PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “molecular profiling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed2026

Longitudinal Clinical, Physiological, and Molecular Profiling of Female Patients With Metastatic Cancer: Protocol and Feasibility of a Multicenter High-Definition Oncology Study.

PURPOSE: A substantial proportion of patients receiving genomically matched therapies do not achieve clinical benefit, underscoring the influence of nongenetic factors on cancer outcomes. High-Definition Oncology (HDO) proposes integrating longitudinal, multimodal patient data-spanning clinical, molecular, physiological, and behavioral domains-to enable truly individualized cancer care. This manuscript describes the HDO study design, framework, and feasibility results in women with metastatic cancer. METHODS: We initiated a prospective, multicenter observational study (HDO study; ClinicalTrials.gov identifier: NCT06590506) enrolling 300 female patients with newly diagnosed metastatic breast, lung, or colorectal cancer. Here, we report the study design, standardized workflows, prespecified feasibility criteria, and early internal pilot results. Eleven data modalities are collected longitudinally, including tumor and germline genomics, germline epigenomics, gut microbiome, blood and stool metabolomics and proteomics, exposome characterization, wearable-derived physiological monitoring, digital footprint assessment, medical imaging, and patient-reported outcomes. Standardized workflows govern clinical procedures, data acquisition, biospecimen processing, and quality control across all participating sites. RESULTS: Feasibility was evaluated in the first 30 participants (10% of planned accrual). Patients completed 100% of scheduled clinical visits, 97.4% of planned plasma collections, 80.7% of stool samples, and all tumor biopsies. Wearable devices captured activity, heart rate, sleep, and blood oxygen saturation data during 95.0%, 84.2%, 90.6%, and 70.7% of total patient-days, respectively. Biospecimens met predefined quality control metrics across all molecular modalities. Engagement with mobile applications for pain and emotion reporting exceeded 80%. CONCLUSION: The HDO study demonstrates the feasibility of comprehensive, longitudinal, multimodal data collection in women with metastatic cancer. This internal pilot establishes an integrated framework for future analyses aimed at characterizing disease trajectories, defining molecular and physiological determinants of outcomes, and developing patient-specific computational models.

Humans↗
PubMed2002

Molecular profiling of the role of the NF-kappaB family of transcription factors during alloimmunity.

Allograft rejection involves a complex network of multiple immune regulators and effector mechanisms. In the current study, we focused on the role of nuclear factor (NF)-kappaB/Rel. Previous studies had established that deficiency of the p50 NF-kappaB family member prolonged allograft survival only modestly. However, because of its crucial role in signal transduction in inflammatory and immune responses, we hypothesized that other NF-kappaB/Rel family members may produce more profound effects on alloimmunity. Therefore, in addition to p50, we analyzed the role of c-Rel, which is expressed predominantly in lymphocytes. Also, to investigate NF-kappaB activation in T cells, we examined transgenic mice that express a transdominant inhibitor of NF-kappaB [IkappaB(DeltaN)] regulated by a T cell-restricted promoter. Allograft survival was prolonged indefinitely in the c-Rel-deficient and IkappaB(DeltaN)-transgenic recipients. To determine the molecular basis of NF-kappaB modulation of rejection, we analyzed a panel of 58 parameters including effector molecules, chemokines, cytokines, receptors, and cellular markers using hierarchical clustering algorithms and self-organizing maps in p50(-/-), c-Rel(-/-), and IkappaB(DeltaN)-transgenic, experimental groups plus allogeneic-, syngeneic-, and lymphocyte-deficient (alymphoid) control groups. Surprisingly, profiles of gene expression in the c-Rel recipients (which have indefinite graft survival) were similar to the p50(-/-) and allogeneic recipients (which rapidly reject grafts). As expected, gene expression in the IkappaB(DeltaN) recipients (which also have indefinite graft survival) was similar to profiles of nonrejecting syngeneic and alymphoid recipients. Importantly, self-organizing maps identified a small subset of genes including several chemokine receptors and cytokines with expression profiles that correlate with graft survival. Thus, our results demonstrate a crucial role for NF-kappaB in acute allograft rejection, identify different molecular mechanisms of rejection by distinct NF-kappaB family members, and identify a small subset of inducible genes whose inhibition is linked to graft acceptance.

Algorithms↗
PubMed2026

Spindle Cell Predominant Anaplastic Pleomorphic Xanthoastrocytoma (WHO Grade 3) With Focal Piloid Features: A Rare Case Study With Comprehensive Molecular Profiling.

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor of the central nervous system. The typical form demonstrates relatively low-grade histologic features, whereas an anaplastic variant shows more aggressive behavior, including increased mitotic activity and necrotic changes. These tumors are often associated with alterations involving key growth signaling pathways and cell cycle regulatory genes, with molecular features that may resemble those seen in other high-grade astrocytic neoplasms. We describe an unusual example of an anaplastic pleomorphic xanthoastrocytoma showing focal piloid differentiation. The patient presented with acute neurologic symptoms, and imaging demonstrated a large, enhancing, well-circumscribed cerebral lesion with limited surrounding edema. Histologic evaluation revealed a highly cellular astrocytic neoplasm composed of spindle-shaped cells with marked pleomorphism, including scattered multinucleated forms, brisk mitotic activity, and necrotic areas. At the periphery, regions with elongated bipolar glial cells and occasional cytoplasmic inclusions suggestive of piloid morphology were identified. Molecular analysis demonstrated an activating alteration in the mitogen-activated protein kinase (MAPK) pathway along with additional genomic abnormalities, while mutations commonly associated with diffuse gliomas were not detected. The presence of piloid features within an otherwise anaplastic tumor is rare and may be relevant to the relatively favorable outcome observed during extended follow-up.

anaplastic↗
PubMed2006

Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors.

Malignant mesothelioma is an aggressive neoplastic proliferation derived from cells lining serosal membranes. The biological and clinical characteristics of epithelial type malignant mesothelioma are distinct from those of biphasic and sarcomatous type tumors. The goal of our study was to examine the molecular basis for this distinction. Microarray analysis confirmed that the molecular signatures of epithelial and biphasic histologic subtypes were distinct. Among the differentially expressed functional gene categories was the ubiquitin-proteasome pathway, which was upregulated in biphasic tumors. Cytotoxicity experiments indicated that 211H cells derived from biphasic tumors were synergistically sensitive to sequential combination regimens containing the proteasome inhibitor bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of epithelial tumor origin, was apoptosis. Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients.

Adult↗
PubMedDate not supplied

Molecular profile of the antrochoanal polyp: up-regulation of basic fibroblast growth factor and transforming growth factor beta in maxillary sinus mucosa.

BACKGROUND: Various pathogenetic mechanisms have been proposed to explain the development of antrochoanal polyps (ACPs); however, the cause is still largely unknown. The aim of this study was to characterize the expression and the potential role of a battery of molecular markers in the development of ACPs. A prospective controlled study of a case series was performed. METHODS: Tissue samples of maxillary sinus mucosa were obtained from 14 patients with ACPs, 17 patients with chronic nonpolypoid maxillary sinusitis, and 4 patients with normal maxillary sinus mucosa; RNAs were extracted from the sinus mucosa, and semiquantitative reverse transcription-polymerase chain reaction was performed for basic fibroblast growth factor, transforming growth factor P, and mucin genes (MUC), MUC5AC, MUC5B, and MUC8, to investigate their expression. RESULTS: The expression of basic fibroblast growth factor and transforming growth factor beta was significantly higher in ACPs than in chronic rhinosinusitis and healthy mucosa. Meanwhile, the levels of expression of MUC genes were higher in ACPs and chronic rhinosinusitis compared with healthy mucosa. CONCLUSION: These findings suggest that ACPs may represent an inflammatory reaction caused by overproduction of tissue-derived growth factors in an inductive environment.

Adult↗
PubMed2005

Profiling molecular targets of TGF-beta1 in prostate fibroblast-to-myofibroblast transdifferentiation.

The development of age-related proliferative disorders of the prostate gland is supported by transdifferentiation and cellular senescence processes in the stroma. Both processes are involved in remodeling of stromal tissue, as observed in benign prostatic hyperplasia (BPH), and in "reactive stroma" adjacent to prostate cancer (PCa). It has been assumed that TGF-beta1 plays a key role in the aging prostate by inducing premature senescence and favoring myofibroblast differentiation. Therefore, we evaluated the stromal cell phenotypes of human primary adult prostatic fibroblasts (n=3) and the molecular and cellular mechanisms of growth arrest after treatment with TGF-beta1 and of in vitro cellular senescence. Microarray analysis, quantitative PCR, immunofluorescence and western blot revealed that cellular senescence and transdifferentiation of fibroblasts have distinct underlying mechanisms, pathways and gene and protein expression profiles in human PrSCs. In clear contrast to senescent cells, TGF-beta1-treated cells morphologically transdifferentiated into myofibroblasts with dense cytoskeletal fibers and increased expression of smooth muscle cell alpha-actin, calponin and tenascin. TGF-beta1 induced neither expression of senescence-associated markers nor genes involved in terminal growth arrest, such as senescence-associated beta-galactosidase and cyclin-dependent kinase (cdk) inhibitors p16(Ink4A) and p21(Cip1) but increased p15(Ink4B) protein expression. Differentiation inhibitor (Id-1) protein level down-regulation was observed under both conditions. Genes specifically up-regulated by transdifferentiation but not by cellular senescence of PrSCs were metalloproteinase 1 tissue inhibitor (Timp1), transgelin (Tagln), gamma 2 actin (Actg2), plasminogen activator inhibitor 1 (Serpinel), insulin-like growth factor binding protein 3 (Igfbp3), parathyroid hormone-like hormone (Pthlp), Tgfb-1, four and a half LIM domains 2 (Fhl-2), hydrogen peroxide-inducible clone 5 (Hic5) and cartilage oligomeric matrix protein (Comp). Other genes, such as Cdc28 protein kinase 1 (Cks1b), v-myb myeloblastosis viral oncogene homolog (MybL2), pyruvate kinase, muscle 2 (Pkm2) and Forkhead box M1 (FoxM1), were down-regulated only upon TGF-beta1 treatment but not by cellular senescence. Pyruvate dehydrogenase kinase 3 (Pdk3) and connective tissue growth factor (Ctgf) were up-regulated and hyaluronan synthase 3 (Has3) down-regulated under both conditions. Moreover, GageC1, a prostate/testis-specific protein overexpressed in symptomatic BPH and PCa was induced in transdifferentiated stromal cells. Genes such as GageC1 could be promising targets for therapeutic inhibitors of stromal tissue remodeling and progression of BPH and PCa.

Cell Differentiation↗
PubMed2002

Molecular profiles of allograft rejection following inhibition of CD40 ligand costimulation differentiated by cluster analysis.

Recent technological advances in biomedical research, such as genome sequences and DNA microarrays, have dramatically increased the size of relevant databases. A major challenge is the extraction of a limited number of parameters from these databases that can differentiate and diagnose complex biological states. In a model of cardiac transplantation investigating immunosuppression by inhibition of CD40 ligand costimulation, we have applied a combination of cluster algorithms and self-organizing maps to analyze a panel of 60 candidate genes. Dendrograms generated by cluster analysis distinguished different molecular bases of rejection. Using self-organizing maps, we identified nine genes (CD4, CCR3, CCR5, LT beta, MIP-1 alpha, MIP-2, CD8 alpha, IP-10, and RANTES), each with a unique profile of transcriptional expression, that reproduce the differentiation of states of rejection in dendrograms. Using histology and immunohistochemistry, we correlated differential regulation of CD4 and CD8 at the levels of mRNA and protein. Our strategy of data reduction successfully decreased the number of genes to nine, which are sufficient to differentiate distinct states of rejection in our experimental protocol.

Animals↗
PubMed2004

Early regeneration genes: Building a molecular profile for shared expression in cornea-lens transdifferentiation and hindlimb regeneration in Xenopus laevis.

Recent studies in Xenopus laevis have begun to compare gene expression during regeneration with that of the original development of specific structures (e.g., the hindlimb and lens), while other studies have sought differences in gene expression between regeneration-competent and regeneration-incompetent stages. To determine whether there are any similarities between the regeneration of different structures, we have used a differential screen to seek shared early gene expression between hindlimb regeneration and cornea-lens transdifferentiation in the Xenopus tadpole. We have isolated 13 clones representing genes whose expression is up-regulated within the first few days of both regenerating processes and which are not demonstrably up-regulated in the context of basic wound healing. Furthermore, all of these genes also show prominent late embryonic expression. The expression patterns and putative identities of all 13 genes are presented, and a model is considered that allows us to characterize and profile important changes in gene expression, which might be shared among various regenerating and developmental systems.

Animals↗
PubMed2004

Molecular profiling of malignant peripheral nerve sheath tumors associated with neurofibromatosis type 1, based on large-scale real-time RT-PCR.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a complex range of clinical symptoms. The hallmark of NF1 is the onset of heterogeneous (dermal or plexiform) benign neurofibromas. Plexiform neurofibromas can give rise to malignant peripheral nerve sheath tumors (MPNSTs), and the underlying molecular mechanisms are largely unknown. RESULTS: To obtain further insight into the molecular pathogenesis of MPNSTs, we used real-time quantitative RT-PCR to quantify the mRNA expression of 489 selected genes in MPNSTs, in comparison with plexiform neurofibromas. The expression of 28 (5.7%) of the 489 genes was significantly different between MPNSTs and plexiform neurofibromas; 16 genes were upregulated and 12 were downregulated in MPNSTs. The altered genes were mainly involved in cell proliferation (MKI67, TOP2A, CCNE2), senescence (TERT, TERC), apoptosis (BIRC5/Survivin, TP73) and extracellular matrix remodeling (MMP13, MMP9, TIMP4, ITGB4). More interestingly, other genes were involved in the Ras signaling pathway (RASSF2, HMMR/RHAMM) and the Hedgehog-Gli signaling pathway (DHH, PTCH2). Several of the down-regulated genes were Schwann cell-specific (L1CAM, MPZ, S100B, SOX10, ERBB3) or mast cell-specific (CMA1, TPSB), pointing to a depletion and/or dedifferentiation of Schwann cells and mast cells during malignant transformation of plexiform neurofibromas. CONCLUSION: These data suggest that a limited number of signaling pathways, and particularly the Hedgehog-Gli signaling pathway, may be involved in malignant transformation of plexiform neurofibromas. Some of the relevant genes or their products warrant further investigation as potential therapeutic targets in NF1.

Adolescent↗
PubMed2002

[Tissue microarray technology--a new and powerful tool for the molecular profiling of tumors].

Tissue Microarrays (TMA) are the products of a new technology that offers rapid and simultaneous analysis of up to 1000 different archival samples. Sections from TMA blocks can be used for all different types of in situ tissue analysis including immunohistochemistry and in situ hybridization. The technology helps to implement the vast knowledge that was discovered by the human genome project and facilitates the molecular understanding of various benign and malignant processes. In this article we describe the process of TMA construction and review the main studies that applied the technology to characterizing tumors and precancerous lesions.

Biomarkers, Tumor↗
PubMed2004

Molecular profiles of neurofibromatosis type 1-associated plexiform neurofibromas: identification of a gene expression signature of poor prognosis.

PURPOSE: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a complex variety of clinical symptoms. The hallmark of NF1 is the development of heterogeneous benign neurofibromas, which may appear as dermal neurofibromas or plexiform neurofibromas. NF1 patients with plexiform neurofibromas are at risk of developing malignant peripheral nerve sheath tumors. EXPERIMENTAL DESIGN: To obtain additional insight into the molecular pathogenesis of plexiform neurofibromas, we used real-time quantitative reverse transcription-PCR assays to quantify the mRNA expression of 349 selected genes in plexiform neurofibromas in comparison with dermal neurofibromas and patient-matched malignant peripheral nerve sheath tumors. RESULTS: Thirty genes were significantly up-regulated in plexiform neurofibromas compared with dermal neurofibromas. None were down-regulated. The up-regulated genes mainly encoded transcription factors and growth factors and secreted proteins, cytokines, and their receptors, pointing to a role of paracrine and autocrine signaling defects in the genesis of plexiform neurofibromas. We also identified a gene expression profile, based on MMP9, FLT4/VEGFR3, TNFRSF10B/TRAILR2, SHH, and GLI1, which discriminated those plexiform neurofibromas most likely to undergo malignant transformation. CONCLUSION: Our study has identified a limited number of signaling pathways that could be involved, when altered, in plexiform neurofibroma development. Some of the up-regulated genes could be useful diagnostic or prognostic markers or form the basis of novel therapeutic strategies.

Adolescent↗
PubMed2006

Integrated molecular profiling of SOD2 expression in multiple myeloma.

Reactive oxygen species are known to be involved in several cellular processes, including cell signaling. SOD2 is a key enzyme in the conversion of reactive oxygen species and has been implicated in a host of disease states, including cancer. Using an integrated, whole-cell approach encompassing epigenetics, genomics, and proteomics, we have defined the role of SOD2 in multiple myeloma. We show that the SOD2 promoter is methylated in several cell lines and there is a correlative decrease in expression. Furthermore, myeloma patient samples have decreased SOD2 expression compared with healthy donors. Overexpression of SOD2 results in decreased proliferation and altered sensitivity to 2-methoxyestradiol-induced DNA damage and apoptosis. Genomic profiling revealed regulation of 65 genes, including genes involved in tumorigenesis, and proteomic analysis identified activation of the JAK/STAT pathway. Analysis of nearly 400 activated transcription factors identified 31 transcription factors with altered DNA binding activity, including XBP1, NFAT, forkhead, and GAS binding sites. Integration of data from our gestalt molecular analysis has defined a role for SOD2 in cellular proliferation, JAK/STAT signaling, and regulation of several transcription factors.

2-Methoxyestradiol↗
PubMed2002

High-throughput molecular profiling of high-grade astrocytomas: the utility of fluorescence in situ hybridization on tissue microarrays (TMA-FISH).

Due to recent biological and technical advances, the list of potentially useful candidate genes is rapidly expanding in the study of brain tumors. However, traditional methods of screening individual genes in individual samples are slow and tedious, often with consumption of precious resources after only a few experiments. This study evaluates the feasibility of high-throughput molecular analysis using fluorescence in situ hybridization (FISH) on glioma tissue microarrays (TMA). A single microarray paraffin block was constructed using 65 WHO grade III and IV astrocytomas, sampled in duplicate with 0.6-mm-diameter punch cores. FISH was used to detect common alterations, such as EGFR amplification, chromosome 7, 9, and 10 aneusomies and deletions of 1p, 19q, PTEN, DMBT1, and p16. Of 585 hybridization sets, 508 (87%) yielded interpretable data, with hybridization failure in 33 (5.5%) and dislodged tissue in 44 sets (7.5%), respectively. Glioblastomas harbored significantly more alterations than anaplastic astrocytomas, with the overall frequencies of alterations similar to those reported using other techniques. The overall concordance rate between paired tumor core samples was 93%. We conclude that TMA-FISH is an efficient and reliable method for detecting molecular alterations in high-grade astrocytomas.

Agglutinins↗
PubMed2006

Histopathology in the light of molecular profiling.

The 2001 WHO classification distinguishes five variants (centroblastic, immunoblastic, plasmablastic, anaplastic and T-cell rich) and three subtypes (primary mediastinal, intravascular and primary effusion large B-cell lymphoma) of diffuse large B-cell lymphomas (DLBCLs).The recognition of the three subtypes as distinct disease entities can be considered as an advance in our understanding of these tumours. However, the variants of DLBCLs, which significantly outnumber the subtypes in frequency, represent an unresolved area. Gene expression profiling (GEP) of the variants led to a discrepancy in results and produced more questions than answers. The authors, therefore, initiated a multi-institutional collaborative research project in Germany aimed at a subtle morphologic, genomic and transcriptional characterisation of DLBCLs and Burkitt lymphoma (BL). We included BL in our study for two reasons: (1) it belongs to aggressive B-NHLs; and (2) at present, there are no reliable criteria that can be applied to distinguish BL from DLBCL. The GEPs derived from 200 patient samples were correlated with reviewed histology, the degree of genetic imbalances and clinical features. The results of this approach show that: (i) the DLBCL can be divided into more than four molecular groups; and (ii) the BL cases, identified by the consensus of five out of six lymphoma expert pathologists, displayed a genomic and gene expression profile that was clearly distinct from those of most DLBCLs. The group of DLBCLs that resembled BL in their GEP had a remarkably good prognosis, whereas those that differed in their GEP from the consensus BLs had unfavourable survival rates. In conclusion, combined application of genomic and gene expression profiling in conjunction with consensus reviewed histology and clinical features, appears to be a reliable approach that enables a reproducible and clinically meaningful characterisation of mature aggressive B-NHLs.

Gene Expression Profiling↗
PubMed2001

Molecular profiling of micrometastatic cancer cells.

Malignant tumors of epithelial tissue are the most common form of cancer and are responsible for the majority of cancer-related deaths in Western industrialized countries. As a result of progress in surgical treatment of these tumors, lethality is linked increasingly to early metastasis, which is generally occult at the time of primary diagnosis. For this reason, the direct identification of minimal residual cancer is of particular importance. The studies described below demonstrate the utility of immunocytochemical and molecular analysis in the diagnosis and characterization of minimal residual cancer. These methods not only can identify this critical stage of tumor progression but also may facilitate the development of therapies to prevent manifest metastasis.

Biomarkers, Tumor↗
PubMed2005

Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB.

Giant cell tumor of bone (GCT) is a generally benign, osteolytic neoplasm comprising stromal cells and osteoclast-like giant cells. The osteoclastic cells, which cause bony destruction, are thought to be recruited from normal monocytic pre-osteoclasts by stromal cell expression of the ligand for receptor activator of nuclear factor kappaB (RANKL). This model forms the foundation for clinical trials in GCTs of novel cancer therapeutics targeting RANKL. Using expression profiling, we identified both osteoblast and osteoclast signatures within GCTs, including key regulators of osteoclast differentiation and function such as RANKL, a C-type lectin, osteoprotegerin, and the wnt inhibitor SFRP4. After ex vivo generation of stromal- and osteoclast-enriched cultures, we unexpectedly found that RANKL mRNA and protein were more highly expressed in osteoclasts than in stromal cells, as determined by expression profiling, flow cytometry, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. The expression patterns of molecules implicated in signaling between stromal cells and monocytic osteoclast precursors were analyzed in both primary and fractionated GCTs. Finally, using array-based comparative genomic hybridization, neither GCTs nor the derived stromal cells demonstrated significant genomic gains or losses. These data raise questions regarding the role of RANKL in GCTs that may be relevant to the development of molecularly targeted therapeutics for this disease.

Bone Neoplasms↗