Hasil untuk "Cytology"

Shiva Abolhasani, Armin Mahmoud salehi Khesht, Atefeh Khodakarami et al.

Abstract Background Chemoresistance is still a significant obstacle to cancer therapy. Overexpression of the splicing factor 3b subunit 1 (SF3B1) and neurogenic locus notch homolog protein 1 (NOTCH1) factors is typically found in chronic lymphocytic leukemia (CLL), leading to the development of chemotherapy resistance. Objective The current investigation aims to evaluate the chemosensitivity of CLL cells by blocking NOTCH1 and SF3B1 using chitosan lactate (CL) nanoparticles (NPs). Methods We used CL-NPs loaded with anti-NOTCH1 and -SF3B1 small interfering RNAs (siRNAs) in combination with paclitaxel (PTX) to suppress NOTCH1 and SF3B1 in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) isolated from CLL cases to assess the impact of this therapeutic strategy on leukemic cell chemosensitivity. Further, the competing endogenous RNA (ceRNA) network that regulates NOTCH1 and -SF3B1 was constructed and enriched. Results Our findings showed that CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs-PTX significantly suppressed NOTCH1 and SF3B1 expression in PBMCs and BMMCs isolated from CLL cases in comparison with the untreated samples, leading to increased leukemic cell sensitivity to PTX and decreased the proliferative capacity of leukemic cells. The enrichment analysis highlighted the fundamental pathways where the NOTCH1- and SF3B1-associated ceRNA network exerts its influence in the context of CLL. Conclusions This study implies the efficacy of combined therapy by CL-NPs loaded with anti-NOTCH1/-SF3B1 siRNAs and PTX as a novel therapeutic strategy for CLL, even though further studies are required to warrant the findings. Graphical abstract

Ekaterina Pavlova, Rosen Ivanov, Desislava Abadjieva et al.

Diabetes mellitus (DM) causes male infertility through the suppression of spermatogenesis and testosterone biosynthesis. The impact of DM on male reproduction has mainly been investigated in adulthood, therefore we aimed to study the developmental effects of DM, induced in early life, on testicular cell population and fertility. Neonatal (NDM) and prepubertal DM (PDM) were induced in immature rats by streptozotocin administration on day 1 or day 10, respectively. Germ (GCs) and somatic cells (Sertoli—SCs and Leydig cells—LCs) were counted in pubertal (25 day) and post-pubertal (45 day) rats in tandem with the measurement of serum testosterone levels and the protein expression of androgen receptor. Glucose levels were higher in PDM than in NDM. Incomplete spermatogenesis and reduced GC number were found in PDM but not in NDM. LC number, testosterone, and luteinizing hormone (LH) levels were differently altered by both types of DM with a pronounced negative impact of PDM. Protein expression of androgen receptor in SCs was altered only in PDM. Reduced sperm concentration and motility was found in both groups. Thus, our results provide new insights into different mechanisms of action of PDM and NDM on developing germ cells that involved disturbances in androgen production by Leydig cells and androgen action in Sertoli cells.

Caiting Yang, Fengyu Chu, Xiaoli Chen et al.

Abstract Glutamine: fructose-6-phosphate amidotransferase (GFAT), a conserved enzyme across prokaryotic and eukaryotic species, is the first and rate-limiting step in the hexosamine biosynthetic pathway (HBP), diverting 2–5% of fructose-6-phosphate derived from glucose toward the synthesis of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a key substrate for the glycosylation of proteins and lipids. While substantial progress has been made in elucidating the basic biochemical properties and regulatory mechanisms of GFAT, its functional impact on pathological processes remains incompletely understood. Emerging evidence implicates GFAT in a spectrum of human diseases, including cancer, diabetes, cardiovascular disorders, and neurodegenerative conditions such as Alzheimer’s disease. This review aims to provide a comprehensive synthesis of current insights into GFAT’s role in disease etiology, with the goal of informing future research and therapeutic strategies targeting this essential metabolic regulator.

Sanam Meraj, Phillip Phung, Kelvin Lau et al.

The hemoflagellate parasite <i>Trypanosoma rangeli</i> is transmitted by triatomine kissing bugs and may co-infect humans together with its Chagas disease-causing congener <i>T. cruzi</i>. Using real-time quantitative polymerase chain reaction (RT-qPCR) and antimicrobial assays, we studied (<i>i</i>) the temporal and spatial distribution of <i>T. rangeli</i> in common bed bugs, <i>Cimex lectularius</i>, following oral ingestion and hemocoelic injection of <i>T. rangeli,</i> and (<i>ii</i>) the immune responses of bed bugs induced by <i>T. rangeli</i> infections. Irrespective of infection mode, no live <i>T. rangeli</i> were present in the bed bugs’ hemolymph, salivary glands, or feces. On day 1 following infection, the bed bugs strongly upregulated the antimicrobial peptide CL-defensin. Following hemocoelic injection of <i>T. rangeli</i>, live parasites were absent in any bed bug tissues examined throughout the 10-day study period. The ingestion of <i>T. rangeli</i>-infected blood had no significant effect on bed bug survival. Our findings indicate that bed bugs disable the development of <i>T. rangeli</i> within their body, in stark contrast to triatomine kissing bugs, which allow the development and transmission of <i>T. rangeli</i>. Our findings help unravel the intricate relationships between bed bugs and trypanosomes, and they contribute to our understanding of vector biology.

Laura Francesca Pisani, Isabella Teani, Maurizio Vecchi et al.

Accumulating evidence suggests that Interleukin-33 (IL-33), a member of the IL-1 family, has crucial roles in tissue homeostasis and repair, type 2 immunity, inflammation, and viral infection. IL-33 is a novel contributing factor in tumorigenesis and plays a critical role in regulating angiogenesis and cancer progression in a variety of human cancers. The partially unraveled role of IL-33/ST2 signaling in gastrointestinal tract cancers is being investigated through the analysis of patients’ samples and by studies in murine and rat models. In this review, we discuss the basic biology and mechanisms of release of the IL-33 protein and its involvement in gastrointestinal cancer onset and progression.

Sora Q. Kim, Kee-Hong Kim

Extracellular vesicles (EVs) are a highly heterogeneous population of membranous particles that are secreted by almost all types of cells across different domains of life, including plants. In recent years, studies on plant-derived nanovesicles (PDNVs) showed that they could modulate metabolic reactions of the recipient cells, affecting (patho)physiology with health benefits in a trans-kingdom manner. In addition to its bioactivity, PDNV has advantages over conventional nanocarriers, making its application promising for therapeutics delivery. Here, we discuss the characteristics of PDNV and highlight up-to-date pre-clinical and clinical evidence, focusing on therapeutic application.

Beatriz E. Sarmiento, Santiago Callegari, Kemel A. Ghotme et al.

Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor’s molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.

Dechen Fu, Luke Pfannenstiel, Abeba Demelash et al.

Abstract Colorectal cancer (CRC) is one of the most common and deadliest forms of cancer. Myeloid Cell Leukemia 1 (MCL1), a pro-survival member of the Bcl-2 protein family is associated with chemo-resistance in CRC. The ability of MCL1 to inhibit apoptosis by binding to the BH3 domains of pro-apoptotic Bcl-2 family members is a well-studied means by which this protein confers resistance to multiple anti-cancer therapies. We found that specific DNA damaging chemotherapies promote nuclear MCL1 translocation in CRC models. In p53null CRC, this process is associated with resistance to chemotherapeutic agents, the mechanism of which is distinct from the classical mitochondrial protection. We previously reported that MCL1 has a noncanonical chemoresistance capability, which requires a novel loop domain that is distinct from the BH3-binding domain associated with anti-apoptotic function. Herein we disclose that upon treatment with specific DNA-damaging chemotherapy, this loop domain binds directly to alpha-enolase which in turn binds to calmodulin; we further show these protein−protein interactions are critical in MCL1’s nuclear import and chemoresistance. We additionally observed that in chemotherapy-treated p53−/− CRC models, MCL1 nuclear translocation confers sensitivity to Bcl-xL inhibitors, which has significant translational relevance given the co-expression of these proteins in CRC patient samples. Together these findings indicate that chemotherapy-induced MCL1 translocation represents a novel resistance mechanism in CRC, while also exposing an inherent and targetable Bcl-xL co-dependency in these cancers. The combination of chemotherapy and Bcl-xL inhibitors may thus represent a rational means of treating p53−/− CRC via exploitation of this unique MCL1-based chemoresistance mechanism.

Sara El-Sahli, Khang Hua, Andrew Sulaiman et al.

Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.

Emi Dika, Elisabetta Broseghini, Elisa Porcellini et al.

Abstract Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.

Wenhui Zhong, Heping Liu, Li Deng et al.

Abstract Hepatocellular carcinoma (HCC) is a common primary liver malignancy lacking effective molecularly-targeted therapies. HBO1 (lysine acetyltransferase 7/KAT7) is a member of MYST histone acetyltransferase family. Its expression and potential function in HCC are studied. We show that HBO1 mRNA and protein expression is elevated in human HCC tissues and HCC cells. HBO1 expression is however low in cancer-surrounding normal liver tissues and hepatocytes. In HepG2 and primary human HCC cells, shRNA-induced HBO1 silencing or CRISPR/Cas9-induced HBO1 knockout potently inhibited cell viability, proliferation, migration, and invasion, while provoking mitochondrial depolarization and apoptosis induction. Conversely, ectopic overexpression of HBO1 by a lentiviral construct augmented HCC cell proliferation, migration and invasion. In vivo, xenografts-bearing HBO1-KO HCC cells grew significantly slower than xenografts with control HCC cells in severe combined immunodeficient mice. These results suggest HBO1 overexpression is important for HCC cell progression.

Kai Xue, Ji-Chuan Wu, Xi-Ya Li et al.

Abstract Rituximab/chemotherapy relapsed and refractory B cell lymphoma patients have a poor overall prognosis, and it is urgent to develop novel drugs for improving the therapy outcomes. Here, we examined the therapeutic effects of chidamide, a new histone deacetylase (HDAC) inhibitor, on the cell and mouse models of rituximab/chemotherapy resistant B-cell lymphoma. In Raji-4RH/RL-4RH cells, the rituximab/chemotherapy resistant B-cell lymphoma cell lines (RRCL), chidamide treatment induced growth inhibition and G0/G1 cell cycle arrest. The primary B-cell lymphoma cells from Rituximab/chemotherapy relapsed patients were sensitive to chidamide. Interestingly, chidamide triggered the cell death with the activation of autophagy in RRCLs, likely due to the lack of the pro-apoptotic proteins. Based on the RNA-seq and chromatin immunoprecipitation (ChIP) analysis, we identified BTG1 and FOXO1 as chidamide target genes, which control the autophagy and the cell cycle, respectively. Moreover, the combination of chidamide with the chemotherapy drug cisplatin increased growth inhibition on the RRCL in a synergistic manner, and significantly reduced the tumor burden of a mouse lymphoma model established with engraftment of RRCL. Taken together, these results provide a theoretic and mechanistic basis for further evaluation of the chidamide-based treatment in rituximab/chemotherapy relapsed and refractory B-cell lymphoma patients.

Rui Wei, Si Liu, Shutian Zhang et al.

Tumors are surrounded by complex environmental components, including blood and lymph vessels, fibroblasts, endothelial cells, immune cells, cytokines, extracellular vesicles, and extracellular matrix. All the stromal components together with the tumor cells form the tumor microenvironment (TME). In addition, extracellular physical and chemical factors, including extracellular pH, hypoxia, elevated interstitial fluid pressure, and fibrosis, are closely associated with tumor progression, metastasis, immunosuppression, and drug resistance. Cellular and extracellular components in TME contribute to nearly all procedures of carcinogenesis. By summarizing the recent work in this field, we make a comprehensive review on the role of cellular and extracellular components in the process of carcinogenesis and their potential application in early diagnosis of cancer. We hope that a systematic review of the diverse aspects of TME will help both research scientists and clinicians in this field.

Vadim K. Khlestkin, Tatyana V. Erst, Irina V. Rozanova et al.

Background It is well-documented that (bio)chemical reaction capacity of raw potato starch depends on crystallinity, morphology and other chemical and physical properties of starch granules, and these properties are closely related to gene functions. Preparative yield, amylose/amylopectin content, and phosphorylation of potato tuber starch are starch-related traits studied at the genetic level. In this paper, we perform a genome-wide association study using a 22K SNP potato array to identify for the first time genomic regions associated with starch granule morphology and to increase number of known genome loci associated with potato starch yield. Methods A set of 90 potato (Solanum tuberosum L.) varieties from the ICG “GenAgro” collection (Novosibirsk, Russia) was harvested, 90 samples of raw tuber starch were obtained, and DNA samples were isolated from the skin of the tubers. Morphology of potato tuber starch granules was evaluated by optical microscopy and subsequent computer image analysis. A set of 15,214 scorable SNPs was used for the genome-wide analysis. In total, 53 SNPs were found to be significantly associated with potato starch morphology traits (aspect ratio, roundness, circularity, and the first bicomponent) and starch yield-related traits. Results A total of 53 novel SNPs was identified on potato chromosomes 1, 2, 4, 5, 6, 7, 9, 11 and 12; these SNPs are associated with tuber starch preparative yield and granule morphology. Eight SNPs are situated close to each other on the chromosome 1 and 19 SNPs—on the chromosome 2, forming two DNA regions—potential QTLs, regulating aspect ratio and roundness of the starch granules. Thirty-seven of 53 SNPs are located in protein-coding regions. There are indications that granule shape may depend on starch phosphorylation processes. The GWD gene, which is known to regulate starch phosphorylation—dephosphorylation, participates in the regulation of a number of morphological traits, rather than one specific trait. Some significant SNPs are associated with membrane and plastid proteins, as well as DNA transcription and binding regulators. Other SNPs are related to low-molecular-weight metabolite synthesis, and may be associated with flavonoid biosynthesis and circadian rhythm-related metabolic processes. The preparative yield of tuber starch is a polygenic trait that is associated with a number of SNPs from various regions and chromosomes in the potato genome.

Donna J. Palmer, Dustin L. Turner, Philip Ng

In this study, we developed a single helper-dependent adenovirus (HDAd) to deliver all of the components (donor DNA, CRISPR-associated protein 9 [Cas9], and guide RNA [gRNA]) needed to achieve high-efficiency gene targeting and homology-directed repair in transduced cells. We show that these “all-in-one” HDAds are up to 117-fold more efficient at gene targeting than donor HDAds that do not express CRISPR/Cas9 in human induced pluripotent stem cells (iPSCs). The vast majority (>90%) of targeted recombinants had only one allele targeted, and this was accompanied by high-frequency indel formation in the non-targeted allele at the site of Cas9 cleavage. These indels varied in size and nature, and included large deletions of ∼8 kb. The remaining minority of recombinants had both alleles targeted (so-called bi-allelic targeting). These all-in-one HDAds represent an important platform for accomplishing and expanding the utility of homology-directed repair, especially for difficult-to-transfect cells and for in vivo applications.

Yao He, Bo Zhang, Hao Dong et al.

Navid Sobhani, Alberto D’Angelo, Matteo Pittacolo et al.

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated.

V. V. Dekhar, A. G. Osipov, L. F. Makarova et al.

Aim. To study the prevalence of behavioral and psychosocial risk factors (RF) of cardiovascular disease (CVD) among students aged 18 - 24 years. Materials and methods. The study used a questionnaire of epidemiological study ESSAY-Russian, adapted for students. In 2014 and 2015, random sample of students were interviewed in high schools of Barnaul (596 persons). Prevalences of smoking, low physical activity, non-healthy diet, stress and depression among students ware investigated. Results. Prevalence of smoking among students was 12,4%. Young men were 2.4 times more likely to smoke than women (p <0.001) and smoked more cigarettes per day. 72.3% of the students used alcohol, 3.6% of men and 1.0% of women used alcohol excessively. The number of women walking during 60 to 90 minutes per day was 3 times more than among boys (7.5 and 2.6%, p <0.05). Amount of walking time decreased with age. Evaluation of nutrition showed that 74.8% of students consumed insufficient amount of fish, 53% do not eat enough of fruits and vegetables, 45% consumed excessive table salt and 22% - sugar. Subclinical anxiety/depression had 21.5/9.6% of respondents, clinical anxiety/depression experienced 13.8/2.2% respectively. During the last 30 days the girls, compared with boys more likely to experience very high levels of stress (24.5 and 13%, p <0.001) and 1.5 times more than in a state of subclinical anxiety/depression (24.5 and 15, 3%; 15.8 and 9.7%, respectively; p <0.05). Conclusions: The estimation of the prevalence of behavioral and psychosocial risk factors of CVD is the basis for regional preventive programs among students.

Karl Munger, Hildegard I. D. Mack

Autophagy is an intracellular degradation pathway for long-lived proteins and organelles. This process is activated above basal levels upon cell intrinsic or environmental stress and dysregulation of autophagy has been linked to various human diseases, including those caused by viral infection. Many viruses have evolved strategies to directly interfere with autophagy, presumably to facilitate their replication or to escape immune detection. However, in some cases, modulation of autophagy appears to be a consequence of the virus disturbing the cell’s metabolic signaling networks. Here, we summarize recent advances in research at the interface of autophagy and viral infection, paying special attention to strategies that human tumor viruses have evolved.

Cláudio Kemp, Simone Elias, Karen Borrelli et al.

Objetivo: correlacionar os achados citológicos obtidos por punção com agulha fina dirigida pela ultra-sonografia de lesões não-palpáveis da mama, císticas ou sólidas, os aspectos ultra-sonográficos e os respectivos resultados histopatológicos das lesões que foram submetidas a cirurgia. Métodos: foram analisadas 617 lesões não-palpáveis visualizadas ao ultra-som. Realizou-se a punção aspirativa por agulha fina (PAAF) orientada pela ultra-sonografia, com análise citológica do material, diferenciando-as em cistos ou nódulos sólidos. Estes tiveram seu resultado citológico confrontado com o resultado histopatológico, nos casos em que foi realizada a biópsia cirúrgica. Resultados: das 617 lesões não-palpáveis, 471 eram cistos, sendo 451 cistos simples que apresentaram citologia negativa em todos os casos e 20 casos foram considerados cistos complexos. Destes, 3 (15%) tiveram resultado citológico positivo ou suspeito e em 2 casos confirmou-se malignidade. Dos 105 nódulos sólidos, 63 apresentaram citologia negativa, sendo 59 concordantes com a biópsia e houve 4 casos (0,3%) de resultado falso-negativo pela citologia. Todos, porém, apresentavam discordância entre imagem e citologia. Em 14 nódulos sólidos (13%), a citologia foi suspeita e, destes, 5 foram diagnosticados como carcinoma. Em outros 14 (13%), o material foi insatisfatório e 1 era carcinoma. Em 51 casos, o tríplice diagnóstico foi concordante e optou-se por seguimento clínico. Conclusão: a análise citológica do material dos cistos mamários simples é desnecessária, porém quando são complexos, a citologia é imperativa. Nas lesões sólidas não-palpáveis, é fundamental a correlação da citologia com o aspecto ultra-sonográfico e mamográfico; caso sejam discordantes, deve-se sempre prosseguir a investigação da lesão.<br>Purpose: to determine the relationship between fine needle aspiration cytology guided by ultrasound of nonpalpable breast lesions (cystic or solid masses) with the ultrasound and histopathological features of the biopsy lesions. Methods: a total of 617 nonpalpable lesions were analyzed by ultrasound. Fine needle aspiration cytology was guided by ultrasonography and the cysts were distinguished from the solid masses by comparing the biopsies. The cytologic results were compared with the histological results in the case surgical biopsy was carried out. Results: of the 617 nonpalpable lesions 471 were cysts (451 simple cysts with 100% negative cytology and 20 cases were considered complex cysts; 3 (15%) of these had a positive or suspected cytology and in 2 cases malignancy was confirmed. There were 105 solid masses, 63 of them with negative cytology. Fifty-nine cases had a negative biopsy, and 4 cases (0.3%) were false-negative but all of them presented disagreement between the cytological and image features; in 14 cases (13%) there was a suspected cytology and in 5 of them carcinoma was confirmed; in 14 cases (13%), the samples were insufficient, 1 case was carcinoma and in 51 cases, a triple diagnosis was concordant and the lesions were followed-up. Conclusion: cytological analysis of simple cysts is not required, but when they are complex, cytological analysis is mandatery. In the case of nonpalpable solid masses, cytology must be correlated with ultrasound and mammography features. If the results are discordant, the lesion should be followed-up.