Superficial acral fibromyxoma (SAF) is an uncommon benign dermal mesenchymal lesion of adults with predilection for acral sites, in particular the nail region. To date, less than 300 cases have been reported. SAFs consistently express CD34, but other diagnostic markers or specific genetic alterations have not been established yet. We describe 11 SAFs occurring in 7 men and 4 women aged 37 to 86years (median, 48 years). Mean size was 6mm (range, 4-20mm). Affected sites were fingers (n=5), toes (n=3), heel (n=1), calf (n=1), and unspecified digit (n=1). None of 10 patients with available follow-up (2-60months; median, 24months) developed recurrence. Histology showed relatively hypocellular vaguely lobulated nodules composed of bland-looking spindled or stellate fibroblast-like cells arranged into storiform or loose fascicles within a variably myxoid, fibromyxoid, or collagenous vascularized stroma. Immunohistochemistry showed expression of CD34 (9/10) and focal weak reactivity for epithelial membrane antigen (2/11). None of the lesions expressed protein S100 (0/11), MUC4 (0/11), or STAT6 (0/11). Loss of Rb1 immunoexpression was observed in 9 (90%) of 10 cases. All 7 cases with successful RB1 fluorescence in situ hybridization testing showed RB1 gene deletions, which was variably associated with co-loss of the corresponding 13q12 signal (monosomy at the 13q region). To our knowledge, this is the first study investigating the expression status of the tumor suppressor Rb1 in SAF by immunohistochemistry and fluorescence in situ hybridization. Our results showed frequent Rb1 deficiency as a possible driver molecular event in SAF (seen in 90% of cases) indicating relationship of SAF to the RB1-deleted tumor family.

• Klíčová slova
• Angiofibroma, Angiomyxoma, Deletion, Digital fibromyxoma, Rb1, Superficial acral fibromyxoma,
• MeSH
• biopsie MeSH
• delece genu * MeSH
• dospělí MeSH
• fenotyp MeSH
• fibrom chemie   diagnóza   genetika   patologie   chirurgie   MeSH
• genetická predispozice k nemoci MeSH
• hybridizace in situ fluorescenční * MeSH
• imunohistochemie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory kůže chemie   diagnóza   genetika   patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tumor burden MeSH
• ubikvitinligasy analýza   genetika   MeSH
• vazebné proteiny retinoblastomu analýza   genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nádorové biomarkery MeSH
• RB1 protein, human MeSH Prohlížeč
• ubikvitinligasy MeSH
• vazebné proteiny retinoblastomu MeSH

BACKGROUND: Mantle cell lymphoma (MCL) is a chronically relapsing malignancy with deregulated cell cycle progression. We analyzed efficacy, mode of action, and predictive markers of susceptibility to palbociclib, an approved CDK 4/6 inhibitor, and its combination with venetoclax, a BCL2 inhibitor. METHODS: A panel of nine MCL cell lines were used for in vitro experiments. Four patient derived xenografts (PDX) obtained from patients with chemotherapy and ibrutinib-refractory MCL were used for in vivo proof-of-concept studies. Changes of the mitochondrial membrane potential, energy-metabolic pathways, AKT activity, and pro-apoptotic priming of MCL cells were evaluated by JC-1 staining, Seahorse XF analyser, genetically encoded fluorescent AKT reporter, and BH3 profiling, respectively. MCL clones with gene knockout or transgenic (over)expression of CDKN2A, MYC, CDK4, and RB1 were used to estimate impact of these aberrations on sensitivity to palbociclib, and venetoclax. RESULTS: Co-targeting MCL cells with palbociclib and venetoclax induced cytotoxic synergy in vitro and in vivo. Molecular mechanisms responsible for the observed synthetic lethality comprised palbociclib-mediated downregulation of anti-apoptotic MCL1, increased levels of proapoptotic BIM bound on both BCL2, and BCL-XL and increased pro-apoptotic priming of MCL cells mediated by BCL2-independent mechanisms, predominantly palbociclib-triggered metabolic and mitochondrial stress. Loss of RB1 resulted in palbociclib resistance, while deletion of CDKN2A or overexpression of CDK4, and MYC genes did not change sensitivity to palbociclib. CONCLUSIONS: Our data strongly support investigation of the chemotherapy-free palbociclib and venetoclax combination as an innovative treatment strategy for post-ibrutinib MCL patients without RB1 deletion.

• Klíčová slova
• BCL2, Cyclin-dependent kinase (CDK) inhibitors, Mantle cell lymphoma (MCL), Palbociclib, RB1, Venetoclax,
• Publikační typ
• dopisy MeSH

The authors report a case of a 64-year-old man with chronic lymphocytic leukaemia (CLL) diagnosed 5 years ago. Recently, the patient was admitted with a tumour of the skin in the left lumbar region. Histological and immunohistochemical examinations established the diagnosis of Merkel cell carcinoma (MCC). Electron-microscopic examination revealed the formation of spherical aggregates of intermediate-sized filaments in the perinuclear region. The coincidence of MCC and CLl is rather rare and in published cases, no cytogenetic examinations were performed. We examined the RB1 gene using the interphase FISH method. A biallelic deletion in CLL tumour cells was detected; in MCC tumour cells, biallelic deletion was found in 33% of the cells and monoallelic deletion in 57% of the cells. In addition, chromosome 6 trisomy and 1p36 deletion were detected. Examination of non-neoplastic cells of the patient's skin showed a biallelic presence of the RB1 gene. According to the relevant literature, examination of the RB1 gene in CLL has informational value as a prognostic factor. The relationship between deletion of the RB1 gene and prognosis in MCC has not yet been determined and needs more research.

• MeSH
• chronická lymfatická leukemie genetika   MeSH
• delece genu * MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• Merkelův nádor genetika   patologie   MeSH
• mnohočetné primární nádory genetika   MeSH
• nádory kůže genetika   patologie   MeSH
• retinoblastomový protein genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• retinoblastomový protein MeSH

Branchioma (previously called ectopic hamartomatous thymoma, branchial anlage mixed tumor, or thymic anlage tumor) is a rare lower neck lesion with an adult male predominance and an uncertain histogenesis. Except for 4 cases, all branchiomas described in the literature were benign. Recently, HRAS mutation was detected in one case, but still little is known about the molecular genetic background of this rare entity. We herein report the histological, immunohistochemical, and molecular genetic analysis of a branchioma with a nested/organoid (neuroendocrine-like) morphology in a 78-year-old man. Histology revealed classical branchioma areas merging with nested/organoid cellular component lacking conventional features of malignancy. Immunohistochemistry was positive for high-molecular-weight cytokeratins. CD34 was expressed in the spindle cell component. Moreover, the tumor cells showed near-complete loss of retinoblastoma (RB1) expression (<1% of cells positive). All neuroendocrine markers (synaptophysin, chromogranin, and INSM1) were negative. Next-generation sequencing (TSO500 Panel) revealed 5 pathogenic/likely pathogenic mutations including 1 mutation in KRAS and 2 different mutations in each of MSH6 and PTEN. FISH and DNA sequencing were negative for RB1 gene alterations. To our knowledge, this is the first report of a branchioma showing misleading nested/organoid morphology and the first report on Rb1 immunodeficiency in this entity, in addition to multiple gene mutations revealed by NGS.

• Klíčová slova
• Androgen receptor, Branchioma, CD34, Ectopic hamartomatous thymoma, Head and neck, Neuroendocrine carcinoma-like, RB1 gene, Retinoblastoma,
• MeSH
• branchiom * patologie   MeSH
• lidé MeSH
• nádory brzlíku MeSH
• nádory glandulární a epitelové MeSH
• nádory měkkých tkání * MeSH
• nádory sítnice * MeSH
• organoidy patologie   MeSH
• represorové proteiny MeSH
• retinoblastom * genetika   patologie   MeSH
• senioři MeSH
• thymom MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• INSM1 protein, human MeSH Prohlížeč
• represorové proteiny MeSH

In our routine and consultative pathology practices, we have noticed that a relatively high proportion of spindle cell predominant trichodiscomas demonstrate a remarkable stromal admixture of adipose tissue, which along with spindle cells, prominent collagen bundles and myxoid change closely resembles spindle cell lipoma (SCL). To clarify their possible relationship to SCL, 25 cases of trichodiscoma and fibrofolliculoma with stromal "lipomatous metaplasia" were collected and examined using immunohistochemical stains [CD34 and retinoblastoma-1 (RB1) protein] and fluorescence in situ hybridization (RB1 deletion). The patients ranged in age from 35 to 81 years (median 64 years). The male to female ratio was almost equal (14:11). All tumors with a known location were situated on the face with a special predilection for the nose. All cases were sporadic, with all patients having a single lesion and showing no clinical features of Birt-Hogg-Dubé syndrome. No case with available follow-up presented with a recurrence or an otherwise aggressive clinical course. Spindle cell stroma was immunohistochemically positive for CD34 in 16 of 20 cases, and 18 of 19 cases showed loss of RB1 staining in lesional spindle cells. Fluorescence in situ hybridization analysis detected RB1 gene heterozygous deletion in 6 of 20 cases. We conclude that despite the SCL-like appearance of the investigated cases, the majority of them supposedly represent genuine spindle cell predominant trichodiscomas with adipose tissue admixture. However, there was a subset of histopathologically indistinguishable cases with proved RB1 deletion, which likely represent SCL with trichodiscoma/fibrofolliculoma-like epithelial/adnexal induction rather than spindle cell predominant variant of trichodiscoma.

• MeSH
• buňky stromatu patologie   MeSH
• databáze faktografické MeSH
• delece genu * MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• heterozygot MeSH
• hodnocení rizik MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• jehlová biopsie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipom genetika   patologie   MeSH
• nádory kůže genetika   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• vřetenobuněčný névus genetika   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

A novel endophytic fungus producing beta-glucosidase was isolated and characterized from pigeon pea (Cajanus cajan [L.] Millsp.), which has excellent properties in converting ginsenoside Rb1 to ginsenoside Rd in Panax notoginseng. According to the 16S rDNA gene sequence, the G11-7 strain was identified as Fusarium proliferatum, and the accession number KY303906 was confirmed in GenBank. The G11-7 immobilized spores, in which the activity of beta-glucosidase could reach 0.95 U/mL, were co-cultured with P. notoginseng plant material to obtain a continuous beta-glucosidase supply for the biotransformation of ginsenoside Rb1 to Rd. Under the liquid-solid ratio (20:1), initial pH (6.0), and temperature (30 °C) constituents, the maximum ginsenoside Rd yield was obtained as 9.15 ± 0.65 mg/g, which was 3.67-fold higher than that without fungal spore co-culture (2.49 ± 0.98 mg/g). Furthermore, immobilized G11-7 spores showed significant beta-glucosidase producing ability which could be recovered and reused for 6 cycles. Overall, these results suggested that immobilized G11-7 offered a promising and effective approach to enhance the production of ginsenoside Rd for possible nutraceutical and pharmaceutical uses.

• Klíčová slova
• Beta-glucosidase, Biotransformation, Fusarium proliferatum G11-7, Ginsenoside Rd, Immobilization,
• MeSH
• beta-glukosidasa metabolismus   MeSH
• biotransformace MeSH
• glykosidhydrolasy metabolismus   MeSH
• houby metabolismus   MeSH
• Panax notoginseng * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-glukosidasa MeSH
• ginsenoside Rb1 MeSH Prohlížeč
• ginsenoside Rd MeSH Prohlížeč
• glykosidhydrolasy MeSH

The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC.

• Klíčová slova
• CDK8, Colorectal cancer, E2F, H19, RB1, β-Catenin,
• MeSH
• analýza přežití MeSH
• beta-katenin metabolismus   MeSH
• cyklin-dependentní kinasa 8 genetika   metabolismus   MeSH
• databáze nukleových kyselin MeSH
• genové regulační sítě MeSH
• kolorektální nádory genetika   metabolismus   mortalita   patologie   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• prognóza MeSH
• regulace genové exprese u nádorů MeSH
• retinoblastomový protein metabolismus   MeSH
• RNA dlouhá nekódující genetika   MeSH
• RNA interference MeSH
• signální transdukce * MeSH
• stanovení celkové genové exprese MeSH
• transkripční faktory E2F metabolismus   MeSH
• transkriptom MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-katenin MeSH
• cyklin-dependentní kinasa 8 MeSH
• H19 long non-coding RNA MeSH Prohlížeč
• retinoblastomový protein MeSH
• RNA dlouhá nekódující MeSH
• transkripční faktory E2F MeSH

The nuclear arrangement of the ABL, c-MYC, and RB1 genes was quantitatively investigated in human undifferentiated HL-60 cells and in a terminally differentiated population of human granulocytes. The ABL gene was expressed in both cell types, the c-MYC gene was active in HL-60 cells and down-regulated in granulocytes, and expression of the RB1 gene was undetectable in HL-60 cells but up-regulated in granulocytes. The distances of these genes to the nuclear center (membrane), to the center of the corresponding chromosome territory, and to the nearest centromere were determined. During granulopoesis, the majority of selected genetic structures were repositioned closer to the nuclear periphery. The nuclear reposition of the genes studied did not correlate with the changes of their expression. In both cell types, the c-MYC and RB1 genes were located at the periphery of the chromosome territories regardless of their activity. The centromeres of chromosomes 8 and 13 were always positioned more centrally within the chromosome territory than the studied genes. Close spatial proximity of the c-MYC and RB1 genes with centromeric heterochromatin, forming the chromocenters, correlated with gene activity, although the nearest chromocenter of the silenced RB1 gene did not involve centromeric heterochromatin of chromosome 13 where the given gene is localized. In addition, the role of heterochromatin in gene silencing was studied in retinoblastoma cells. In these differentiated tumor cells, one copy of the RB1 gene was positioned near the heterochromatic chromosome X, and reduced RB1 gene activity was observed. In the experiments presented here, we provide evidence that the regulation of gene activity during important cellular processes such as differentiation or carcinogenesis may be realized through heterochromatin-mediated gene silencing.

• MeSH
• buněčná diferenciace MeSH
• buněčná membrána metabolismus   MeSH
• buněčné jádro chemie   metabolismus   MeSH
• G0 fáze MeSH
• G1 fáze MeSH
• geny abl genetika   MeSH
• heterochromatin metabolismus   ultrastruktura   MeSH
• HL-60 buňky MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• lidské chromozomy X MeSH
• lidské chromozomy, pár 13 MeSH
• lidské chromozomy, pár 8 MeSH
• metylace DNA MeSH
• nádorové buňky kultivované MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• protoonkogenní proteiny c-abl biosyntéza   MeSH
• protoonkogenní proteiny c-myc biosyntéza   genetika   MeSH
• retinoblastomový protein biosyntéza   genetika   MeSH
• translokace genetická MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• heterochromatin MeSH
• protoonkogenní proteiny c-abl MeSH
• protoonkogenní proteiny c-myc MeSH
• retinoblastomový protein MeSH

Spindle cell lipoma, cellular angiofibroma and mammary myofibroblastoma are mesenchymal tumours that have overlapping morphological and immunophenotypic features. Aberrations in chromosome 13q14 have been identified as a recurrent feature. We report a unique case of a 69-year-old woman who metachronously developed all three tumours. She developed a peri-urethral and a recurrent peri-vaginal cellular angiofibroma at age 54 and 57, respectively, a spindle cell lipoma at age 62 and a mammary myofibroblastoma at age 69. Dual-colour interphase fluorescent in situ hybridisation (FISH) revealed losses of RB1 and FOXO1 (13q14LOH [loss of heterozygosity]) within neoplastic cells. There was also loss of retinoblastoma (Rb) protein expression. To our knowledge, this is the first report of these three tumours arising in the same patient. The genetic link between these tumours supports the hypothesis that they may arise from the same progenitor cells. However, further research is required to elucidate the precise pathogenetic link.

• Klíčová slova
• Cellular angiofibroma, FISH, Fluorescence in situ hybridisation, Mammary myofibroblastoma, RB1, Spindle cell lipoma,
• MeSH
• angiofibrom genetika   patologie   MeSH
• fenotyp MeSH
• forkhead box protein O1 genetika   MeSH
• genetická predispozice k nemoci MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• lidské chromozomy, pár 14 * MeSH
• lipom genetika   patologie   MeSH
• nádorové biomarkery genetika   MeSH
• nádory močové trubice genetika   patologie   MeSH
• nádory prsu genetika   patologie   MeSH
• nádory vaginy genetika   patologie   MeSH
• nádory ze svalové tkáně genetika   patologie   MeSH
• sekundární malignity genetika   patologie   MeSH
• senioři MeSH
• ubikvitinligasy genetika   MeSH
• vazebné proteiny retinoblastomu genetika   MeSH
• ztráta heterozygozity * MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• forkhead box protein O1 MeSH
• FOXO1 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• RB1 protein, human MeSH Prohlížeč
• ubikvitinligasy MeSH
• vazebné proteiny retinoblastomu MeSH

In our routine and consultative pathology practices, we have repeatedly encountered an unusual subcutaneous fatty tumor with notable anisocytosis, single-cell fat necrosis, and patchy, often mild, adipocytic nuclear atypia. Because of the focal atypia, consultative cases have most often been received with concern for a diagnosis of atypical lipomatous tumor. Similar tumors have been described in small series under the designations "subcutaneous minimally atypical lipomatous tumors" and "anisometric cell lipoma." Sixty-six cases of this tumor type were collected and reviewed. Immunohistochemistry for p53, MDM2, CDK4, Retinoblastoma 1 (RB1) protein, CD34, S100, and CD163 was performed. Cases were tested for MDM2 gene amplification and RB1 gene deletion with fluorescence in situ hybridization (FISH) and for TP53 mutations by Sanger sequencing. Next-generation sequencing analysis using a panel of 271 cancer-related genes, including TP53, RB1, and MDM2, was also carried out. Our patient cohort included 57 male patients, 8 female patients, and 1 patient of unstated sex, who ranged in age from 22 to 87 years (mean: 51.2 y). All tumors were subcutaneous, with most examples occurring on the upper back, shoulders, or posterior neck (86.4%). Ten patients had multiple (2 to 5) lipomatous tumors, and the histology was confirmed to be similar in the different sites in 4 of them, including 1 patient who had a retinoblastoma diagnosed at age 1. The tumors were generally well circumscribed. At low magnification, there was notable adipocytic size variation with single-cell fat necrosis in the background associated with reactive histiocytes. Adipocytic nuclear atypia was typically patchy and characterized by chromatin coarsening, nuclear enlargement, and focal binucleation or multinucleation. Focal Lochkern change was frequent. In most instances, the degree of atypia was judged to be mild, but in 3 instances, it was more pronounced. Spindle cells were sparse or absent, and when present, cytologically bland. Thick ropy collagen bundles were absent. In all cases, p53 immunoexpression was noted (range: 2% to 20% of adipocytic nuclei), characteristically highlighting the most atypical cells. Twenty of 50 cases had MDM2 immunoreactivity, usually in <1% of the neoplastic cells, but in 4 cases, up to 10% of the cells were positive. Of 32 cases tested, 22 showed a near total loss of RB1 immunoexpression, and the remainder showed partial loss. Three of 13 cases showed RB1 gene deletion in >45% of the cells by FISH (our threshold value for reporting a positive result) with an additional 3 cases being very close to the required cutoff value. MDM2 gene amplification was absent in all 60 cases tested, including those with the greatest MDM2 immunoexpression and most pronounced atypia. All 5 tested cases showed no TP53 mutation with Sanger sequencing. Because of material quality issues, next-generation sequencing analysis could be performed in only 3 cases, and this did not reveal any recurrent mutations. All tumors were managed by simple local excision. Follow-up was available for 47 patients (range: 1 to 192 mo; mean: 27 mo) and revealed 2 local recurrences and no metastases. Dysplastic lipoma is a distinctive atypical fatty tumor variant that has p53 overexpression and RB1 gene abnormalities and lacks MDM2 gene amplification by FISH. These tumors have a strong male predominance and a notable tendency to involve the subcutaneous tissue of the shoulders, upper back and posterior neck. Multifocality is frequent (18.9% of patients with follow-up information), and there is a rare association with retinoblastoma. This tumor warrants separation from ordinary lipoma with fat necrosis, fat-rich spindle cell lipoma and the conventional form of atypical lipomatous tumor that features MDM2 gene amplification.

• MeSH
• amplifikace genu * MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• hybridizace in situ fluorescenční * MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• liposarkom * chemie   genetika   patologie   MeSH
• mladý dospělý MeSH
• mnohočetné primární nádory * chemie   genetika   patologie   MeSH
• mutace MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery * analýza   genetika   MeSH
• nádorový supresorový protein p53 * analýza   genetika   MeSH
• prediktivní hodnota testů MeSH
• protoonkogenní proteiny c-mdm2 genetika   MeSH
• retinoblastom * chemie   genetika   patologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tuková nekróza MeSH
• tukové buňky * chemie   patologie   MeSH
• ubikvitinligasy genetika   MeSH
• upregulace MeSH
• vazebné proteiny retinoblastomu genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• MDM2 protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• nádorový supresorový protein p53 * MeSH
• protoonkogenní proteiny c-mdm2 MeSH
• RB1 protein, human MeSH Prohlížeč
• TP53 protein, human MeSH Prohlížeč
• ubikvitinligasy MeSH
• vazebné proteiny retinoblastomu MeSH