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Biomedical subjects

Ke Chen

Publications and source records attributed to Ke Chen.

At least 19 recordsLinked to original sources
PubMed2026

Natural variation in the PmbHLH162 promoter regulates anthocyanin biosynthesis and accumulation in Prunus mume.

Anthocyanin accumulation is a vital agronomic and ornamental trait, as it not only contributes to adaptation to environmental stress but also enhances ornamental value. In this study, a genome-wide association study (GWAS) was conducted using 328 accessions of mei (Prunus mume) to identify single-nucleotide polymorphisms (SNPs) associated with red pigmentation in petals, filaments, and xylem. Based on these significant SNPs, we defined 2 haplotypes (bHLH162hap1 and bHLH162hap2) and identified PmbHLH162, a bHLH transcription factor gene responsible for anthocyanin biosynthesis regulation. Transient silencing of PmbHLH162 in mei petals via Agrobacterium-mediated transformation resulted in significant color fading, whereas its overexpression dramatically elevated anthocyanin levels. Haplotype analysis showed that 2 promoter variants in bHLH162hap2 (Chr03_2669885 A/C and Chr03_2670272 A/G) alter the binding affinity of transcription factors PmWRKY18 and PmWRKY70. Stronger binding to the G/C alleles gave rise to higher PmbHLH162 expression in bHLH162hap2, thereby promoted red pigmentation in multiple tissues. By contrast, accessions carrying bHLH162hap1 displayed light/colorless phenotype without accumulation of red pigment. Furthermore, PmbHLH162 interacted respectively with PmMYC2, PmTT8, and PmEGL1 to form heterodimers, and markedly enhanced PmMYC2-mediated transcriptional activation of the anthocyanin biosynthetic structural genes PmCHS and PmANS. Geographic haplotype analysis revealed that bHLH162hap2 was predominantly enriched in high-latitude northern populations but was declining markedly at lower latitudes. Collectively, our study reveals the genetic and molecular basis underlying anthocyanin accumulation in mei and identifies a PmbHLH162-PmMYC2 regulatory module in which PmbHLH162 enhances PmMYC2-mediated activation of key anthocyanin biosynthetic genes. The additional interactions of PmbHLH162 with the MBW-associated bHLH factors PmTT8 and PmEGL1 further suggest potential crosstalk between this module and the canonical anthocyanin regulatory network.

Anthocyanins↗
PubMed2026

Immune subtyping of colorectal adenoma identifies a subtype with activated adaptive immunity ahead of progressing to cancer.

BACKGROUND: Colorectal adenomas (CRA) represent precursor lesions with varying risks of malignant transformation. However, molecular subtyping, particularly immune-related classification, remains underexplored in adenomas. This study aims to characterize the immune landscape of CRA through immune subtyping and evaluate its association with cancer progression, gene expression signatures, and functional pathways. METHODS: We conducted a retrospective analysis of transcriptomic data from multiple cohorts of CRA samples. Immune subtypes were identified using non-negative matrix factorization (NMF) based on immune-related genes. Diverse deconvolution algorithms were used to estimate immune cell infiltration. The immune status alteration in premalignant lesion was further consolidated by single-cell transcriptome data. Differential gene expression analysis was performed between subtypes, followed by functional enrichment analyses (Gene Ontology [GO] and Kyoto Encyclopedia of Genes and Genomes [KEGG]). RESULTS: Two distinct immune subtypes were identified: an immune-enriched subtype characterized by high lymphocyte infiltration and elevated expression of immune-related genes, and an immune-deficient subtype with suppressed immune activity. Differential expression analysis revealed significant upregulation of immune response genes (e.g., CD4, CD86, HLA-DRA) in the immune-enriched subtype. GO and KEGG analyses highlighted enrichments in leukocyte transendothelial migration, chemokine signaling, and antigen processing and presentation pathways. Single-cell result revealed an early occurrence of TIGIT activation and exhausted CD8 T cell features in adenoma when compared to normal tissue. CONCLUSION: This study delineates distinct immune subtypes within CRAs. The immune-enriched subtype demonstrates activated adaptive immunity and may reflect a higher potential for immune surveillance, while the immune-deficient subtype exhibits stromal features suggestive of progressive transformation. These findings provide insights into early immune microenvironment alterations and may inform strategies for risk stratification and immunoprevention in colorectal carcinogenesis.

Colorectal adenoma↗
PubMed2026

Embryophyte-wide detection of natural Agrobacterium-mediated horizontal gene transfer reveals an ancient role for mini T-DNAs.

Agrobacterium transfers DNA into plant cells, leading to tumors, hairy roots (HR), and natural genetically modified organisms (nGMOs). Transferred DNAs (T-DNAs) from agrobacteria and T-DNA-derived cellular T-DNAs (cT-DNAs) from nGMOs vary considerably and may carry up to 15 different genes. Among these, opine synthase (ops) genes encode the synthesis of opines used as nutrients by the agrobacteria. Earlier studies predicted large numbers of naturally transformed plant species, but only few have been identified and studied so far. We therefore developed a general method to detect cT-DNAs in all publicly available whole genome sequences (WGS) and Sequence Read Archive (SRA) data from land plants. To avoid false positives, we only retained DNA sequences coding for T-DNA proteins. A total of 2614 nGMO species were identified, most are eudicots. However, cT-DNAs were also found in 82 mosses and 75 ferns, showing that Agrobacterium can also generate natural transformants among the early land plants. Analysis of 149 cT-DNA maps revealed different types of T-DNAs. Most notably, these included small T-DNAs (mini T-DNAs) with a single opine synthase gene. Mini T-DNAs are not expected to induce tumors or HRs. The predominance of mini cT-DNAs in mosses and ferns, and the presence of more complex cT-DNAs in spermatophytes, indicate that mini T-DNAs represent the earliest types of T-DNA. Our study also detected unusual T-DNA integration patterns, with multiple copies spread out over several hundreds of kilobases.

DNA, Bacterial↗
PubMed2025

Laboratory Evolution Reveals Transcriptional Mechanisms Underlying Thermal Adaptation of Escherichia coli.

Adaptive laboratory evolution is able to generate microbial strains, which exhibit extreme phenotypes, revealing fundamental biological adaptation mechanisms. Here, we use adaptive laboratory evolution to evolve Escherichia coli strains that grow at temperatures as high as 45.3 °C, a temperature lethal to wild-type cells. The strains adopted a hypermutator phenotype and employed multiple systems-level adaptations that made global analysis of the DNA mutations difficult. Given the challenge at the genomic level, we were motivated to uncover high-temperature tolerance adaptation mechanisms at the transcriptomic level. We employed independently modulated gene set (iModulon) analysis to reveal five transcriptional mechanisms underlying growth at high temperatures. These mechanisms were connected to acquired mutations, changes in transcriptome composition, sensory inputs, phenotypes, and protein structures. They are as follows: (i) downregulation of general stress responses while upregulating the specific heat stress responses, (ii) upregulation of flagellar basal bodies without upregulating motility and upregulation fimbriae, (iii) shift toward anaerobic metabolism, (iv) shift in regulation of iron uptake away from siderophore production, and (v) upregulation of yjfIJKL, a novel heat tolerance operon whose structures we predicted with AlphaFold. iModulons associated with these five mechanisms explain nearly half of all variance in the gene expression in the adapted strains. These thermotolerance strategies reveal that optimal coordination of known stress responses and metabolism can be achieved with a small number of regulatory mutations and may suggest a new role for large protein export systems. Adaptive laboratory evolution with transcriptomic characterization is a productive approach for elucidating and interpreting adaptation to otherwise lethal stresses.

Escherichia coli↗
PubMed2025

Accumulation of numerous cellular T-DNA sequences in the genus Diospyros by multiple rounds of natural transformation.

Horizontal gene transfer (HGT) is an important phenomenon in the evolutionary history of plants. Natural transformation by Agrobacterium is a special case of HGT and leads to the insertion of cellular T-DNA (cT-DNA) sequences, for example, in Diospyros lotus. The genus Diospyros contains about 795 species with economically important members, like different types of persimmon (D. kaki, D. lotus, and D. virginiana) and ebony (e.g., D. ebenum). Whole genome sequences (WGS) from D. kaki, D. oleifera, D. lotus, and D. virginiana were investigated for cT-DNAs. These four species belong to one clade and contain 15 different cT-DNAs (DiTA to DiTO). The hexaploid species D. kaki cv. "Xiaoguo-tianshi" contains seven types of cT-DNA (DiTA to DiTG) on 27 of 42 homeologs, adding up to 628 kb of cT-DNA. Five of these seven cT-DNAs are non-fixed, as shown by empty chromosomal insertion sites. The evolutionary history of the Diospyros cT-DNAs was reconstructed using the divergence of their inverted repeats. Insert age varied from 3 to 12 million years. Partial cT-DNA sequences were detected in 35 additional species from five Diospyros clades. Our data highlight the unexpectedly large scale of natural Agrobacterium transformation in Diospyros and demonstrate the necessity of whole genome approaches for studies on the origin and evolution of cT-DNAs.

Diospyros↗
PubMed2006

[Curcumin-induced the expression of inhibitor kappaBalpha protein in human prostate cancer cells].

OBJECTIVE: To investigate the curcumin-induced the expression of IkappaBalpha in androgen-dependent (LNCaP) and androgen-independent (PC3) prostate cancer cells, and to study the mechanisms of curcumin on the proliferative inhibition of prostate cancer cells. METHODS: After LNCaP and PC3 cells were affected by 10, 25, 50, 75, 100 micromol/L curcumin respectively, the cell activity was assayed with methyl thiazolyl tetrazolium (MTT) method at 5, 12 and 24 hours; Flow cytometry was adopted to observe the cell cycle of LNCaP and PC3 cells at 24 hours. After 5 hours, the expression of IkappaBalpha in LNCaP and PC3 cells was observed with Western blotting. RESULTS: Curcumin obviously suppressed the proliferation of LNCaP and PC3 cells in does-dependent and time-dependent manners. Curcumin could arrest the cell cycle of LNCaP and PC3 cells at G(2), M phase and then induce cell apoptosis. The expression of IkappaBalpha in LNCaP cells had no significant difference after using curcumin (F = 0.129, P > 0.05). However, the expression of IkappaBalpha in PC3 cells increased gradually with the inducement of concentration-increased curcumin (F = 31.618, P < 0.05). CONCLUSIONS: IkappaBalpha may play a role in the curcumin inducing apoptosis of PC3 cell, while the curcumin inducing apoptosis of LNCaP cells is by antioxidation and inhibiting metabolites formation in LNCaP cells.

Apoptosis↗
PubMed2006

Induction of leptin resistance through direct interaction of C-reactive protein with leptin.

The mechanisms underlying leptin resistance are still being defined. We report here the presence in human blood of several serum leptin-interacting proteins (SLIPs), isolated by leptin-affinity chromatography and identified by mass spectrometry and immunochemical analysis. We confirmed that one of the major SLIPs is C-reactive protein (CRP). In vitro, human CRP directly inhibits the binding of leptin to its receptors and blocks its ability to signal in cultured cells. In vivo, infusion of human CRP into ob/ob mice blocked the effects of leptin upon satiety and weight reduction. In mice that express a transgene encoding human CRP, the actions of human leptin were completely blunted. We also found that physiological concentrations of leptin can stimulate expression of CRP in human primary hepatocytes. Recently, human CRP has been correlated with increased adiposity and plasma leptin. Thus, our results suggest a potential mechanism contributing to leptin resistance, by which circulating CRP binds to leptin and attenuates its physiological functions.

Animals↗
PubMed2006

Expression of human DEC-205 (CD205) multilectin receptor on leukocytes.

DEC-205 (CD205) belongs to the macrophage mannose receptor family of C-type lectin endocytic receptors and behaves as an antigen uptake/processing receptor for dendritic cells (DC). To investigate DEC-205 tissue distribution in human leukocytes, we generated a series of anti-human DEC-205 monoclonal antibodies (MMRI-5, 6 and 7), which recognized epitopes within the C-type lectin-like domains 1 and 2, and the MMRI-7 immunoprecipitated a single approximately 200 kDa band, identified as DEC-205 by mass spectrometry. MMRI-7 and another DEC-205 mAb (MG38), which recognized the epitope within the DEC-205 cysteine-rich and fibronectin type II domain, were used to examine DEC-205 expression by human leukocytes. Unlike mouse DEC-205, which is reported to have predominant expression on DC, human DEC-205 was detected by flow cytometry at relatively high levels on myeloid blood DC and monocytes, at moderate levels on B lymphocytes and at low levels on NK cells, plasmacytoid blood DC and T lymphocytes. MMRI-7 F(ab')2 also labeled monocytes, B lymphocytes and NK cells similarly excluding reactivity due to non-specific binding of the mAb to FcgammaR. Tonsil mononuclear cells showed a similar distribution of DEC-205 staining on the leukocytes. DEC-205-specific semiquantitative immunoprecipitation/western blot and quantitative reverse transcriptase-PCR analysis established that these leukocyte populations expressed DEC-205 protein and the cognate mRNA. Thus, human DEC-205 is expressed on more leukocyte populations than that were previously assumed based on mouse DEC-205 tissue localization studies. The broader DEC-205 tissue expression in man is relevant to clinical DC targeting strategies and DEC-205 functional studies.

Animals↗
PubMed2006

Compression-inhibited pore formation of polyelectrolyte multilayers containing weak polyanions: a scanning force microscopy study.

Morphological changes of poly(acrylic acid)/poly(diallyldimethylammonium chloride) multilayers induced by low pH were investigated by scanning force microscopy. The weakened interaction between the charged polymer chains in the protonation process is believed to be the reason for this variation. Kinetic studies have shown that during protonation phase separation and dissociation of the multilayers took place successively. The compression of the multilayers, however, caused a transition of the multilayers from a rubbery state to a glassy state. As a result, the closely compacted multilayers lost their sensitivity to pH change. An increase of electrostatic and hydrophobic interactions, can decrease the free energy of the multilayers, and stabilize the films. By compression of the multilayers with a rubber stamp having geometric patterns, films with spatially localized pores were produced.

Journal Article↗
PubMed2006

Prediction of three dimensional structure of calmodulin.

Calmodulin (CaM) is an important human protein, which has multiple structures. Numerous researchers studied the CaM structures in the past, and about 50 different structures in complex with fragments derived from CaM-regulated proteins have been discovered. Discovery and analysis of existing and new CaM structures is difficult due to the inherent complexity, i.e. flexibility of 6 loops and a central linker that constitute part of the CaM structure. The extensive interest in CaM structure analysis and discovery calls for a comprehensive study, which based on the accumulated expertise would design a method for prediction and analysis of future and existing CaM structures. It is also important to find the mechanisms by which the protein adjusts its structure with respect to various factors. To this end, this paper analyzes the known CaM structures and finds four factors that influence CaM structure, which include existence of Ca2+ binding, different binding segments, measuring surroundings, and sequence mutation. The degree of influence of specific factors on different structural regions is also investigated. Based on the analysis of the relation between the four factors and the corresponding CaM structure a novel method for prediction of the CaM structure in complex with novel segments, given that the surroundings of the complex, is developed. The developed prediction method is tested on a set aside, newest CaM structure. The prediction results provide useful and accurate information about the structure verifying high quality of the proposed prediction method and performed structural analysis.

Amino Acid Sequence↗
PubMed2006

Quantitative analysis of the conservation of the tertiary structure of protein segments.

The publication of the crystallographic structure of calmodulin protein has offered an example leading us to believe that it is possible for many protein sequence segments to exhibit multiple 3D structures referred to as multi-structural segments. To this end, this paper presents statistical analysis of uniqueness of the 3D-structure of all possible protein sequence segments stored in the Protein Data Bank (PDB, Jan. of 2003, release 103) that occur at least twice and whose lengths are greater than 10 amino acids (AAs). We refined the set of segments by choosing only those that are not parts of longer segments, which resulted in 9297 segments called a sponge set. By adding 8197 signature segments, which occur uniquely in the PDB, into the sponge set we have generated a benchmark set. Statistical analysis of the sponge set demonstrates that rotating, missing and disarranging operations described in the text, result in the segments becoming multi-structural. It turns out that missing segments do not exhibit a change of shape in the 3D-structure of a multi-structural segment. We use the root mean square distance for unit vector sequence (URMSD) as an improved measure to describe the characteristics of hinge rotations, missing, and disarranging segments. We estimated the rate of occurrence for rotating and disarranging segments in the sponge set and divided it by the number of sequences in the benchmark set which is found to be less than 0.85%. Since two of the structure changing operations concern negligible number of segment and the third one is found not to have impact on the structure, we conclude that the 3D-structure of proteins is conserved statistically for more than 98% of the segments. At the same time, the remaining 2% of the sequences may pose problems for the sequence alignment based structure prediction methods.

Amino Acid Sequence↗
PubMed2006

Chitosan-mediated synthesis of gold nanoparticles on patterned poly(dimethylsiloxane) surfaces.

Synthesis of gold nanoparticles on surfaces has been accomplished by the incubation of poly(dimethylsiloxane) (PDMS) films in tetrachloroauric(III) acid and chitosan solution at room temperature and 4 degrees C. One important point in the present study is that the synthesis selectively occurred on the PDMS surface. These observations are substantially different from the reaction in solution, in which no particles can be formed at room temperature. Computation of surface plasmon bands (SPBs) based on Mie theory suggests that the particles are partially coated by chitosan molecules, and the experimental results confirm the theoretical calculations. The proposed mechanism is that chitosan molecules adsorbed or printed on the PDMS surfaces act as reducing/stabilizing agents. Furthermore, PDMS films patterned with chitosan could induce localized synthesis of gold nanoparticles in regions capped with chitosan only. In this way, colloidal patterns were fabricated on the surfaces with high spatial selectivity simultaneously with the synthesis of the particles. Surface-induced fluorescence quenching was observed in the regions capped with gold nanoparticles as well.

Chitosan↗
PubMed2006

Diabetes mellitus in individuals with spinal cord injury or disorder.

BACKGROUND/OBJECTIVE: To examine diabetes prevalence, care, complications, and characteristics of veterans with a spinal cord injury or disorder (SCI/D). METHODS: A national survey of veterans with an SCI/D was conducted using Behavioral Risk Factor Surveillance System (BRFSS) survey questions. Data were compared with national Centers for Disease Control and Prevention BRFSS data for veteran and nonveteran general populations. RESULTS: Overall prevalence of diabetes in individuals with an SCI/D was 20% (3 times higher than in the general population). Veterans with an SCI/D and veterans, in general, had a higher prevalence of diabetes across all age groups; however, those with an SCI/D who were 45 to 59 years of age had a higher prevalence than other veterans. One fourth of the persons with an SCI/D and diabetes reported that diabetes affected their eyes or that they had retinopathy (25%), and 41% had foot sores that took more than 4 weeks to heal. More veterans, both with (63%) and without an SCI/D (60%), took a class on how to manage their diabetes than the general population (50%). Veterans with an SCI/D and diabetes were more likely to report other chronic conditions and poorer quality of life than those without diabetes. CONCLUSIONS: Diabetes prevalence is greater among veterans with an SCI/D compared with the civilian population, but is similar to that of other veterans, although it may occur at a younger age in those with an SCI/D. Veterans with an SCI/D and diabetes reported more comorbidities, more slow-healing foot sores, and poorer quality of life than those without diabetes. Efforts to prevent diabetes and to provide early intervention in persons with SCI/D are needed.

Adult↗
PubMed2006

Disease prevalence and use of preventive services: comparison of female veterans in general and those with spinal cord injuries and disorders.

BACKGROUND: Disease prevalence and use of preventive services may differ between women veterans in general and those with spinal cord injuries and disorders (SCI&D). Prevention is particularly important in SCI&D, and disparities may exist in receipt of this care, particularly when special equipment and body adjustments are needed, among women with SCI&D. METHODS: To compare disease prevalence and preventive service use among female veterans in general and those with SCI&D, we conducted a cross-sectional survey among female veterans in general (n = 478) and those with SCI&D (n = 115). Behavioral Risk Factor Surveillance System (BRFSS) survey questions were administered to veterans with SCI&D and compared with 2003 CDC BRFSS data. RESULTS: Female veterans with SCI&D were similar in age and race but were better educated and less likely to be employed than female veterans in general. Coronary heart disease (CHD) prevalence was higher in those with SCI&D (17% vs. 8%, p < 0.0001). Health status was lower in SCI&D (27%) than in general female veterans (41%), p = 0.002. Fewer women with SCI&D, than female veterans in general reported having received recommended dental care (56% vs. 69%, p = 0.004), colon screening in prior 5 years (59% vs. 72%, p = 0.023) or prior 10 years (67% vs. 92%, p< 0.0001), mammogram (84% vs. 91%, p = 0.019), and Pap smear (88% vs. 98%, p < 0.0001). There were no differences in receipt of respiratory vaccinations or cholesterol screening. CONCLUSIONS: Receipt of services that require the use of equipment, body adjustments, and potential discomfort due to disability was lower in women with SCI&D. Veterans Affairs (VA) is doing well in most areas, but there are gaps in receipt of some preventive services. Efforts to increase preventive care in women with SCI&D should address equipment and access barriers and patient and provider education.

Adult↗
PubMed2006

[Curcumin-induced apoptosis in androgen-dependent prostate cancer cell line LNCaP in vitro].

OBJECTIVE: To explore the apoptosis induction by curcumin in androgen-dependent prostate cancer cell line LNCaP). METHODS: After LNCaP cells were induced by 10, 25, 50, 75, 100 micromol/L curcumin respectively, the cell activity was assayed by MTT at 5, 12 and 24 hours. Flow cytometry and electronic microscopy were adopted to observe cell cycle and morphological changes of LNCaP cells at 24 hours. After 5 hours, the expression of IkappaBalpha in LNCaP cells was detected by Western blotting. RESULTS: The growth of LNCaP cells was suppressed obviously by curcumin in dose-dependent and time-dependent manners in vitro. There were significant differences in inhibition rate among different concentrations and time groups (P < 0.05). Furthermore, curcumin could arrest the cell cycle of LNCaP cells at G2/M phase in a dose-dependent manner (P <0.01). The ratios of apoptosis were significantly higher than those of controls (P < 0. 5). Curcumin could lead to characteristic morphological changes of apoptosis in LNCaP cells after 24 hours. The expression of IkappaBalpha in LNCaP cell did not show marked changes after the exposure to different concentrations of curcumin within 5 hours. CONCLUSION: Curcumin can suppress the growth of LNCaP, and promotes their apoptosis.

Apoptosis↗
PubMed2005

Complex PbTe hopper (skeletal) crystals with high hierarchy.

A facile and mild solution method has been discovered for the synthesis of complex PbTe hopper crystals in large quantities, which are highly similar to the cubic halite skeletal crystals formed from extreme supersaturation in salt lakes existing in nature. This route may provide a new approach to growing other complex semiconductor structures of high hierarchy.

Journal Article↗
PubMed2005

Prophylactic, therapeutic and anti-metastatic effects of an HPV-16mE6Delta/mE7/TBhsp70Delta fusion protein vaccine in an animal model.

Human papillomaviruses (HPVs), particularly HPV-16, are not only causally linked to cervical cancers but also play an important role in the development of other cancers. The oncoproteins, E6 and E7, are consistently coexpressed in the majority of HPV-containing carcinomas and their metastatic lesions, and are critical to the induction and maintenance of malignant phenotype, and also can cause tumor metastasis. Therefore, E6 and E7 represent ideal tumor-specific antigens for the development of immunotherapy to prevent and treat HPV-associated cancers and their metastases. The powerful antigenic nature of Mycobacterium tuberculosis heat shock protein 70 (TBhsp70) is emphasized by evidence that mammals are capable of recognizing murine and human multiple B and T cell epitopes in this protein, and therefore allows it to be used as an adjuvant-free carrier to stimulate the immune response to a covalently linked fusion partner. In our present study, we developed a recombinant TBhsp70Delta protein expression vector that permits the production of other protein fused to TBhsp70Delta. A recombinant HPV-16mE6Delta/mE7/TBhsp70Delta fusion protein was expressed and purified, and immunization with the fusion protein in the absence of adjuvant was capable of providing strong protection to C57BL/6 mice against challenge and rechallenge with TC-1 cells, but not HPV negative Lewis lung cancer cells, and induced established TC-1 tumor regression and led to long-term survival. Consistent with the in vivo results, the fusion protein immunization in the absence of adjuvant induced cytolytic T lymphocytes recognized specifically TC-1 tumor cells in vitro. We also demonstrated that immunization with the fusion protein in the absence of adjuvant was effective in both preventing and treating TC-1 metastatic lesions in the lung metastasis model. In particular, immunization with the fusion protein caused regression of established lung metastatic lesions in 50% of immunized animals. This study represents an instance of tumor therapy with a TBhsp70Delta fusion protein and provides the scientific basis for the clinical application of the HPV16mE6Delta/mE7/TBhsp70Delta fusion protein in the treatment of HPV-associated cancers and their metastases.

Animals↗