Biomedical subjects

T Spruss

Publications and source records attributed to T Spruss.

At least 19 recordsLinked to original sources

PubMed2001

Programmable biodegradable implants.

Pulsatile release implants were developed that release substances up to 58 days post implantation. With a cylindrical size of 2 mm diameter and 1.8 mm height the matrices can carry as much as 1 mg of drug and allow even for intracranial implantation into a rodent model. The matrices are made of materials that have been used for parenteral applications in humans before such as surface eroding polyanhydrides and bulk eroding poly(D,L-lactic acid) or poly(D,L-lactic acid-co-glycolic acid). The onset of drug release is controlled by the degradation of bulk eroding polymers which are known to exhibit a certain stability over a defined period of time and which start eroding after they reach a critical degree of degradation. The time of drug release onset was found to depend on the molecular weight and the chemical state of the carboxylic acid end of the polymer chain. For testing the onset of release in vivo a nude mouse model was developed where the release of Evan's blue could be observed visually after subcutaneous application. By combining individual matrices with different release onset, a therapeutic system can be composed that releases drugs after implantation at predetermined time points in a preprogrammed way. Potential applications for such matrices is vaccination and local tumor therapy.

Absorbable Implants↗

PubMed2001

1-(2,6-dichloro-4-hydroxyphenyl)-2-phenylethanes--new biological response modifiers for the therapy of breast cancer. Synthesis and evaluation of estrogenic/antiestrogenic properties.

[meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-1-PtLL'; L,L' = Cl or L = H2O and L' = OSO3) are highly effective towards hormone-sensitive, rodent breast cancers due to their significant estrogenic potencies. Their antitumor activities are caused by modification of the immune response. The pharmacophor of these compounds, the 1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethane (23H), was used as the lead structure in a structure-activity study with the goal of finding new biological response modifiers for the therapy of breast cancer. As intermediates for the synthesis of the 23H derivatives, the CH3O-substituted stilbenes 12E/12Z-16E/16Z were prepared by reaction of the related benzyltriphenylphosphonium halides with 2,6-dichloro-4-methoxybenzaldehyde by the method of Wittig/Campbell and Donald, respectively. Separation of the E/Z-mixtures was performed by fractional crystallization and/or column chromatography. The E-1,2-bis(2,6-dichloro-4-methoxyphenyl)ethene (17E) was obtained by reductive coupling of 2,6-dichloro-4-methoxybenzaldehyde with TiCl4/Zn according to the method of Mukaiyama. Illumination of the solution of 17E in benzene with UV light resulted in an E/Z-isomerization. Compound 17Z could be isolated from this mixture. The CH3O-substituted stilbenes were transformed into their 1,2-diphenylethanes (12H-17H) by catalytic hydrogenation of the C1=C2 double bond. Ether cleavage of the compounds was performed with BBr3. In the estrogen receptor binding assay all OH-substituted 1,2-diphenylethanes showed affinity to the estrogen receptor, which was about two orders of magnitude lower than that of 17 beta-estradiol. In the uterus weight test on the immature mouse 1,2-diphenylethanes with 4-substituted OH groups proved to be "true" estrogens (19H: 2-F/4-OH; 20H: 2-Cl/4-OH; 23H: 2,6-Cl2/4-OH), while those with a 3-substituted OH group in the 2-phenyl ring showed the properties of a "partial" estrogen (18H: 3-OH) or of an "impeded" estrogen (21H: 2-Cl/3-OH; 22H: 2-Cl/5-OH). The latter also showed significant additional antiestrogenic activity. The related E-stilbenes mostly exhibit similar hormonal activities. As a rule, the replacement of the OH groups by the CH3O groups and the change from the E- to the Z-configuration led to a reduction of the estrogenic potencies. Several of the 1-(2,6-dichloro-4-methoxyphenyl)-2-phenylethenes (12E: 3-OCH3; 12Z: 3-OCH3; 15E: 2-Cl/3-OCH3; 15Z: 2-Cl/3-OCH3; 16E: 2-Cl/5-OCH3) produced antiestrogenic effects in the uterus weight test. It is supposed that those new 1-(2,6-dichloro-4-hydroxyphenyl)-2-phenylethanes endowed with marked estrogenic properties are also active as biological response modifiers in animals bearing hormone-sensitive breast cancer. The antiestrogenic derivatives presumably inhibit the breast cancer development by competing with tumor growth stimulating endogenous estrogens for the binding to the receptor. This is to be confirmed in a further study.

Animals↗

PubMed2001

Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) act as an immune response modifier? IV. Inhibition of the proliferation-increasing effect of progressively growing MXT-M-3,2 breast cancer on phagocytes by the title compound.

In female B6D2F1 mice bearing an MXT-M-3,2 breast cancer graft the level of the phagocytic cells (e.g. of granulocytes and macrophages in the spleen and of granulocytes and monocytes in the blood) is significantly elevated. The positive correlation between the number of the phagocytic cells and the weight of the tumor indicates that the MXT-M-3,2 breast cancer promotes myelopoiesis, presumably by secretion of hematopoietic growth factors like GM-CSF. This process can be described for each phagocyte type by a regression equation. Due to its hormonal potency [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) (meso-1-PtCl2) can reduce the excessive numbers of the granulocytes and macrophages, which seem to be responsible for the progressive growth of the MXT-M-3,2 breast cancer. This process leads to an interruption of the vicious circle of mutual growth stimulation of breast cancer cells and these phagocytes. The target of meso-1-PtCl2 is the estrogen receptor (ER) of the breast cancer cell. The interaction between meso-1-PtCl2 and the ER presumably results in a diminished secretion of hematopoietic growth factors and hence in a decline of the number of phagocytic cells. Meso-1-PtCl2 does not inhibit the proliferation of tumor cells by direct interaction with their DNA, as is described for platinum complexes like cDDP. In its mode of action the equipotent, breast cancer inhibiting drug cDDP differs from meso-1-PtCl2. This is obvious from the fact that in cDDP--but not in meso-1-PtCl2-treated, tumor bearing mice the number of granulocytes and macrophages does not markedly deviate from that in untreated control mice with tumors of the same weight. The drug cDDP probably does not interfere with the mechanism of the secretion of hematopoietic growth factors. The reduction of the number of tumor cells by cDDP leads to a decline of the number of phagocytic cells in accordance with the respective regression equations. In contrast to meso-1-PtCl2 and cDDP, ovariectomy causes elevated phagocyte numbers, probably due to the strongly reduced estrogen level. The studies described in this publication indicate that the anti-breast cancer activity of meso-1-PtCl2 is caused by a decimation of phagocytes and with this by an abolition of the tumor promoting effect. Furthermore, a restoration of the natural immunosurveillance seems to be of importance.

Adjuvants, Immunologic↗

PubMed2001

"Hit-and-run" transformation by adenovirus oncogenes.

According to classical concepts of viral oncogenesis, the persistence of virus-specific oncogenes is required to maintain the transformed cellular phenotype. In contrast, the "hit-and-run" hypothesis claims that viruses can mediate cellular transformation through an initial "hit," while maintenance of the transformed state is compatible with the loss ("run") of viral molecules. It is well established that the adenovirus E1A and E1B gene products can cooperatively transform primary human and rodent cells to a tumorigenic phenotype and that these cells permanently express the viral oncogenes. Additionally, recent studies have shown that the adenovirus E4 region encodes two novel oncoproteins, the products of E4orf6 and E4orf3, which cooperate with the viral E1A proteins to transform primary rat cells in an E1B-like fashion. Unexpectedly, however, cells transformed by E1A and either E4orf6 or E4orf3 fail to express the viral E4 gene products, and only a subset contain E1A proteins. In fact, the majority of these cells lack E4- and E1A-specific DNA sequences, indicating that transformation occurred through a hit-and-run mechanism. We provide evidence that the unusual transforming activities of the adenoviral oncoproteins may be due to their mutagenic potential. Our results strongly support the possibility that even tumors that lack any detectable virus-specific molecules can be of viral origin, which could have a significant impact on the use of adenoviral vectors for gene therapy.

Adenoviridae↗

PubMed2001

The induction of micronuclei in vitro by unpolymerized resin monomers.

Components of resin materials may damage DNA, leading to genetic alterations in mammalian cells. Here, monomers were analyzed for the induction of chromosomal aberrations indicated by micronuclei induced in V79 cells. A dose-related increase in the numbers of micronuclei was observed with triethyleneglycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and glycidyl methacrylate (GMA). These effects were reduced, however, by a metabolically active microsomal fraction from rat liver. The very low activity of Bis-GMA and UDMA and the elevated numbers of micronuclei caused by high concentrations of methyl methacrylate and bisphenol A were associated with cytotoxicity. Our findings provide evidence for the induction of micronuclei by TEGDMA, HEMA, and GMA under physiological conditions, indicating clastogenic activity of these chemicals in vitro. Since it has been shown that TEGDMA also caused gene mutations and DNA sequence deletions in mammalian cells, the activity of this substance should be analyzed in vivo.

Acrylic Resins↗

PubMed2000

Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II) act on the hormone-sensitive, murine breast cancer as a biological response modifier? Part 1: The MXT-M-3.2 breast cancer stimulates the growth of an identical second graft; [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplat inum (II) inhibits this process.

The MXT-M-3.2 breast cancer implanted into female B6D2F1 mice accelerates the growth of an identical second tumor. This process is inhibited by [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II). The possible modes of action of this compound as a biological response modifier are discussed.

Animals↗

PubMed2000

Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II) act on the hormone-sensitive, murine breast cancer as a biological response modifier? Part II. Studies on the influence of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] dichloroplatinum(II) on the specific immune defense in MXT-M-3,2 breast cancer bearing mice.

The anti-tumor activity of [meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) on the MXT-M-3,2 breast cancer implanted into B6D2F1 mice was not significantly reduced by splenectomy or co-administration of cyclosporine A. Neither did the use of T-lymphocyte-deficient NMRI (nu/nu) mice as hosts substantially influence its anti-tumor effect. Obviously, [meso-1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]dichloroplatinum(II) does not act by an enhancement of the specific immune defense.

Animals↗

PubMed2000

Does [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloro-platinum(II) act as an immune response modifier? Part III: Progressively growing MXT-M-3,2 breast cancer stimulates the proliferation of phagocytes in B6D2F1 mice.

MXT-M-3,2 breast cancer implanted into female B6D2F1 mice accelerates the growth of an identical second tumor. This process is accompanied by a significant increase of the granulocyte and monocyte numbers in the blood and of the granulocyte and macrophage numbers in the spleen. A significant positive correlation of strong intensity was found between the tumor weight on the one hand and the number of the granulocytes and macrophages on the other hand. The tumor-dependent promotion of the myelopoiesis is explained with a secretion of hematopoietic growth factors, e.g. of the granulocyte-macrophage-stimulating growth factor (GM-CSF), by the breast cancer cells.

Animals↗

PubMed2000

Establishment and characterization of the follicular thyroid carcinoma cell line ML-1.

The present study focuses on the establishment and characterization of a new follicular thyroid carcinoma cell line. The human cell line ML-1 was derived from a dedifferentiated follicular thyroid carcinoma relapse, which progressed despite preceding surgery followed by two radioiodine therapies. More than 90% of the cells of this line express thyroglobulin, chondroitin sulfate, and vimentin antigens, but only about 70% show cytokeratin filaments and a negative surface charge density such as human erythrocytes. More importantly, cells of this line are able to take up iodine and/or glucose both in vitro and in vivo and to secrete thyroglobulin, chondroitin sulfate, and fibronectin into the interstitial space. In addition, triiodothyronine is released constitutively into culture supernatants. Moreover, it is also suitable for xenotransplantation studies because it is tumorigenic in NMRI nude mice in vivo. The cell line forms tumors with follicular structures when transplanted to nude mice. Due to these unique features the ML-1 cell line can be considered as a very suitable test model for pharmacological and cell biological studies. Since chemicals may interfere with the production of thyroid hormones, this cell line represents also a tool for toxicological investigations.

Adenocarcinoma, Follicular↗

PubMed2000

Transport of lipids from golgi to plasma membrane is defective in tangier disease patients and Abc1-deficient mice.

Mutations in the gene encoding ATP-binding cassette transporter 1 ( ABC1) have been reported in Tangier disease (TD), an autosomal recessive disorder that is characterized by almost complete absence of plasma high-density lipoprotein (HDL), deposition of cholesteryl esters in the reticulo-endothelial system (RES) and aberrant cellular lipid trafficking. We demonstrate here that mice with a targeted inactivation of Abc1 display morphologic abnormalities and perturbations in their lipoprotein metabolism concordant with TD. ABC1 is expressed on the plasma membrane and the Golgi complex, mediates apo-AI associated export of cholesterol and phospholipids from the cell, and is regulated by cholesterol flux. Structural and functional abnormalities in caveolar processing and the trans-Golgi secretory pathway of cells lacking functional ABC1 indicate that lipid export processes involving vesicular budding between the Golgi and the plasma membrane are severely disturbed.

ATP Binding Cassette Transporter 1↗

PubMed2000

Two distinct activities contribute to the oncogenic potential of the adenovirus type 5 E4orf6 protein.

Previous studies have shown that the adenovirus type 5 (Ad5) E4orf6 gene product displays features of a viral oncoprotein. It initiates focal transformation of primary rat cells in cooperation with Ad5 E1 genes and confers multiple additional transformed properties on E1-expressing cells, including profound morphological alterations and dramatically accelerated tumor growth in nude mice. It has been reported that E4orf6 binds to p53 and, in the presence of the Ad5 E1B-55kDa protein, antagonizes p53 stability by targeting the tumor suppressor protein for active degradation. In the present study, we performed a comprehensive mutant analysis to assign transforming functions of E4orf6 to distinct regions within the viral polypeptide and to analyze a possible correlation between E4orf6-dependent p53 degradation and oncogenesis. Our results show that p53 destabilization maps to multiple regions within both amino- and carboxy-terminal parts of the viral protein and widely cosegregates with E4orf6-dependent acceleration of tumor growth, indicating that both effects are related. In contrast, promotion of focus formation and morphological transformation require only a carboxy-terminal segment of the E4 protein. Thus, these effects are completely independent of p53 stability, but may involve other interactions with the tumor suppressor. Our results demonstrate that at least two distinct activities contribute to the oncogenic potential of Ad5 E4orf6. Although genetically separable, both activities are largely mediated through a novel highly conserved, cysteine-rich motif and a recently described arginine-faced amphipathic alpha helix, which resides within a carboxy-terminal "oncodomain" of the viral protein.

Adenovirus E1A Proteins↗

PubMed1999

The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53.

The adenovirus type 5 (Ad5) E4orf6 protein promotes focus formation of primary baby rat kidney (BRK) cells in cooperation with Ad5 E1 proteins. This activity is most likely related to the ability of the E4orf6 protein to bind to p53 and modulate its tumor suppressor functions. In this study we report that transformed BRK cells that stably express E4orf6 in addition to E1A and E1B (ABS cells) displayed multiple additional properties commonly associated with a high grade of oncogenic transformation compared to cells expressing only E1A and E1B (AB cells). These properties included morphological alterations, markedly enhanced growth rates and growth to much higher saturation densities. Following injection into nude mice ABS-derived tumors exhibited accelerated growth and, based on histopathological criteria, proofed to be much more malignant compared to tumors generated by AB cells. Interestingly, these highly transformed properties of ABS cells correlated with a dramatic reduction of p53 steady-state levels which inversely correlated with E4orf6 expression. From these results we conclude that expression of the Ad5 E4orf6 protein (i) confers additional transformed in vitro properties to primary rat cells expressing the Ad5 E1 proteins, and (ii) increases the tumorigenic and malignant potential of these cells in vivo. Our data suggest that the Ad5 E4orf6 protein enhances the intrinsic ability of E1-transformed rat cells to grow in a neoplastic state by completely inactivating p53 tumor suppressor function in combination with the E1A and E1B proteins.

Adenovirus E1A Proteins↗

PubMed1999

[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II), a compound with a specific activity on hormone-sensitive breast cancers--evidence for a diethylstilbestrol-like mode of action.

[meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II) (meso-1-PtCl2), an estrogenic and cytotoxic platinum complex, shows activity against ER+ but not against ER- breast cancers in vivo (ER: estrogen receptor; ER+ and ER- indicate the presence or absence of the ER). To clarify whether its estrogenic or its cytotoxic potency or both properties are the cause of this specific inhibitory effect, we tested meso-1-PtCl2 comparatively in vivo on an ER+ and an ER- murine breast cancer (MXT-M-3.2 MC and MXT-M-3.2(ovex) MC, respectively), and in vitro on two cell lines derived from the former in vivo models (MXT+ and MXT-, respectively). The estrogens diethylstilbestrol (DES) and the ligand of meso-1-PtCl2 (meso-1), responsible for the hormonal effect of meso-1-PtCl2, and the cytotoxic drug cisplatin (cDDP) were used as comparative substances. Meso-1-PtCl2. DES and cDDP showed a strong and comparable activity on the ER+ MXT-M-3.2 MC in vivo, meso-1 being somewhat less inhibitory. In experiments on the murine, ER- MXT-M-3.2(ovex) MC only cDDP caused a marked inhibitory effect. The other compounds were inactive or only marginally active. In accordance with the in vivo results cDDP was also very active on the MXT+ and MXT- breast cancer cell line. In contrast to this meso-1-PtCl2, meso-1, and DES proved to be only weakly active or inactive on both cell lines. From these results it can be concluded that there is only little if any contribution of the cytotoxic PtCl2 moiety of meso-1-PtCl2 to the anti-breast cancer activity in vivo. On the ER+ MXT-M-3.2 MC transplanted into ovariectomized mice meso-1-PtCl2 yielded a biphasic dose activity curve, i.e. an increase of the tumor growth at low doses followed by a decrease at high doses, identical with those of the estrogens DES and meso-1. These results indicate that meso-1-PtCl2 inhibits ER+ breast cancers by its estrogenicity in the same manner as meso-1 and DES. The complex mechanism of anti-breast cancer active estrogens involves presumably the endocrine and/or the immune system. Its investigation is the subject of further studies.

Animals↗

PubMed1999

[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] sulfatoplatinum(II)--pharmacokinetic studies.

The maximally attainable level of the non-plasma protein bound fraction of a single 10.0 mumol/kg i.p. dose of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] sulfatoplatinum(II), a drug active on the murine, hormone-sensitive MXT-M-3.2 breast cancer, lies markedly below the concentration causing a significant cytotoxic effect on a cell line derived from this tumor. This result confirms our opinion that the strong in vivo activity of this drug on hormone-sensitive breast cancers is mediated by its estrogenic potency by analogy with high dosed steroidal and non-steroidal estrogens. A specific cytotoxic effect utilizing the estrogen receptor as carrier, as formerly postulated, is unlikely.

Animals↗

PubMed1999

Transforming potential of the adenovirus type 5 E4orf3 protein.

Previous observations that the adenovirus type 5 (Ad5) E4orf6 and E4orf3 gene products have redundant effects in viral lytic infection together with the recent findings that E4orf6 possesses transforming potential prompted us to investigate the effect of E4orf3 expression on the transformation of primary rat cells in combination with adenovirus E1 oncogene products. Our results demonstrate for the first time that E4orf3 can cooperate with adenovirus E1A and E1A plus E1B proteins to transform primary baby rat kidney cells, acting synergistically with E4orf6 in the presence of E1B gene products. Transformed rat cells expressing E4orf3 exhibit morphological alterations, higher growth rates and saturation densities, and increased tumorigenicity compared with transformants expressing E1 proteins only. Consistent with previous results for adenovirus-infected cells, the E4orf3 protein is immunologically restricted to discrete nuclear structures known as PML oncogenic domains (PODs) in transformed rat cells. As opposed to E4orf6, the ability of E4orf3 to promote oncogenic cell growth is probably not linked to a modulation of p53 functions and stability. Instead, our results indicate that the transforming activities of E4orf3 are due to combinatorial effects that involve the binding to the adenovirus 55-kDa E1B protein and the colocalization with PODs independent from interactions with the PML gene product. These data fit well with a model in which the reorganization of PODs may trigger a cascade of processes that cause uncontrolled cell proliferation and neoplastic growth. In sum, our results provide strong evidence for the idea that interactions with PODs by viral proteins are linked to oncogenic transformation.

Adenovirus E1A Proteins↗

PubMed1998

Quantitation of hyaluronidases by the Morgan-Elson reaction: comparison of the enzyme activities in the plasma of tumor patients and healthy volunteers.

The Morgan-Elson reaction, a method for the determination of hyaluronidase activity, was optimized for the quantitation of the enzyme in biological material. Based on HPLC and spectrometric (UV-Vis, LC-MS) studies, the structure of the red-colored product (mesomeric forms of N3-protonated 3-acetylimino-2-(4-dimethylaminophenyl)methylidene-5-(1,2-++ +dihydroxyethyl)furane) formed by condensation of chromogen III with p-dimethylaminobenzaldehyde is proposed. Activities corresponding to > or = 0.1 IU of endogenous and therapeutically administered hyaluronidase can be detected in 50 microl samples. Application of the method for the determination of the enzyme in plasma of tumor patients revealed no difference in activity levels, interindividual variability and pH profile compared to healthy volunteers.

Adult↗

PubMed1998

Pharmacokinetics and tissue distribution of bovine testicular hyaluronidase and vinblastine in mice: an attempt to optimize the mode of adjuvant hyaluronidase administration in cancer chemotherapy.

The influence of the route of administration (i.v., i.p. and s.c.) on pharmacokinetics and tissue distribution of bovine testicular hyaluronidase and vinblastine was studied in mice (plasma, skeletal muscle, liver, kidney and human melanoma). After i.v. injection, hyaluronidase was accumulated in liver and kidney, whereas i.p. and s.c. administration led to almost equal distribution in plasma, muscle, liver and kidney. In melanoma, the highest levels of hyaluronidase were found after s.c. injection of the enzyme close to the tumor. Hyaluronidase s.c. increased the intratumoral concentration of s.c. co-administered vinblastine most efficiently, making local simultaneous application as in interstitial chemotherapy most promising.

Animals↗

PubMed1997

The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function.

We have recently shown that the adenovirus type 5 E4orf6 protein interacts with the cellular tumor suppressor protein p53 and blocks p53 transcriptional functions. Here we report that the E4orf6 protein can promote focus formation of primary rodent epithelial cells in cooperation with adenovirus E1A and E1A plus E1B proteins. The E4orf6 protein can also inhibit p53-mediated suppression of E1A plus E1B-19kDa-induced focus formation. Mutant analysis of the E4orf6 protein demonstrates that these activities correlate with the ability of the adenovirus protein to relieve transcriptional repression mediated by the carboxyl-terminal region of p53 in transient transfection assays. We further demonstrate that expression of wild-type E4orf6 correlates with a dramatic reduction of p53 steady-state levels in transformed rat cells. Our data demonstrate that adenovirus type 5 encodes two different proteins, E1B-55kDa and E4orf6, that bind to p53 and contribute to transformation by modulating p53 transcriptional functions.

Adenovirus E1A Proteins↗