Cyclin D1 and retinoblastoma protein expression in Kaposi's sarcoma

Cyclins are implicated in the induction and control of the cell cycle. Cyclin D1 regulates G1-phase progression by phosphorylation of the retinoblastoma protein (pRb). The Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV) contains and transcribes an open reading frame with sequence similarities to cellular D-type cyclins. The KSHV-cyclin protein is associated with kinase activity capable of phosphorylating pRb in vitro. Here, we study for the first time the endogenous cyclin D1 and Rb protein expression in Kaposi's sarcoma (KS) tissue. Twenty-four consecutive biopsies of AIDS-related (n=21) and classical (n=3) KS were studied by immunohistochemistry with monoclonal antibodies against cyclin D1 and pRb. We detected cyclin D1 in 1 of 13 patch/plaque stage, in 4 of 5 nodular stage and in 3 of 6 visceral KS lesions. By Western blot analysis, this cellular cyclin D1 monoclonal antibody did not cross-react with the purified KSHV-cyclin protein. The pRb was consistently detected in 24 of 24 KS lesions. In summary, early KS lesions rarely have detectable expression of endogenous cyclin D1. Advanced and disseminated KS lesions tend to have overexpression of endogenous cyclin D1. Therefore, cellular cyclin D1 expression appears to correlate with tumor progression in KS. The endogenous cyclin D1 is antigenically distinct from the KSHV-cyclin homolog. The pRb, which may serve as a substrate for KSHV-cyclin, is found in all KS lesions examined.     

Differential expression of telomerase activity in human cervical cancer and cervical intraepithelial neoplasia lesions

PURPOSE: Telomeres are tandem arrays of repeated DNA sequences located at the ends of eukaryotic chromosomes, and are synthesized by the enzyme telomerase. Loss of telomeric DNA may play an important role in the development of human cancers. However, very little is known about the status of telomerase during human cervical cancer development. PATIENTS AND METHODS: Telomerase activity was measured by telomere repeat amplification protocol (TRAP) assay in 24 cervical cancers, one carcinoma in situ (CIS), and 20 cervical intraepithelial neoplasia (CIN) lesions. Adjacent nontumor cervical tissue from the same 24 cervical cancer patients and normal cervical tissues from 11 control individuals also were examined for the presence of telomerase activity. RESULTS: Twenty two of the 24 (91.7%) cervical cancer specimens and the single CIS tissue were strongly positive for telomerase activity. Relatively weak but distinctive telomerase activity also was detectable in one of four CIN-I (25%), two of eight CIN-II (25%), and two of eight CIN-III (25%), respectively. However, telomerase activity was not found in the 24 corresponding nontumor cervical tissues from the same cervical cancer patients and the 11 normal cervical tissues from control individuals. CONCLUSION: The majority of cervical cancers contain strong telomerase activity. Significant proportions of noncancerous CIN tissues also contain telomerase activity, although weaker than that in cervical cancer. It seems that there is a progressive increase of telomerase activity in association with an increased degree of cervical malignancy. These results seem to suggest that the expression of telomerase may play a crucial role in cervical cancer carcinogenesis.     

Cyclin D1 gene amplification and p16 gene deletion in patients with esophageal carcinosarcoma

BACKGROUND: Interventional magnetic resonance (MR) imaging allows neurosurgeons to interactively perform surgery using MR guidance. High-field (1.5-Tesla) strength imaging provides exceptional visualization of intracranial and spinal pathology. The full capabilities of this technology for pediatric neurosurgery have not been defined or determined. MATERIALS AND METHODS: From January 1997 through June 1998, 10 of 85 cases performed in the interventional MR unit were in the pediatric population (mean age 8.3, median 8, range 2-15 years). Procedures included 2 brain biopsies, 5 craniotomies for tumor, 2 thoracic laminectomies for syringomyelia, and placement of a reservoir into a cystic brainstem tumor. The biopsies and reservoir placement were performed using MR-compatible equipment. Craniotomies and spinal surgery were performed with conventional instrumentation outside the 5-Gauss magnetic footprint. Interactive and intraoperative imaging was performed to assess the goals of surgery. RESULTS: Both brain biopsies were diagnostic for cerebral infarct and anaplastic astrocytoma and the reservoir was optimally placed within the tumor cyst. Of the 5 tumor resections, all were considered radiographically complete. One biopsy patient and 1 tumor resection patient experienced transient neurological deficits after surgery. The patient with the thoracic syrinx required reoperation when the syringosubarachnoid shunt migrated into the syrinx 3 months after initial placement. No patient sustained a postoperative hemorrhage. Tumor histologies found at craniotomy were craniopharyngioma, ganglioglioma, and 3 low-grade gliomas. No evidence of tumor progression has been seen in any of these patients at a mean follow-up of 5.3 (range 4-8) months. The goals of the procedure were achieved in all 10 cases. There were no untoward events experienced related to MR-compatible instrumentation or intraoperative patient monitoring, despite the present inability to monitor core body temperature. CONCLUSIONS: 1.5-Tesla interventional MR is a safe and effective technology for assisting neurosurgeons to achieve the goals of pediatric neurosurgery. Preliminary results suggest that surgical resection of histologically benign tumors is enhanced in the interventional MR unit. The incidence of surgically related morbidity is low.     

Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.     

Cyclin D1 overexpression in malignant lymphomas

Cyclin D1, the regulatory subunit of certain protein kinases thought to advance the G1 phase of the cell cycle, is now established as a proto-oncogene, with evidence indicating that its derangement may contribute to the uncontrolled cell growth characteristic of tumors. The chromosomal translocation t(11;14)(q13:q32), involving rearrangement of the BCL-1 locus, is closely associated with human lymphoid neoplasia affecting mantle cell lymphomas (MCL). Recently, the putative BCL-1 proto-oncogene turned out to be none other than the cyclin D1 gene. Although the observed break points in the BCL-1 locus are not tightly clustered, its rearrangement has been documented in 40-70% of cases of mantle cell lymphoma, whereas it only rarely occurs in other B cell lymphomas. Of note, all of the known break points leave the cyclin D1 coding region structurally intact and result in increased protein expression, implying that this may provide a highly sensitive and specific marker for MCL. Recent studies demonstrated that immunohistochemical detection in paraffin-embedded material, using a monoclonal antibody, is very useful for routine diagnosis. Current knowledge of cyclin D1 overexpression in malignant lymphomas, with emphasis on its clinicopathologic significance, is reviewed.     

Cyclin D1 overexpression related to retinoblastoma protein expression as a prognostic marker in human oesophageal squamous cell carcinoma

Aspergillus sp. sinusitis is not uncommon in immunocompromised patients but is unusual in patients who are not immunocompromised. The disease may occur as a saprophytic condition, as an allergic sinusitis or as a potentially lethal invasive disease. The differentiation between non-invasive and invasive Aspergillus sp. sinusitis is crucial and this distinction is fully discussed. The treatment options are also considered. Invasive disease requires aggressive treatment with long-term antifungal agents in sufficient doses combined with wide surgical excision. We present a patient who presented with invasive Aspergillus fumigatus sinusitis and subsequently developed cranial neuropathies and skull base osteitis. She was initially treated with oral itraconazole (400 mg daily) for 18 months but due to lack of response this was changed to a new experimental oral azole (voriconazole) which was continued for a further 14 months. She has since remained well for the last five years.     

Cyclin D1 expression as a prognostic parameter in papillary carcinoma of the thyroid

To determine whether ginsenoside-Rd ameliorates the renal injury induced by cephaloridine, the effect of cephaloridine was investigated in rats given ginsenoside-Rd preceding cephaloridine administration and in control rats given no ginsenoside-Rd. In control rats, blood, renal and urinary parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, when ginsenoside-Rd was given orally for 30 consecutive days prior to cephaloridine injection, the activities of the antioxidation enzymes superoxide dismutase and catalase were higher, while malondialdehyde levels in serum and renal tissue were lower in the treated rats than in the controls. The urea nitrogen and creatinine levels in serum were decreased in rats given ginsenoside-Rd. Decreased urine volume, increased urinary osmotic pressure, and decreased urinary levels of glucose, protein, sodium and potassium demonstrated a protective action against the renal dysfunction caused by cephaloridine. In addition, it was demonstrated that ginsenoside-Rd affected cultured proximal tubule cells exposed to cephaloridine.     

Management of cervical neoplasia in human immunodeficiency virus-infected women

The existence of cervical neoplasia in women with human immunodeficiency virus (HIV) represents one of the most serious challenges in the oncologic care of immunosuppressed patients. While the development of most cancers in the immunosuppressed patient can be attributed solely to immune deficiency, the relationship between squamous cell neoplasia of the cervix and HIV is quite unique because of common sexual behavioral risk factors. Screening strategies in HIV-positive women must take into account the high prevalence of cervical dysplasia in this subgroup as well as the limitations of cytologic screening. Cervical dysplasia in HIV-positive women may be of higher grade than in HIV-negative patients, with more extensive involvement of the lower genital tract with HPV-associated lesions. The presence and severity of cervical neoplasia in HIV-positive women correlate with both quantitative and qualitative T-cell function. Standard therapies for preinvasive cervical disease have yielded suboptimal results with high recurrent rates. While poor treatment results of standard ablative and excisional therapies warrant unique therapeutic strategies, one must recognize that close surveillance and repetitive treatment have been successful in preventing progressive neoplasia and invasive cervical carcinoma. The disease characteristics of invasive cervical carcinoma may take a more aggressive clinical course in HIV-infected women. HIV-positive women with cervical cancer have higher recurrence and death rates with shorter intervals to recurrence and death than do HIV-negative control subjects. CD4 status does influence subsequent outcome. In general, the same principles that guide the oncologic management of cervical cancer in immunocompetent patients should be applied. However, extremely close monitoring for both therapeutic efficacy and unusual toxicity must be instituted.     

Cyclin D1 protein expression is related to clinical progression in laryngeal squamous cell carcinomas

The expression of cyclin D1 gene was investigated in 74 laryngeal squamous cell carcinomas (LSCCs) in order to determine its clinical and prognostic value. Overexpression of cyclin D1 was detected immunohistochemically using DCS6 monoclonal antibody on formalin-fixed, paraffin-embedded tissue sections. Cyclin D1 expression was detected in 22 of the 74 cases investigated (30 per cent), thirteen of which presented nodal metastases (59 per cent); of the patients without any detectable cyclin D1 protein expression, six presented nodal metastases (12 per cent). Cyclin D1 protein expression was found in five per cent of the specimens of normal mucosa, eight per cent of those with low-grade dysplasia and 20 per cent of those with high-grade dysplasia. A statistically significant association was found between cyclin D1 expression and the supraglottic site (p < 0.05), tumour extension (p < 0.001), the presence of lymph node metastases (p < 0.001), and advanced clinical stage (p < 0.001). Cyclin D1 expression analysis is an important tool in the selection of LSCC patients with an aggressive clinical course.     

Inactivation of glutathione S-transferase P1 gene by promoter hypermethylation in human neoplasia

Glutathione S-transferases (GSTs) are a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents. The pi-class GST has been associated with preneoplastic and neoplastic changes. Recently, it has been reported that regulatory sequences near the GSTP1 gene, which encodes the human pi-class GST, are commonly hypermethylated in prostatic carcinomas. In the present study, we studied more than 300 primary human tumors originating in other organs for aberrant methylation of GSTP1 using methylation-specific PCR. GSTP1 hypermethylation was most frequent in breast and renal carcinoma, showing aberrant methylation in 30 and 20% of the cases, respectively. Other tumor types showed promoter methylation only rarely or not at all. Hypermethylation of GSTP1 was associated with loss of expression demonstrated by immunohistochemistry. Our results suggest that aberrant methylation of GSTP1 may contribute to the carcinogenetic process in breast and renal carcinomas.     

Cyclin D1和bcl-2在B细胞淋巴瘤中的表达及其在鉴别诊断中的意义

B细胞淋巴瘤根据免疫表型可分为不同亚型,且不同亚型侵袭度不同,预后也有很大差异.Cyclin D1是已被证实与肿瘤有最直接关系的细胞周期蛋白,在大多B细胞淋巴瘤[套细胞淋巴瘤(MCL)、慢性淋巴细胞白血病(CLL)、边缘区淋巴瘤(MZL)、弥漫大B细胞淋巴瘤(DLBCL)等」中均有表达.多数B细胞淋巴瘤[滤泡性淋巴瘤(FL)、DLBCL等]都能可见易位活化的bcl-2表达增强.Cyclin D1及bcl-2作为B细胞淋巴瘤重要的细胞周期蛋白及抗凋亡基因,在淋巴瘤的鉴别诊断中起重要作用,其检测及检测手段的灵敏度和特异度具有重要的临床价值.     

Cyclin D1/PRAD1 as a central target in oncogenesis

Understanding the genetic elements controlling the process of tumor metastasis to distant organ sites such as the liver may be the key to improving survivorship from colon cancer. By using standard cytogenetic techniques in combination with comparative genomic hybridization, multiple genetic imbalances within three human colon cancer cell lines previously selected for differences in liver-metastatic behavior were identified. The entire genome of one poorly metastatic cell line (KM12C) was compared directly with that of two highly metastatic cell lines (KM12SM, KM12L4A) derived from it. A number of chromosomal gains (8q, 12q15, 20q11.2) and losses (5p13, 6p21.3, 18) were common to all three cell lines and are likely related to early tumor development rather than to the selection process used to generate cell lines of increased metastatic potential. Chromosomal imbalances detected only in the highly metastatic cell lines were also observed. KM12SM showed losses of portions of 2p22, 2q24.3--> 2q32.2, 4p15.3--> cen, 4q24 without the 13q and 15q22.3 gains noted for KM12C. Both gains (1p31.3--> 1p21, 2q22--> 2q33, 3cen--> 3q26.2, 5q14--> 5q23, 6cen--> 6q23) and losses (16p, 17p, 17q 19p, 19q 22q) were observed for KM12L4A but not for the other two cell lines. Identification of these alterations provides valuable insight into the process of experimental liver metastasis and is a first step towards mapping genes linked to the terminal phases of human colon cancer progression.     

TFF1 gene expression in human medullary thyroid carcinoma

This epidemiological study investigated the reasons why children in Northern Ireland who need orthodontic treatment do not receive treatment even when it is provided free by the state. A total of 1584 15- and 16-year-olds were examined in 23 high schools with the Index of Orthodontic Treatment Need. The characteristics of the adolescents who had received orthodontic treatment were compared with those who had a definite need for treatment and yet did not receive treatment or advice. One in 10 of the adolescents examined had an unmet need for orthodontic treatment. Logistic regression analysis was used to assess the influence of 11 variables including socioeconomic status, religion, and standard of dental health on the uptake of orthodontic care. This analysis revealed that the only significant predictors of whether an adolescent received orthodontic treatment was the dental attendance pattern of the adolescent, the adolescent's dental health, and the dental attendance pattern of the adolescent's mother. Those adolescents who had good dental health, who regularly attended a dentist, and whose mother regularly attended a dentist were more likely to receive orthodontic treatment.     

Enhanced expression of cyclin D1 in senescent human fibroblasts

When human fibroblast, TIG-1, was growth-stimulated with fetal bovine serum, the induction level of cell cycle-dependent genes was generally much lower in senescent cells than in young counterparts. Exceptionally, the expression level of cyclin D1 in senescent cells was constitutively higher than in young cells and further increased after serum stimulation, which was confirmed by Northern and Western blots and immunoprecipitation. This was also true in other human diploid fibroblast lines, TIG-3 and MRC-5. However, cyclin D1-dependent kinase activity was not detected in senescent cells. When sense- or antisense-cyclin D1 cDNA driven by beta-actin promoter was transfected into young TIG-1 cells, the number of appeared colonies from sense-strand transfected cultures was lower than that from antisense-strand-transfected ones. However, clones expressing cyclin D1 at low or undetectable level which were isolated after transfection with antisense-cyclin D1 proliferated up to the same division limit as untransfected and sense-strand transfected cells. Four clones of SV40-transformed TIG-1 expressed cyclin D1 at moderate levels during their extended proliferative lifespan. It appears that, if the extremely overexpressed cyclin D1 could cause an inhibition of cell proliferation at senescent stage, cellular senescence occurs regardless of overexpression of cyclin D1.     

The roles of the human major histocompatibility complex and human papillomavirus infection in cervical intraepithelial neoplasia and cervical cancer

Germ theory and pure culture methods have provided invaluable information concerning the role of bacteria in diseases resulting from a single organism which bypasses a host's defenses. However, they do not provide sufficient information concerning the synergisms which allow the members of biofilm communities to proliferate more effectively as communities rather than as individuals. The mechanisms of these synergies are potential targets for antimicrobial agents as well as potential mechanisms of resistance to antimicrobial agents. Understanding community-level phenomena in oral biology requires the culture, identification, and classification of functional plaque communities as well as new methods of identifying and quantifying communal relationships. Cultured biofilm communities also provide ideal models of bacterial self-organization in which information related to adaptive strategies arises not only through the recombination of genes within genomes, but also through the recombination of organisms within communities.     

Angiogenesis is associated with vascular endothelial growth factor expression in cervical intraepithelial neoplasia

Squamous cell carcinoma of the cervix (SCC) is preceded by a premalignant condition known as cervical intraepithelial neoplasia (CIN). The majority of cases of CIN regress spontaneously; however, methods are needed to identify those lesions likely to progress. Increased blood vessel density, signifying angiogenesis, is an independent prognostic indicator in a number of cancers, although little is known about its significance in premalignant lesions. The aim of the present study was to determine the relationship between vessel density, expression of the potent angiogenic factor vascular endothelial growth factor (VEGF) and CIN grade. Using immunohistochemistry, mean vessel density (MVD) and VEGF expression were assessed in samples from 54 patients who had undergone cone biopsy for CIN or hysterectomy for SCC and from 16 patients with no cervical pathology. There were significant increases in MVD and VEGF expression from normal cervix through CIN I to CIN III to invasive SCC, but no difference in mean vessel diameter between groups. There was a strong correlation between mean vessel density and VEGF expression, and both were associated with histological grade of CIN. The original MVDs for a small group of patients later presenting with recurrent disease were found to be equal to or greater than the mean for their histological grade. We conclude that the onset of angiogenesis is an early event in premalignant changes of the cervix due, in part, to enhanced expression of VEGF by the abnormal epithelium.     

Isoantigen ABH in cervical intraepithelial neoplasia

The purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. The correlation between the morphologic diagnosis and the results of the RCA test was limited. The percentages of tissues giving positive (+) or positive-negative (+/-) reactions were very similar in intraepithelial neoplsia (59.2%) and normal squamous epithelium (58.4%). The relationship of the RCA test results and behavior of the lesion was not studied.     

Cyclin D1, another molecule of the year?

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.     

In vivo cyclin E expression as a marker for early cervical neoplasia

BACKGROUND: Heat shock has been associated with the acquisition of tolerance to a wide variety of stressful conditions, including ischemia. This is partly mediated by the production of various heat shock proteins (HSP), including HSP70. One novel approach to the reduction of ischemia-reperfusion injury after lung transplantation is the induction of HSP70 by heat pretreatment of the donor. The purpose of this study was to investigate the feasibility of this approach in an animal model of lung transplantation. METHODS: Animals were divided into six main groups, with groups I to III representing transplanted animals: In groups I and II, donor animals were anesthetized and then underwent heat stress 6 and 12 hours before organ harvest, respectively. Control animals underwent general anesthesia but no heat stress. After harvest, left lungs from groups I to III were preserved for 18 hours at 40 degrees C and then implanted into isogeneic recipients, which were killed 24 hours after reperfusion to assess graft function. Group IV and V animals underwent heat stress followed by a recovery period of 6 and 12 hours, respectively. Lungs were collected both at the time of harvest (right lungs) and after 18 hours of cold preservation (left lungs). Group VI served as nontransplanted controls. Groups IV to VI did not undergo lung transplantation. RESULTS: At the time of harvest but before implantation, HSP70 was significantly increased in heat-shocked nontransplanted donor lungs (groups IV and V) compared with group VI controls. After 18 hours of cold preservation, HSP70 levels were higher in group IV compared with group V and group VI controls. At 24 hours after reperfusion, mean arterial oxygenation was significantly higher in group I compared with group II and group III controls (290.25+/-24.5 vs 154.5+/-23.9 and 119.6+/-11.3 mm Hg, respectively; P < .001). Myeloperoxidase activity was improved in group I compared with group III controls (0.048+/-0.018 vs 0.137+/-0.036 deltaOD/mg/min, respectively; P < .05). The wet/dry weight ratio was also improved in group I compared with group III controls (6.2+/-0.3 vs. 7.8+/-0.4, respectively; P < .05). CONCLUSIONS: Heat pretreatment of the donor 6 hours before harvest results in increased synthesis of HSP70, which offers a dramatic protective effect against subsequent ischemia-reperfusion injury in the lung isograft.     

Beta-core fragment of human chorionic gonadotropin in cervical intraepithelial neoplasia (CIN)

The effect of inhalation of paprine dust on the bronchopulmonary tract and antibody-forming function of the spleen was studied experimentally on two lines of mice: CBA and CC57W, differing from each other by haplotype H-2 and antioxidant status of the organisms under study. During comparative histomorphological examination of lungs and bronchi of the experimental animals a more intensive reaction was found in mice of the CBA line, whereas in mice of the CC57W line vascular changes prevailed without any reactions in the bronchioles. Reactions of the spleen to paprine dust in animals of different lines were also different: the quality of antibody-forming cells in the spleen of CBA line mice with comparatively higher antioxidant status increased under experimental conditions, while it decreased in those of the CC57W line. The data obtained showed dependance of the sensitivity of the organism to action of operational dust on individual genetic properties, demonstrating thus the necessity of applying principles of medical genetics in order to prevent effectively the development of occupational diseases in exposed teams of workers.