis and treatment. This review brings information about how the genomics-based information contributed to advances in breast cancer diagnosis and prognosis perspective, as well as presents how tumor biology discoveries fostered the main therapeutic approaches available to treat such patients, based on a personalized point of view.

Loss of 5'-Methylthioadenosine Phosphorylase (MTAP) is Frequent in High-Grade Gliomas; Nevertheless, it is Not Associated with Higher Tumor Aggressiveness.

The 5'-methylthioadenosine phosphorylase (MTAP) gene is located in the chromosomal region 9p21. MTAP deletion is a frequent event in a wide variety of human cancers; however, its biological role in tumorigenesis remains unclear. The purpose of this study was to characterize the MTAP expression profile in a series of gliomas and to associate it with patients' clinicopathological features. Moreover, we sought to evaluate, through glioma gene-edited cell lines, the biological impact of MTAP in gliomas. MTAP expression was evaluated in 507 glioma patients by immunohistochemistry (IHC), and the expression levels were associated with patients' clinicopathological features. Furthermore, an in silico study was undertaken using genomic databases totalizing 350 samples. In glioma cell lines, MTAP was edited, and following MTAP overexpression and knockout (KO), a transcriptome analysis was performed by NanoString Pan-Cancer Pathways panel. Moreover, MTAP's role in glioma cell proliferation, migration, and invasion was evaluated. Homozygous deletion of 9p21 locus was associated with a reduction of MTAP mRNA expression in the TCGA (The Cancer Genome Atlas) - glioblastoma dataset (p < 0.01). In addition, the loss of MTAP expression was markedly high in high-grade gliomas (46.6% of cases) determined by IHC and Western blotting (40% of evaluated cell lines). Reduced MTAP expression was associated with a better prognostic in the adult glioblastoma dataset (p < 0.001). Nine genes associated with five pathways were differentially expressed in MTAP-knockout (KO) cells, with six upregulated and three downregulated in MTAP. Analysis of cell proliferation, migration, and invasion did not show any significant differences between MTAP gene-edited and control cells. Our results integrating data from patients as well as in silico and in vitro models provide evidence towards the lack of strong biological importance of MTAP in gliomas. Despite the frequent loss of MTAP, it seems not to have a clinical impact in survival and does not act as a canonic tumor suppressor gene in gliomas.

¿Tiene valor pedir más de un perfil inmunohistoquímico en tumores multicéntricos o multifocales de mama? / Has it any value to request more than one immunohistochemical profile in multicentric or multifocal breast tumors?

Introducción La estimación de la prevalencia de tumores mamarios multicéntricos y multifocales es muy variable según los distintos estudios analizados. Esto se debe, en gran parte, a la falta de consistencia al momento de definir ambas formas de presentación. Por este motivo, muchos autores hacen referencia a este tipo de tumor como carcinoma mamario múltiple. El tnm, uicc-ajcc (7ma edición) define a esta forma de presentación como múltiples lesiones de carcinoma mamario presentes en la misma mama de manera sincrónica. Según el Colegio Americano de Patólogos (cap), la caracterización biológica de la lesión de mayor tamaño tumoral es suficiente, salvo que se presenten discordancias entre los tipos histológicos o grados tumorales. A pesar de que la estrategia de evaluar una única lesión en este aspecto tiene claras ventajas en costos y viabilidad, el cáncer de mama es considerado en sí mismo una enfermedad heterogénea, y, al seguir las recomendaciones anteriormente expresadas, se estaría asumiendo que estos tipos de tumores múltiples tienen un comportamiento biológico homogéneo. Por tal motivo, en el presente estudio se analiza el comportamiento biológico (re, rp, her2 y Ki-67) en cada foco tumoral presente, para poder establecer si, al seguir las recomendaciones vigentes actualmente, no estaríamos subtratando a un grupo de nuestras pacientes. Objetivos Evaluar la concordancia en los perfiles inmunohistoquímicos de cada tumor presente de manera sincrónica en la mama. Establecer la asociación entre los tamaños, los tipos histológicos y el grado tumoral. Material y método Se realizó un estudio observacional, retrospectivo en pacientes con diagnóstico y confirmación por estudio histopatológico de pieza quirúrgica de carcinoma mamario multifocal o multicéntrico. De un total de 722 pacientes, se obtuvieron datos de 45 historias clínicas, en un período comprendido, entre marzo de 2015 y septiembre de 2016 (18 meses). Las pacientes analizadas fueron diagnosticadas y tratadas en la Unidad de Mastología de la Clínica Breast y el Hospital Italiano de la Ciudad de La Plata, Buenos Aires, Argentina. Los resultados histopatológicos e Inmunohistoquímicos (ihq) se obtuvieron de los patólogos pertenecientes a nuestro centro mastológico. El perfil ihq se realizó en tejido tumoral obtenido mediante biopsia con aguja gruesa o pieza quirúrgica. Se determinó: Receptores Hormonales para Estrógeno (re) y Progesterona (rp), her2 y Ki-67. Resultados • Se observó una incidencia de 6,23% de tumores multicéntricos, multifocales. • En cuanto al tipo histológico, la correlación entre biopsia con aguja gruesa y análisis de pieza quirúrgica fue del 100% (n:45 pacientes). • Grado histológico tumoral en los distintos focos: 84% (n=38) de concordancia y 16% (n=7) de discordancia. • Variabilidad de subtipos tumorales en cada foco: el 67% (n=30) no presentó discordancias. • Perfil inmunohistoquímico (ihq): el porcentaje de pacientes con concordancia en el perfil inmunohistoquímico y el subtipo tumoral fue superior al grupo de pacientes que presentaron discordancias. En el grupo de pacientes con discordancias, un 20% sobreexpresó el marcador her2. Conclusiones Teniendo en cuenta la heterogeneidad tanto intratumoral como entre los distintos focos que se presenta en estos tumores múltiples, es importante obtener la mayor información posible sobre la morfología y el perfil inmunohistoquímico.

Estimates of the prevalence of multicentric and multifocal breast tumors is highly variable depending on the different studies analyzed, and this is due largely to the lack of consistency when defining both forms of presentation. For this reason, many authors refer to this type of tumor as multiple breast carcinoma. The tnm (7th edition) defines this presentation as multiple lesions of breast carcinoma present in the same breast synchronously. According to the College of American Pathologists (cap), biological characterization of the lesion of the largest tumor is sufficient, unless discrepancies between the histological tumor types or degrees are presented. Although the strategy of evaluating a single lesion in this regard, has clear advantages in cost and viability, breast cancer is considered itself an heterogeneous disease, and following the recommendations previously expressed, it would be assuming that these type of multiple tumors have a homogeneous biological behavior. Therefore, in this study the biological behavior (er, pr, her2 and Ki-67) is analyzed in each tumor focus, to determine whether to follow the recommendations currently in force, we would not be sub-treatment a group of our patients.

Clinical behavior of solitary fibrous tumor: a retrospective review of 30 patients.

BACKGROUND: Solitary fibrous tumors (SFTs) are a rare type of soft tissue sarcoma of unpredictable clinical behavior. Some clinicopathologic characteristics have also been related to patient outcome. METHODS: This study is a retrospective review of 30 patients. We analyzed the clinical course and pathological factors to predict recurrence. RESULTS: The mean age was 55.9 years. Forty-five percent were located in the thoracic region. The mean tumor size was 10 cm (max24). Thirty-three percent had a relapse and 20 % have died. Median time to relapse was 7.18 (1-13) years. Median overall survival (OS) was 15.5 years (0-32). On histopathologic analysis, 6 % percent had >4 mitoses, 23 % had necroses, and 36 % had atypia/pleomorphism. Forty-three percent had tumor size >10 cm. Forty-six percent had at least one characteristic of malignancy. None of this data could predict clinical behavior by itself. CONCLUSIONS: SFT can be an aggressive disease and relapses can occur several years from diagnosis. We did not find any clinicopathologic factors that could predict the tumor behavior accurately. Nevertheless, it should be consider that we included different tumor locations and the sample size is small.

High expression of long non-coding RNA ATB indicates a poor prognosis and regulates cell proliferation and metastasis in non-small cell lung cancer.

BACKGROUND AND AIM: Long non-coding RNAs (lncRNAs) have been demonstrated to act as a critical regulator in the processes of tumor biology. In this study, whether lncRNA-ATB is a potential indicator for non-small cell lung cancer (NSCLC) was investigated and its biological function in NSCLC was also determined. METHODS: The expression levels of lncRNA-ATB in NSCLC tissues and cell lines were measured. A549 cell line was explored to investigate the functions of lncRNA-ATB in NSCLC. RESULTS: Real-time PCR results showed that lncRNA-ATB expression was up-regulated in both in NSCLC tissues and cell lines. High lncRNA-ATB expression in tumor tissue was associated with larger tumor size, lymph node metastasis, and distant metastasis in patients with NSCLC, respectively. In addition, the patients with high expression of lncRNA-ATB presented a lower survival probability. In vitro experiments showed that down-regulation of lncRNA-ATB promoted the cell apoptosis, whereas inhibited the cell viability, cell migration, and cell invasion. CONCLUSION: High expression of lncRNA-ATB indicated a poor prognosis and led to the cell proliferation and metastasis in NSCLC.

O-GlcNAcylation: The Sweet Side of the Cancer.

O-GlcNAcylation is an O-linked ß-N-acetylglucosamine (O-GlcNAc) moiety linked to the serine or threonine residues in proteins. O-GlcNAcylation is a dynamic post-translational modification involved in a wide range of biological processes and diseases such as cancer. This modification can increase and decrease the activity of enzymes as well as interfere with protein stability and interaction. The modulatory capacity of O-GlcNAcylation, as well as protein phosphorylation, is of paramount importance in the regulation of metabolism and intracellular signaling of tumor cells. Thus, understanding the regulation of O-GlcNAcylation in tumor cells and their difference compared to non-tumor cells may elucidate new mechanisms related to tumor generation and development, could provide a new marker to diagnosis and prognosis in patients with cancer and indicate a new target to cancer chemotherapy.

Retrospective study of melanocytic neoplasms in dogs and cats

Melanoma is one of the most lethal skin neoplasms among dogs and cats, and its incidence is increasing worldwide in the last years. The relation between the study of tumor biology and epidemiologic data from melanocytic tumors (melanomas and melanocytomas) can help in the achievement of an earlier and safer clinical diagnosis.However, epidemiologic data for these neoplasms are still rare in Brazil. Thus, we performed a retrospective study of melanocytic neoplasms in dogs and cats registered at the Animal Pathology Service of the School of Veterinary Medicine and Animal Science (SVMAS), University of São Paulo (USP), between January of 2000 and December of 2006. The epidemiological data extracted from pathology records regarded affected population (age, gender, hair color) and tumor characteristics (anatomic location and histological type). Of 2154 histopathological reports analyzed 193 (8.9%) were melanocytic neoplasms, of which 186 cases in dogs (96.4%) and only 7 in cats (3.6%). Male dogs, of

mixed breed, among 8 and 11 years of age and black hair were most affected by melanocytic neoplasms. Histological types most often found were epithelioid cell melanoma mainly located in the buccal cavity, and melanocytomas, located on the skin. Among cats, females between 8 and 11 years of age of mixed breed and black hair were most often affected. Epithelioid melanoma again presented as the most common histological type, located, however, on the skin. In conclusion, this casuistic demonstrated that melanocytic neoplasms develop mostly in middle age dogs with dark hair, in the oral cavity or skin, with histological type of epithelioid cells. Melanocytic tumors are rare in cats when compared to dogs; in our cases, they were diagnosed in middle aged female cats, mostly located in skin, and with epithelioid histological type. Epidemiological data strengthen the importance of early diagnosis of melanocytic tumors in Veterinary Medicine, promoting initiation of the most appropriate therapeutical process, improving diagnosis and promoting animal welfare.(AU)

Retrospective study of melanocytic neoplasms in dogs and cats

Melanoma is one of the most lethal skin neoplasms among dogs and cats, and its incidence is increasing worldwide in the last years. The relation between the study of tumor biology and epidemiologic data from melanocytic tumors (melanomas and melanocytomas) can help in the achievement of an earlier and safer clinical diagnosis.However, epidemiologic data for these neoplasms are still rare in Brazil. Thus, we performed a retrospective study of melanocytic neoplasms in dogs and cats registered at the Animal Pathology Service of the School of Veterinary Medicine and Animal Science (SVMAS), University of São Paulo (USP), between January of 2000 and December of 2006. The epidemiological data extracted from pathology records regarded affected population (age, gender, hair color) and tumor characteristics (anatomic location and histological type). Of 2154 histopathological reports analyzed 193 (8.9%) were melanocytic neoplasms, of which 186 cases in dogs (96.4%) and only 7 in cats (3.6%). Male dogs, of

mixed breed, among 8 and 11 years of age and black hair were most affected by melanocytic neoplasms. Histological types most often found were epithelioid cell melanoma mainly located in the buccal cavity, and melanocytomas, located on the skin. Among cats, females between 8 and 11 years of age of mixed breed and black hair were most often affected. Epithelioid melanoma again presented as the most common histological type, located, however, on the skin. In conclusion, this casuistic demonstrated that melanocytic neoplasms develop mostly in middle age dogs with dark hair, in the oral cavity or skin, with histological type of epithelioid cells. Melanocytic tumors are rare in cats when compared to dogs; in our cases, they were diagnosed in middle aged female cats, mostly located in skin, and with epithelioid histological type. Epidemiological data strengthen the importance of early diagnosis of melanocytic tumors in Veterinary Medicine, promoting initiation of the most appropriate therapeutical process, improving diagnosis and promoting animal welfare.

Oncogene-induced transcriptional patterns in established cell lines as a model for in vitro analysis of tumor biology

Established cell lines have long been used for in vitro studies of tumor biology, enabling investigators to control growth conditions and to draw important conclusions about the oncogenic microenvironment. However, gene expression behavior in cultured cells may not always reflect the actual in vivo scenario, and analysis derived from such experiments should take into consideration the existing differences between the two environments. We used suppression subtractive hybridization to study transcriptional changes elicited after oncogene transformation and cell line establishment. We found that transcriptional changes elicited in cultured cell lines are in fact representative of late events, and they do not occur early after oncogene transfection or activation. We also determined that a fraction of the transcriptional changes is oncogene specific, whereas other changes are shared between two or more different oncogenes.