• The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. (sciencedaily.com)
  • High levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors in multiple tumor types. (aacrjournals.org)
  • Together, these findings elucidate a prosurvival role for cyclin D3-CDK6 in metabolism, in addition to its role in cell-cycle progression, and suggest that high levels of cyclin D3 and CDK6 may predict response to CDK4/6 inhibitors. (aacrjournals.org)
  • Western blotting was performed to detect the protein levels of cyclin‑dependent kinase inhibitor P21 (P21), B‑cell lymphoma‑2 (Bcl‑2), matrix metalloproteinase 9 (MMP9) and E26 oncogene homolog 1 (ETS1). (spandidos-publications.com)
  • The precise regulation of the levels of cyclin proteins is fundamental to coordinate cell division with checkpoints, avoiding genome instability. (ox.ac.uk)
  • Cyclin D1 is a protein that in humans is encoded by the CCND1 gene. (wikipedia.org)
  • The CCND1 gene encodes the cyclin D1 protein. (wikipedia.org)
  • The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance throughout the cell cycle. (wikipedia.org)
  • Amplification of the CCND1 gene is present in: non-small cell lung cancers (30-46%) head and neck squamous cell carcinomas (30-50%) pancreatic carcinomas (25%) bladder cancer (15%) pituitary adenomas (49-54%) breast carcinoma (13%) Cyclin D1 overexpression is strongly correlated to ER+ breast cancer and deregulation of cyclin D1 is associated with hormone therapy resistance in breast cancer. (wikipedia.org)
  • Dr. Pestell and colleagues developed transgenic mice that could induce cyclin D1 expression in the breast and examined cells with cyclin D1 gene deleted. (sciencedaily.com)
  • Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis. (sciencedaily.com)
  • The identity of the higher molecular weight band (~ 45 kD) has not been determined, but may represent an alternative splice product of the cyclin C gene. (bdbiosciences.com)
  • The identity of this protein has not been determined, but may represent an alternative splice product of the cyclin C gene, as has been identified in other species. (bdbiosciences.com)
  • Cyclin C may play a dual role within the cell in its ability to regulate both cell cycle progression as well as gene transcription. (bdbiosciences.com)
  • Cyclin C associates with Cdk8, forming a complex which can induce gene transcription of Cdc2 (Cdk1). (bdbiosciences.com)
  • The IMPC applies a panel of phenotyping screens to characterise single-gene knockout mice by comparison to wild types. (mousephenotype.org)
  • The larger the gene name, the more frequently that gene is defective in that cancer type. (cancerquest.org)
  • HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)
  • At least eight mutations in the CDKN1B gene have been found to cause a relatively rare form of multiple endocrine neoplasia called type 4. (medlineplus.gov)
  • Most of the CDKN1B gene mutations that cause multiple endocrine neoplasia type 4 change single protein building blocks (amino acids) in the p27 protein. (medlineplus.gov)
  • Furthermore, exposure of cells to Cd resulted in a significant inhibition of expression of the cell cycle and growth regulating gene, cyclin D1. (cdc.gov)
  • Transfection of cells with SiRNA specifically targeting eIF4E gene expression also resulted in a significant inhibition of cyclin D1 gene expression suggesting that the observed inhibition of cyclin D1 gene in the Cd-treated cells is most likely mediated through inhibition of eIF4E gene. (cdc.gov)
  • Taken together, our results demonstrate that the exposure of cells to cadmium chloride resulted in cytotoxicity and cell death due to the enhanced ubiquitination and proteolysis and the consequent inhibition of eIF4E gene expression leading to diminished cellular level of critical genes such as cyclin D1. (cdc.gov)
  • MEN 4 is caused by an inactivating mutation of the CDKN1B gene, which codes for the cyclin dependent kinase inhibitor 1B protein, also known as p27 or p27KIP1. (msdmanuals.com)
  • Association between cyclin-dependent kinase inhibitor 2B antisense RNA 1 and zinc finger homeobox 3 gene polymorphisms and COVID-19 severity. (cdc.gov)
  • Cyclin D1 was originally cloned as a breakpoint rearrangement in parathyroid adenoma and was shown to be required for progression through the G1 phase of the cell cycle to induce cell migration, angiogenesis and to induce the Warburg effect. (wikipedia.org)
  • Cyclin D1 is a protein required for progression through the G1 phase of the cell cycle. (wikipedia.org)
  • Cyclin D1 overexpression has been shown to correlate with early cancer onset and tumor progression and it can lead to oncogenesis by increasing anchorage-independent growth and angiogenesis via VEGF production. (wikipedia.org)
  • The work supports the idea that cancer-causing proteins like cyclin D1 may drive cancer progression in part via miRNA biogenesis. (sciencedaily.com)
  • Collectively, our results reveal the molecular mechanism that controls the stability of D-type cyclins during cell-cycle progression, in development and in human cancer, and implicate AMBRA1 as a critical regulator of the RB pathway. (uniroma3.it)
  • Among the different cyclins controlling cell cycle progression, cyclin F does not partner with a CDK, but instead forms via its F-box domain an SCF (Skp1-Cul1-F-box)-type E3 ubiquitin ligase module. (ox.ac.uk)
  • It further inhibited cell-cycle progression in the G1 phase by four different mechanisms: rapid downregulation of cyclin D1, induction of Chk2 with simultaneous downregulation of Cdc25A, induction of the Cdk-inhibitor p21 Cip/Waf and inhibition of ribonucleotide reductase activity resulting in reduced dCTP and dTTP levels. (nature.com)
  • Because Cdc2 kinase is important for cell entry into mitosis, cyclin C's ability to regulate cell cycle progression may be attributed, in part, to modulation of Cdc2 protein expression.6 Cyclin C has a predicted molecular weight of 36 kD. (bdbiosciences.com)
  • β-TrCP- and Casein Kinase II-Mediated Degradation of Cyclin F Controls Timely Mitotic Progression. (ox.ac.uk)
  • Our results identify how cyclin A , cyclin B and Greatwall kinase coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phosphorylation . (bvsalud.org)
  • The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. (rcsb.org)
  • Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors. (nature.com)
  • Loss of AMBRA1 reduces sensitivity to CDK4/6 inhibitors by promoting the formation of complexes of D-type cyclins with CDK2. (uniroma3.it)
  • 2018) Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. (guidetopharmacology.org)
  • Thus, we assessed viability of cells lacking cyclin F upon challenging them with more than 180 different kinase inhibitors. (ox.ac.uk)
  • We find that SCF-cyclin F controls E2F1 ubiquitylation and degradation during the G2/M phase of the cell cycle and upon challenging cells with Chk1 inhibitors. (ox.ac.uk)
  • It promotes G0-G1 transition when phosphorylated by CDK3/cyclin-C. It also acts as a transcription repressor of E2F1 target genes. (nih.gov)
  • Cyclin D1-CDK4 inhibits pRb through phosphorylation, allowing E2F transcription factors to transcribe genes required for entry into the S phase. (wikipedia.org)
  • Cyclin D1 also binds to histone acetylases and histone deacetylases to regulate cell proliferation and cell differentiation genes in the early to mid-G1 phase. (wikipedia.org)
  • To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. (researchgate.net)
  • Forkhead box protein M1 (FOXM1) is a key transcription factor (TF) that regulates a common set of genes related to the cell cycle in various cell types. (mdpi.com)
  • Treatment with honey stops the tumour cells cycle by regulating some genes (cyclin D1, CDK2, p27Kip. (agenciasinc.es)
  • CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. (cancercentrum.se)
  • Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. (wikipedia.org)
  • Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4(AMBRA1) (also known as CRL4(DCAF3)) as the ubiquitin ligase that targets all three D-type cyclins for degradation. (uniroma3.it)
  • The degradation of cyclin F mediated by β-TrCP occurs at the G2/M transition. (ox.ac.uk)
  • Fisher, D. L. & Nurse, P. A single fission yeast mitotic cyclin B p34 cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins. (nature.com)
  • Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B. (bvsalud.org)
  • Two mitotic cyclin types, cyclin A and B, exist in higher eukaryotes , but their specialised functions in mitosis are incompletely understood. (bvsalud.org)
  • Cells lacking cyclin B can enter mitosis and phosphorylate most mitotic proteins , because of parallel PP2AB55 phosphatase inactivation by Greatwall kinase . (bvsalud.org)
  • Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. (nih.gov)
  • During development, loss of Ambra1 induces the accumulation of D-type cyclins and retinoblastoma (RB) hyperphosphorylation and hyperproliferation, and results in defects of the nervous system that are reduced by treating pregnant mice with the FDA-approved CDK4 and CDK6 (CDK4/6) inhibitor abemaciclib. (uniroma3.it)
  • Cyclin D1-CDK4 also enables the activation of cyclin E-CDK2 complex by sequestering Cip/Kip family CDK inhibitory proteins p21 and p27, allowing entry into the S phase. (wikipedia.org)
  • the majority of patients have dysregulated cyclin D expression. (bmj.com)
  • In this study, we evaluated cyclin D1, D2 and D3 protein expression in AL amyloidosis, and compared cyclin D positivity to other conventional laboratory parameters as a diagnostic tool and as a potential biomarker for minimal residual disease. (bmj.com)
  • The expression of Cyclin D1 mRNA was detected by qRT-PCR. (fluoridealert.org)
  • The expression of Cyclin D1 protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. (fluoridealert.org)
  • In the fluoride-exposed population, the results showed that with the increase in UF content, the expression of miR-4755-5p decreased gradually, while the mRNA transcription and protein expression of Cyclin D1 increased gradually. (fluoridealert.org)
  • The relative miR-4755-5p expression showed a negative correlation with Cyclin D1 expression. (fluoridealert.org)
  • Subsequently, in human osteoblasts treated with sodium fluoride (NaF), the results also showed that NaF caused low expression of miR-4755-5p and increased expression of Cyclin D1 . (fluoridealert.org)
  • Further, the results of miR-4755-5p mimic transfection confirmed that under the action of NaF, miR-4755-5p overexpression reduced Cyclin D1 protein expression within osteoblasts and further inhibited cell proliferation and activation. (fluoridealert.org)
  • The results demonstrate that fluoride exposure induced the downregulation of miR-4755-5p and downregulated miR-4755-5p promoted fluoride-induced osteoblast activation by increasing Cyclin D1 protein expression. (fluoridealert.org)
  • Cyclin D1 overexpression can also down-regulate Fas expression, leading to increased chemotherapeutic resistance and protection from apoptosis. (wikipedia.org)
  • In prior work, they showed that cyclin D1 regulates the non coding genome, and that the non-coding genome, in turn, regulates expression of cyclin D1. (sciencedaily.com)
  • They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. (sciencedaily.com)
  • Cyclin A expression above the median predicted an improved patient prognosis (HR = 0.71, 95%CI: 0.53 - 0.95). (ox.ac.uk)
  • CONCLUSION: This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer. (ox.ac.uk)
  • Like many cyclins, the expression of cyclin C oscillates throughout the cell cycle, with a peak observed during G1 phase. (bdbiosciences.com)
  • Moreover, in breast cancer cells, which express CDK4 instead of CDK6, palbociclib induced cell-cycle arrest instead of apoptosis, further indicating that expression of cyclin D3 and CDK6 in T-ALL cells promotes apoptosis in response to palbociclib. (aacrjournals.org)
  • Additionally, 16 of 18 nonleukemic cancer cell lines exhibiting high expression of cyclin D3 and CDK6 underwent apoptosis in response to palbociclib, and, in melanoma patient-derived xenografts, high cyclin D3 and CDK6 expression was associated with tumor regression after CDK4/6 inhibition. (aacrjournals.org)
  • Expression of cyclin D1, cyclin D2, and N-myc in embryos of the direct" by Kimberly Nath, Cara Fisher et al. (duq.edu)
  • Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation. (nih.gov)
  • This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. (wikipedia.org)
  • The cyclin D1-CDK4 complex promotes passage through the G1 phase by inhibiting the retinoblastoma protein (pRb). (wikipedia.org)
  • Cyclin D1-CDK4 also associates with several transcription factors and transcriptional co-regulators. (wikipedia.org)
  • Targets of the cyclin-dependent kinase Cdk1. (nature.com)
  • The final barrier to mitotic establishment corresponds to nuclear envelope breakdown, which requires a decisive shift in the balance of cyclin-dependent kinase Cdk1 and PP2AB55 activity. (bvsalud.org)
  • Magnetic Luminex Assay Kit for Cyclin D1 (CCND1) ,etc. (uscnk.com)
  • Genetic alterations of BCL2 (B-cell CLL/lymphoma 2), MYC [v-myc myelocytomatosis viral oncogene homolog (avian)] and CCND1 (cyclin D1) are the most frequently found alterations in human B-cell lymphomas. (haematologica.org)
  • Cancer hotspot mutations in D-type cyclins abrogate their binding to AMBRA1 and induce their stabilization. (uniroma3.it)
  • In addition to its role in regulating the cell cycle, cyclin D1 induces Dicer and thereby promotes the maturation of miRNA," says lead researcher Richard Pestell, M.D., Ph.D., Director of the Kimmel Cancer Center at Thomas Jefferson University and Chair of the Department of Cancer Biology. (sciencedaily.com)
  • However, in T-cell acute lymphoblastic leukemia (T-ALL), which predominately expresses CDK6 and the activating cyclin, cyclin D3, inhibition of CDK6 or cyclin D3 induces apoptosis. (aacrjournals.org)
  • MCF-7 cells, which have only one wild-type BRCA1 allele, were transfected with pcDNA3-beta-HA-hsBRCA1 plasmids via liposomes to reconstitute BRCA1 overexpression human breast cancer cell line, and tumoral xenografts with BRCA1 overexpression were subsequently established in BALB/c nude mice. (nih.gov)
  • Cyclin D1 overexpression is correlated with shorter cancer patient survival and increased metastasis. (wikipedia.org)
  • For mismatch repair deficiency and transforming growth factor β receptor type II (TGFBRII) overexpression there was a borderline association with a poorer prognosis (HR = 0.69, 95%CI: 0.46 - 1.04 and HR = 2.11, 95%CI: 1.02 - 4.40, respectively). (ox.ac.uk)
  • The screen revealed a striking synthetic lethality between Chk1 inhibition and cyclin F loss. (ox.ac.uk)
  • Chk1 inhibition in cells lacking cyclin F leads to DNA replication catastrophe. (ox.ac.uk)
  • Thus, Cyclin F restricts E2F1 activity during the cell cycle and upon checkpoint inhibition to prevent DNA replication stress. (ox.ac.uk)
  • Components of the canonical wingless (WNT) pathway, including WNT8b, WNT10a, WNT10b, frizzled 1 and 2 and TCF4 were upregulated at the messenger RNA and protein levels following Cyclin A2 depletion. (cnrs.fr)
  • Independent of CDK, cyclin D1 binds to nuclear receptors (including estrogen receptor α, thyroid hormone receptor, PPARγ and AR ) to regulate cell proliferation, growth, and differentiation. (wikipedia.org)
  • Silibinin dose-dependently decreased AOM-induced colonic cell proliferation, evidenced by proliferative cell nuclear antigen and cyclin D1 immunohistochemical staining, and induced apoptosis in these colon tissues, evidenced by terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling staining and cleaved poly(ADP-ribose) polymerase. (nih.gov)
  • The results, published in the Journal of Functional Foods, show that strawberry tree honey is capable of inhibiting the proliferation of tumour cells cultivated in laboratory plates - more specifically, those of a line of human colon adenocarcinoma (HCT-116) and another with metastatic characteristics (LoVo), widely used to investigate this type of tumour. (agenciasinc.es)
  • The polyclonal antiserum reacts with human and mouse cyclin C. A polypeptide fragment containing amino acids 290-303 (QGPNGSQNSSYSQS) at the C-terminus of human cyclin C, with the addition of a C-terminal cysteine (C) residue to facilitate conjugation to KLH, was used as immunogen. (bdbiosciences.com)
  • Furthermore, the group showed that many cancer patients encode a form of cyclin D1 that evades negative feedback from the non coding genome. (sciencedaily.com)
  • Luminal A subtype of breast cancer is the most common type and also has the best prognosis. (sciencedaily.com)
  • D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer(1), but the mechanisms that regulate their turnover are still being debated(2,3). (uniroma3.it)
  • Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C) , two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. (sdbonline.org)
  • Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor β receptor type II as prognostic factors for colorectal cancer: results of a 10-year prospective study using tissue microarray analysis. (ox.ac.uk)
  • The mechanisms underlying the prosurvival function of cyclin D3-CDK6 have not been elucidated, prompting Wang and colleagues to search for substrates that may promote cancer cell survival. (aacrjournals.org)
  • The metabolic function of cyclin D3-CDK6 kinase in cancer cell survival. (aacrjournals.org)
  • Different cancer types tend to depend on a limited number of 'driver' oncogene mutations. (cancerquest.org)
  • Selected oncogenes that have been associated with numerous cancer types are described in more detail below. (cancerquest.org)
  • It is one more piece of evidence that a healthy, balanced and natural diet can provide bioactive compounds with possible interesting effects on the control and development of diseases as critical as this type of cancer," concludes the researcher. (agenciasinc.es)
  • However, changes in regulation that reduce the amount or function of the p27 protein in the nucleus are found in many types of cancer. (medlineplus.gov)
  • One exception is hu- humanized SCID mice, the use of al oncogenic viruses that are strictly man T-cell lymphotropic virus type 1 surrogate hosts has not proven very species-specific, causing cancer in (HTLV-1): in addition to its ability to useful for defining tumour site con- humans only. (who.int)
  • While milestones have been surpassed throughout the decades for a number of cancer types, there are those that comprise of characteristics limiting effectiveness of treatments. (lu.se)
  • The tumour microenvironment (TME) contains several other cell types apart from cancer cells which play a role not only in the regulation of the environment but in response to treatments. (lu.se)
  • Donaldson, A. D. The yeast mitotic cyclin Clb2 cannot substitute for S phase cyclins in replication origin firing. (nature.com)
  • Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma. (wikipedia.org)
  • A- and B-type cyclins differentially modulate substrate specificity of cyclin-cdk complexes. (nature.com)
  • Miller, M. E. & Cross, F. R. Cyclin specificity: how many wheels do you need on a unicycle? (nature.com)
  • It is well established that statins display potent anticancer activity in several types of proliferating tumor cells. (nih.gov)
  • Cyclin D1 is expressed in all adult human tissues with the exception of cells derived from bone marrow stem cell lines (both lymphoid and myeloid). (wikipedia.org)
  • The researchers noticed that cells lacking cyclin D1 produced less of the miRNA-processing protein, Dicer, and therefore had reduced levels of mature miRNA. (sciencedaily.com)
  • The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes. (sciencedaily.com)
  • Here, we dissected the pathways that are responsible for EMT in cells deficient for Cyclin A2. (cnrs.fr)
  • In Cyclin A2-depleted normal murine mammary gland (NMuMG) cells expressing RasV12, we found that beta-catenin was liberated from the cell membrane and cell-cell junctions and underwent nuclear translocation and activation. (cnrs.fr)
  • Although various substrates of cyclin F have been identified, the vulnerabilities of cells lacking cyclin F are not known. (ox.ac.uk)
  • Replication catastrophe depends on accumulation of the transcription factor E2F1 in cyclin F-depleted cells. (ox.ac.uk)
  • Multiple endocrine neoplasia, type 4 (MEN 4) is an autosomal dominant syndrome characterized by adenomas and sometimes hyperplasia of the parathyroid glands and tumors of the pancreatic islet cells and/or pituitary gland. (msdmanuals.com)
  • however, the mechanisms underlying the regulation of cyclin F are poorly understood. (ox.ac.uk)
  • In the current study, the group sought to investigate the mechanism by which cyclin D1 regulates the biogenesis of non coding miRNA. (sciencedaily.com)
  • Using antisense RNA, Dr. Pestell's group was the first to show that cyclin D1 drives mammary tumor growth in vivo. (sciencedaily.com)
  • Bos taurus cyclin and CBS domain divalent metal cation transport mediator 2 (CNNM2), mRNA. (genscript.com)
  • ETS-1 and ETS-2 mRNA and protein levels were much higher in the ocular tissues of Tyrp-1-TAg mice than in control ocular tissues from wild-type mice. (molvis.org)
  • 6-phosphofructokinase (PFK1) and pyruvate kinase M2 (PKM2), enzymes that catalyze irreversible, rate-limiting steps in glycolysis, were directly phosphorylated and inhibited by cyclin D3-CDK6, suggesting that cyclin D3-CDK6 may have a unique role in glucose metabolism. (aacrjournals.org)
  • Based on a previous study, the aim of this study is to explore the role of miRNA in osteoblast activation of skeletal fluorosis via targeting of Cyclin D1 . (fluoridealert.org)
  • Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. (rcsb.org)
  • Like the mutations that cause multiple endocrine neoplasia type 4, these genetic changes reduce the amount of functional p27 available to control cell division. (medlineplus.gov)
  • Human Cyclin C polypeptide fragment aa. (bdbiosciences.com)
  • Cyclin C has been identified in both human and chicken species. (bdbiosciences.com)
  • The antibody should recognize human wild-type and mutant p53. (abcam.com)
  • p53 mutation and cyclin D1 amplification correlate with cisplatin sensitivity in xenografted human squamous cell carcinomas from head and neck. (lu.se)