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Biomedical subjects

L Cheng

Publications and source records attributed to L Cheng.

At least 91 records · Page 5Linked to original sources

Digital optical imaging of green fluorescent proteins for tracking vascular gene expression: feasibility study in rabbit and human cell models.

PURPOSE: To investigate the feasibility of using a sensitive digital optical imaging technique to detect green fluorescent protein (GFP) expressed in rabbit vasculature and human arterial smooth muscle cells. MATERIALS AND METHODS: A GFP plasmid was transfected into human arterial smooth muscle cells to obtain a GFP-smooth muscle cell solution. This solution was imaged in cell phantoms by using a prototype digital optical imaging system. For in vivo validation, a GFP-lentivirus vector was transfected during surgery into the carotid arteries of two rabbits, and GFP-targeted vessels were harvested for digital optical imaging ex vivo. RESULTS: Optical imaging of cell phantoms resulted in a spatial resolution of 25 microm/pixel. Fluorescent signals were detected as diffusely distributed bright spots. At ex vivo optical imaging of arterial tissues, the average fluorescent signal was significantly higher (P <.05) in GFP-targeted tissues (mean +/- SD, 9,357.3 absolute units of density +/- 1,001.3) than in control tissues (5,633.7 absolute units of density +/- 985.2). Both fluorescence microscopic and immunohistochemical findings confirmed these differences between GFP-targeted and control vessels. CONCLUSION: The digital optical imaging system was sensitive to GFPs and may potentially provide an in vivo imaging tool to monitor and track vascular gene transfer and expression in experimental investigations.

Animals↗

Multiple sclerosis: use of light-chain typing to assist diagnosis.

Although the presence of oligoclonal IgG with abnormal kappa/lambda light-chain ratio in multiple sclerosis (MS) has been known for many years, this finding has not been put to diagnostic use in most routine clinical laboratories. In a retrospective study we report differences in the oligoclonal banding patterns between multiple sclerosis and non-MS patients. We had sufficient cerebrospinal fluid (CSF) on 36 from 71 patients with oligoclonal bands for immunofixation for kappa and lambda light chains, and for free kappa and free lambda. Thirteen out of 14 patients with clinically confirmed MS had predominantly IgG (kappa) banding. In contrast, in seven out of eight patients with diagnoses other than MS the IgG was linked to both kappa and lambda light chains in approximately equal proportions. Nine out of 14 patients with probable/possible/suspected MS showed predominantly IgG (kappa) banding; five others in this group had both IgG (kappa) and IgG (lambda) and free lambda light chains. The finding of IgG (kappa) bands in CSF samples with oligoclonal bands supports a diagnosis of MS.

Humans↗

High levels of transgene expression following transduction of long-term NOD/SCID-repopulating human cells with a modified lentiviral vector.

Both oncoretroviral and lentiviral vectors have been shown to transduce CD34(+) human hematopoietic stem cells (HSC) capable of establishing human hematopoiesis in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice that support partially human hematopoiesis. We and others have reported that murine stem cell virus (MSCV)-based oncoretroviral vectors efficiently transduced HSC that had been cultured ex vivo for 4-7 days with cytokines, resulting in transgene expression in lymphoid and myeloid progenies of SCID-engrafting cells 4-8 weeks post-transplantation. Although lentiviral vectors have been demonstrated to transduce HSC under minimal ex vivo culture conditions, concerns exist regarding the level of transgene expression mediated by these vectors. We therefore evaluated a novel hybrid lentiviral vector (GIN-MU3), in which the U3 region of the HIV-1 long terminal repeat was replaced by the MSCV U3 region (MU3). Human cord blood CD34(+) cells were transduced with vesicular stomatitis virus G envelope protein-pseudotyped lentiviruses during a 48-hour culture period. After a total of 4 days in culture, transduced cells were transplanted into NOD/SCID mice to examine gene transfer and expression in engrafting human cells. Fifteen weeks post-transplantation, 37% +/- 12% of engrafted human cells expressed the green fluorescence protein (GFP) gene introduced by the lentiviral vector. High levels of GFP expression were observed in lymphoid, myeloid and erythroid progenies, and in engrafted human cells that retained the CD34(+) phenotype 15 weeks post-transplantation. This study provides evidence that lentiviral vectors transduced both short-term and long-term engrafting human cells, and mediated persistent transgene expression at high levels in multiple lineages of hematopoietic cells.

Animals↗

Reversal of inhibition by the T7 concatemer junction sequence on expression from a downstream T7 promoter.

We have previously reported that placement of the phage T7 concatemer junction (CJ) just upstream of another gene on a plasmid in a T7 system proved to be inhibitory to expression of the downstream gene. We had hypothesized that the inhibition was a result of a readthrough transcript of the CJ element interacting with the translation start region of the downstream gene; also that in the absence of a T7 termination signal, transcription continued around the plasmid multiple times ("rolling circle" transcription), always juxtaposing the inhibitory CJ sequence proximal to the downstream gene mRNA. Two strong predictions were made from this model: 1) that introduction of a spacer sequence between the CJ element and the downstream gene should alleviate the inhibition, and 2) that reintroduction of a T7 transcription terminator should prevent rolling circle transcription, thereby reversing the inhibition by allowing some transcripts to be generated originating from the downstream promoter that did not contain the inhibitory CJ element upstream. We report here that both of these predictions have been fulfilled. However, the reversal of inhibition was only partial in the construct where the T7 terminator was reintroduced, indicating that there remains a residual inhibitory effect of the CJ element on expression of the downstream gene. A possible explanation is that the CJ element, acting as a pause site for transcription, blocks access to the downstream T7 promoter, thereby reducing transcription from that promoter. If this explanation is correct, steric hindrance of transcription starts resulting from an upstream RNA polymerase pause site may represent a previously unrecognized mechanism of transcriptional control.

Bacteriophage T7↗

Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis.

BACKGROUND: -Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are 2 types of intermediate filament protein. Expression of CK7 is seen in the majority of primary urinary bladder carcinomas. CK20 is restricted to superficial and occasional intermediate cells of the normal urothelium of the bladder. Aberrant CK20 expression has been documented in urothelial carcinoma and has proved useful as an ancillary diagnostic aid for urinary bladder tumor. Our hypothesis is that the pattern of CK7 and CK20 expression in metastatic urothelial carcinoma duplicates the expression of the same markers in the primary tumors. Therefore, immunohistochemical staining of metastatic tumors for these 2 markers may be helpful for differential diagnosis in ambiguous metastatic tumor deposits. OBJECTIVE: -To determine the concordance of CK7 and CK20 expression in primary bladder urothelial carcinoma and the matched lymph node metastasis. DESIGN: -We studied 26 patients with lymph node metastases who underwent radical cystectomy and bilateral lymphadenectomy for bladder carcinoma. Immunohistochemical staining for CK7 and CK20 was performed on formalin-fixed paraffin-embedded tissues containing primary cancers and lymph node metastases. RESULTS: -In all cases, there was a concordant expression of CK20 in the primary cancer and its matched lymph node metastasis. Twelve cases (46%) showed positive CK20 immunoreactivity in the primary tumor and its matched lymph node metastases, whereas 14 cases (54%) were negative for CK20 in both the primary tumor and lymph node metastasis. All cases showed positive CK7 immunoreactivity in the primary cancers and matched lymph node metastases. CONCLUSIONS: -CK20 immunoreactivity is reliably observed in metastases from bladder cancer when the primary tumor expresses CK20.

Adult↗

Conserved genetic findings in metastatic bladder cancer: a possible utility of allelic loss of chromosomes 9p21 and 17p13 in diagnosis.

CONTEXT: Molecular analysis of microsatellite alterations of biologically distinct tumor cell subpopulations from the same patient may aid in the determination of tumor origin and further our understanding of the genetic basis of cancer progression. DESIGN: The authors examined the pattern of allelic loss with polymorphic microsatellite markers on chromosome 9p21 (D9S161, D9S171, IFNA), regions of putative tumor suppressor gene p16, and on chromosome 17p13 (TP53), the p53 locus, in matched primary and metastatic bladder cancers from 9 patients. All patients underwent cystectomy for bladder cancer and had regional lymph node metastases at the time of surgery. Genomic DNA was prepared from primary cancers and matched synchronous lymph node metastases using a microdissection method. RESULTS: The overall frequency of allelic loss was 78% in primary cancer and 89% in paired metastatic cancer. The frequency of allelic loss in the primary cancer was 86% with D9S161, 67% with D9S171, 71% with IFNA, and 80% with TP53. The frequency of allelic loss in matched metastatic cancer was 100% with D9S161, 62% with D9S171, 71% with IFNA, and 80% with TP53. An identical pattern of allelic imbalance (allelic loss or retention) at multiple DNA loci was observed in matched primary and metastatic carcinoma in 8 (88%) cases. One case showed allelic loss in the metastasis, but not in the primary cancer. CONCLUSIONS: The pattern of allelic loss at chromosome 9p21 (p16) and 17p13 (p53) was generally maintained during cancer progression to metastasis, and identical allelic loss in primary cancer was conserved in paired metastatic carcinoma. These data suggest that these genetic changes may be useful in establishing a diagnosis and determining tumor origins in difficult cases.

Aged↗

Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer.

The DNA base excision repair pathway is responsible for the repair of cellular alkylation and oxidative DNA damage. A crucial step in the BER pathway involves the cleavage of baseless sites in DNA by an apurinic/apyrimidinic or baseless (AP) endonuclease (Ape1/ref-1), which is a multifunctional enzyme that acts not only as an AP endonuclease but also as a redox-modifying factor for a variety of transcription factors including Fos, Jun, paired box containing genes (PAX), nuclear factor-kappaB, hypoxia-inducible factor alpha (HIF-1alpha), HIF-like factor (HLF), p53, and others. The expression of Ape1/ref-1 in prostate has not been characterized previously. Ape1/ref-1 nuclear immunohistochemistry levels, scored for intensity as 1+, 2+, or 3+, were 91, 3, and 6% in benign hypertrophy (BPH), 0, 42, and 58% in prostatic intraepithelial neoplasia (PIN) and 3, 30, and 67% in prostate cancer, respectively, clearly showing an increase in Ape1/ref-1 nuclear staining in the PIN and cancer compared with BPH. Furthermore, the level of cytoplasmic staining of Ape1/ref-1 in cancer and PIN were elevated (42 and 36%, respectively) compared with BPH (5%). There was no correlation with prostate-specific antigen values or doubling times to Ape1/ref-1 levels. In conclusion, we have demonstrated that Ape1/ref-1 is dramatically elevated in prostate cancer, the level of staining of Ape1/ref-1 increases from low in BPH to intense in PIN and cancer, and there is an increase in the amount of Ape1/ref-1 in the cytoplasm of PIN and cancer compared with BPH. Given these results, we conclude that Ape1/ref-1 may be a diagnostic marker for early prostate cancer and play a role, through its repair, redox, or both functions, in the physiology of the early development of prostate cancer.

Biomarkers, Tumor↗

[The sieving performance of a new polyethersulfone hollow fiber plasma fractionation membrane].

Plasma fractionation membrane is very important in double filtration plasmapheresis. We studied a new polyethersulfone hollow fiber membrane plasma fractionator and evaluated the effect of time, transmembrane pressure (TMP) and mean shear rate on the sieving coefficient (SC) during membrane plasma fractionation. The sieving coefficients of various proteins reached their maximum values at 40 min at the plasma flow rate QI = 30 ml/min and plasma filtrated flow rate QF = 20 ml/min. The QF increased with the increase of TMP, and the point of the intersection of the curve of the QF vs. TMP and the SC vs. TMP was regarded as the ideal condition for plasma fractionation. The plasma filtrated rate PFR = QF/QI = 0.6-0.7. The TMP changed with the change of the mean shear rate, and the mean shear rate had little effect on the SC. The data is of significance to the application of plasma fractionation membrane.

Membranes, Artificial↗

Effect of sea anemone toxin anthopleurin-Q on sodium current in guinea pig ventricular myocytes.

AIM: To investigate the effects of a sea anemone toxin anthopleurin-Q (AP-Q) isolated from Anthopleura xanthogrammica on sodium current (INa) in isolated guinea pig ventricular myocytes. METHODS: Single myocytes were dissociated by enzymatic dissociation method. INa was recorded using whole-cell patch-clamp technique. RESULTS: AP-Q (3 - 300 nmol/L) increased INa in a concentration-dependent manner. The EC50 value for increasing INa was 104 nmol/L (95 % confidence range: 78 - 130 nmol/L). AP-Q 300 nmol/L shifted the I-V curve to the leftward, changed the membrane potential of half maximal activation to more negative potential from (-36.3 +/- 2.3) mV to (-43 +/- 3) mV (n = 6, P < 0.01) and changed the membrane potential of half maximal inactivation to more positive potential from (-75 +/- 6) mV to (-59 +/- 5) mV (n = 6, P < 0.01). AP-Q 300 nmol/L shortened the half-recovery time of INa from (114 +/- 36) ms to (17 +/- 2) ms (n = 6, P < 0.01). The fast inactivation time constant (tauf) of INa was markedly increased by AP-Q 300 nmol/L. CONCLUSION: AP-Q has a stimulating effect on I(Na) with slowing the inactivation course of INa.

Animals↗

Anti-Fas antibody induces apoptosis in cultured human renal interstitial fibroblasts.

OBJECTIVE: To detect if Fas is expressed in human renal interstitial fibroblasts (hRIFs) and apoptosis of hRIFs can be induced by specific anti-Fas antibody. METHODS: hRIFs were cultured from isolated papillae of human kidney, and identified by morphologic examination, assay of antigenic components and culture in D-valine selective medium. Fas expression in normal hRIFs was detected by RT-PCR and immunocytochemistry staining. After hRIFs were incubated with interferon gamma (gamma-IFN 500 U/ml, 1000 U/ml, 1500 U/ml and 2000 U/ml, respectively) for 48 hours, Fas expression was determined by Northern blot, Western blot and flow cytometry. hRIFs pre-stimulated with gamma-IFN (500 U/ml, 48 hours) were incubated with anti-Fas antibody (IgM, 0.5 microgram/ml) for 12 hours. And apoptosis was identified by morphologic examination, DNA ladder assay and flow cytometry. RESULTS: The cultured hRIFs showed a shuttle-like shape and were positively stained by labeled anti-vimentin antibody but negatively stained by anti-epithelial membrane antibody. They could not grow in the D-valine selective medium and died partly in a week. Fas mRNA and protein were expressed in normal hRIFs and markedly upregulated by stimulation with gamma-IFN. Apoptosis in gamma-IFN pre-stimulated hRIFs was induced by anti-Fas antibody, showing cell nuclear shrinkage and condensation in morphologic feature, internucleosomal DNA fragmentation in DNA ladder assay and a pick of hypo-diploid nuclei by flow cytometry. CONCLUSION: Fas is normally expressed in hRIFs and can be markedly upregulated by gamma-IFN. Anti-Fas antibodies can induce apoptosis of hRIFs pre-stimulated with gamma-IFN.

Antibodies, Monoclonal↗

[Microscopic identification of Rhodiola henryi].

OBJECTIVE: To study the microscipic characteristics of the rhizoma, root, stem, leaf and powder of Rhodiola henryi. METHOD: By microscopic observation. RESULTS: The brown substance was always found in the rhizoma and root of Rhodiola henryi. There was a fiber ring in the cambium region of the stem, and some fiber bundles surrounded the pholem. The epidemis cells of the leaf were different in size, and some were very large. Most stomata were anisocytic. The pollen grains were spherical or oblate, with irregularly reticular veins on the outer walls and three germ pore furrows. CONCLUSION: The above-mentioned characteristics provided a basis for the identification of Rhodiola henryi.

Microscopy↗

[Study on susceptibility test of pathogenic fungi from otorhinolaryngology by Etest method].

OBJECTIVE: To study the sensitivity of pathogenic fungi from otorhinolaryngology to 5 antifungal agents of Ketoconazole (KE), Itraconazole(IT), Fluorocytosine(FC), Amphtericin B (AP) and Fluconazole(FL) by Etest method. METHOD: Etest for determine MIC of 14 pathogenic fungi was performed according to the manufacturer's instructions. The Etest strip containing the 5 antifungal drugs were putted on medium with Candida albicans, A. flarus and A. fumigatus etc., respectively, to determine MIC of antifungal drugs. RESULT: Candida albicans were sensitized to all the above 5 antifungal drugs, KE and IT were most sensitized. Seven fungi such as A. flavus, A fumigatus, A. oryzae etc were all sensitized to KE and IT. The MIC range of KE and IT against 15 strains of pathogenic fungi were < or = 0.008-2 mg/L and < or = 0.006-4 mg/L respectively. In 15 strains, 11 strains showed drug-resistant to FL, 8 strains to AP and FC, 4 strains to KE and 1 strains to IT respectively and MIC were all > 32 mg/L. CONCLUSION: Etest MIC were in good agreement with macrobroth MIC. The use of Etest strips for antifungal susceptibility test is a new and promising method with advantage of easy to perform, exact results and satisfactory reproducibility. Etest is valuable on clinical practice.

Antifungal Agents↗

[Studies on the triterpenoidal saponins from flowers of Eriobotrya japonica].

OBJECTIVE: To investigate the chemical composition of the flowers of Eriobotrya japonica. METHODS: Four constituents were isolated from the ethanolic extracts of flowers of Eriobotrya japonica (Thunb) Lindl and were identified by chemical methods and spectroscopic (IR, MS, 1HNMR, 13CNMR). RESULTS: The structures were identified as: Oleanolic acid (I), Ursolic acid(II), 2 alpha, 3 alpha, 19 alpha-Trihydroxyurs-5,12-dien-28-acid (III) and 2 beta, 3 beta, 23 alpha-Trihydroxyolean-12-en-28-acid (IV). CONCLUSION: The compounds I, II, III and IV were obtained from the flowers of Eriobotrya japonica for the first time.

Eriobotrya↗

[Study on anticonvulsive effect of rhizoma pinelliae].

Anticonvulsive effect of water-soluble extract of rhizoma Pinelliae was studied. The result showed that the extract of rhizoma Pinelliae could remarkably inhibit the convulsion induced by strychnine and obviously reduce mortality rate in mice. But the extract could be destroyed easily by heat.

Animals↗

Proximity of prostate cancer to the urethra: implications for minimally invasive ablative therapies.

OBJECTIVES: The delivery of thermotherapy, cryotherapy, and interstitial radiation with minimal morbidity is dependent on the preservation of the prostatic urethra. Our aim was to determine the distribution of the distance between the urethra and the nearest prostate cancer. METHODS: We determined the location of cancer in 350 prostate cancers treated by radical prostatectomy between 1991 and 1993. Each pathologic specimen was totally embedded, serially sectioned, and whole mounted. For each prostate, the radial distance from the urethra to the nearest cancer was determined (urethral-cancer distance). The urethra-cancer distance was correlated with the clinical, pathologic, and laboratory factors. Univariate and multivariate associations with progression-free survival were determined. RESULTS: The mean follow-up was 6.1 years. Ninety-three patients had biochemical, local, or systemic cancer recurrence. The mean +/- SD distance from the urethra to the nearest cancer was 3 +/- 3 mm (range 0 to 18). In 58 patients (17%), the cancer touched the urethra. A decreasing urethra-cancer distance was associated with increasing rates of cancer recurrence (P = 0.009). The urethra-cancer distance correlated with each of the following preoperative factors: preoperative prostate-specific antigen (r = -0. 22, P <0.001), Gleason score in biopsy specimen (r = -0.13, P = 0.02), and percentage of Gleason score 4 or 5 in the biopsy specimen (r = -0.17, P = 0.008). CONCLUSIONS: The distance between the urethra and the nearest cancer was associated with prostate cancer outcome. Many patients have cancer close to the urethra. This finding may have implications for nonsurgical ablative therapies for prostate cancer.

Aged↗

Repair of tobacco carcinogen-induced DNA adducts and lung cancer risk: a molecular epidemiologic study.

BACKGROUND: Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer. METHODS: From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided. RESULTS: Overall, lower DRC was observed in case patients than in control subjects (P:<.001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2.0 with 95% CI = 1.2-3.4, and OR = 4. 3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; P:(trend)<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer. CONCLUSION: The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies.

Age Factors↗

The role of thymus-expressed chemokine and its receptor CCR9 on lymphocytes in the regional specialization of the mucosal immune system.

Chemokines play an important role in the migration of leukocytes at sites of inflammation, and some constitutively expressed chemokines may direct lymphocyte trafficking within lymphoid organs and peripheral tissues. Thymus-expressed chemokine (TECK or Ckbeta-15/CCL25), which signals through the chemokine receptor CCR9, is constitutively expressed in the thymus and small intestine but not colon, and chemoattracts a small fraction of PBLs that coexpress the integrin alpha(4)beta(7). Here we show that TECK is expressed in the human small bowel but not colon by endothelial cells and a subset of cells in intestinal crypts and lamina propria. CCR9 is expressed in the majority of freshly isolated small bowel lamina propria mononuclear cells (LPMC) and at significantly higher levels compared with colonic LPMC or PBL. TECK was selectively chemotactic for small bowel but not colonic LPMC in vitro. The TECK-induced chemotaxis was sensitive to pertussis toxin and partially inhibited by Abs to CCR9. TECK attracts predominantly the T cell fraction of small bowel LPMC, whereas sorted CD3(+)CCR9(+) and CD3(+)CCR9(-) lymphocytes produce similar Th1 or Th2 cytokines at the single cell level. Collectively, our data suggest that the selective expression of TECK in the small bowel underlie the homing of CCR9(+) intestinal memory T cells to the small bowel rather than to the colon. This regional specialization implies a segregation of small intestinal from colonic immune responses.

Cell Movement↗

Cdk2-dependent phosphorylation and functional inactivation of the pRB-related p130 protein in pRB(-), p16INK4A(+) tumor cells.

The retinoblastoma family proteins pRB, p107, and p130 are phosphorylated and released from E2Fs in the late G(1) phase of the cell cycle. This phosphorylation is thought to contribute to the derepression of E2F-responsive genes and to be mediated, in part, by Cdk4 and Cdk6. Evidence that Cdk4/6 activity is inhibited by p16(INK4A) in most pRB(-) cells suggests that p107 and p130 may be underphosphorylated and remain associated with E2Fs during G(1)-S progression in cells that lack pRB. To examine this, we evaluated the cell cycle-dependent phosphorylation and E2F binding abilities of p107 and p130 in pRB(-), p16(+) Saos-2 osteosarcoma cells. p130, but not p107, was phosphorylated and released from E2F-4 in late G(1) and S phase cells, although p130 phosphorylation differed qualitatively in these and other pRB(-), p16(+) cells as compared with pRB(+), p16(-) cell types. p130 phosphorylation occurred in the absence of cyclin D-Cdk4/6 complexes, coincided with cyclin E- and Cdk2-associated kinase activity, and was prevented by expression of dominant negative Cdk2. Moreover, dominant negative Cdk2 prevented the dissociation of endogenous p130-E2F-4 complexes and inhibited E2F-4-dependent transcription. These findings show that p130 can be phosphorylated and functionally inactivated in a Cdk2-dependent process, and they highlight the involvement of distinct Cdks in the regulation of different pRB family proteins.

CDC2-CDC28 Kinases↗