Search PubMed⌕ Search

Biomedical subjects

V Levin

Publications and source records attributed to V Levin.

At least 19 recordsLinked to original sources
PubMed2006

Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells.

Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

Active Transport, Cell Nucleus↗
PubMed2000

Observation of ultrasound velocity gradient in fullerene ceramics by acoustic microscopy

A scanning acoustic microscope is used to study the distribution of elastic properties in small samples (O 3 x 2 mm3) of new hard phases of C60. The specimens under investigation were synthesized from pure C60 powder under pressure P = 8 GPa in the temperature range 500-1650 K. The time-of-flight mode was used for bulk sound wave velocity determination in a direction parallel to the cylinder's axis. Longitudinal sound wave velocities greater than 10,000 m/s were found for all specimens treated at temperatures higher than 1000 K. Using the B-scan mode allowed us to observe the velocity gradient in the sample's periphery. The heterogeneous internal structure of the specimen is visualized in the images formed in C- and B-scan modes.

Journal Article↗
PubMed2000

The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma cells.

Medulloblastoma is the most malignant pediatric brain tumor. It is believed to originate from the undifferentiated external granule layer cells in the cerebellum, but the mechanism of tumorigenesis remains unknown. Here we studied three types of human medulloblastoma cells that express markers corresponding to different levels of neuronal differentiation. They expressed the neuronal repressor element 1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF; refs. 7-10) at very high levels compared with either neuronal progenitor NTera2 (NT2) cells or fully differentiated human neuron teratocarcinoma (hNT cells). To counter the effect of REST/NRSF, we used a recombinant transcription factor, REST-VP16, constructed by replacing repressor domains of REST/NRSF with the activation domain of viral protein (VP16). Transient expression of REST-VP16 in medulloblastoma cells was able to compete with the endogenous REST/NRSF for DNA binding and stimulate neuronal promoters. High-efficiency expression of REST-VP16 mediated by adenovirus vectors (Ad.REST-VP16) in medulloblastoma cells was able to counter REST/NRSF-mediated repression of neuronal promoters, stimulate expression of endogenous neuronal genes and trigger apoptosis through the activation of caspase cascades. Furthermore, intratumoral injection of Ad.REST-VP16 in established medulloblastoma tumors in nude mice inhibited their growth. Therefore, REST/NRSF may serve as a new target for therapeutic interventions for medulloblastoma through agents such as REST-VP16.

Adenoviridae↗
PubMed2000

Biology and treatment of malignant glioma.

Malignant gliomas are a heterogeneous group of tumors that are associated with significant morbidity and mortality. The development of the malignant phenotype is the result of a complex series of events that influence gene expression, angiogenesis, and invasion and favor the growth of tumor cells. Currently, the management of malignant glioma consists of symptom control and cytoreduction with a combination of surgery, radiation therapy, and chemotherapy. However, there is no satisfactory regimen available for adjuvant or salvage chemotherapy for these neoplasms. An overview of the biologic mechanisms, grading systems, and treatment options for anaplastic astrocytoma and glioblastoma multiforme is presented.

Astrocytoma↗
PubMed1999

Attenuation of WAF1/Cip1 expression by an antisense adenovirus expression vector sensitizes glioblastoma cells to apoptosis induced by chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.

Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression renders glioma cells resistant to chemotherapy agents. In this study, we investigated whether down-regulation of WAF1/Cip1 would sensitize gliomas to chemotherapy. An adenoviral vector expressing antisense WAF1/Cip1 was constructed and used to infect D54 glioma cells, which express a high level of endogenous WAF1/Cip1. After D54 cells were infected with antisense WAF1/Cip1 adenovirus, Western blotting revealed a significant decrease in the WAF1/Cip1 protein level. Down-regulation of WAF1/Cip1 alone resulted in the cells rounding up and detaching from plates. Electron microscopy revealed some nuclear fragmentation in antisense WAF1/Cip1-infected cells, indicating the initiation of apoptosis. The antisense WAF1/Cip1-infected cells were then treated with the chemotherapeutic agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Other cells were infected with sense WAF1/Cip1 adenovirus or control virus and served as controls. Trypan blue exclusion assay revealed significant cell death in antisense WAF1/Cip1-infected cells. In situ end-labeling assay by flow cytometry revealed that many cells died of apoptosis. Our results show that the attenuation of WAF1/Cip1 expression initiated glioma cell death and sensitized glioma cells to apoptosis induced by 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin. Thus, blocking WAF1/Cip1 production may serve as a useful chemosensitization regimen for treating glioma.

Adenoviridae↗
PubMed1998

Overexpressed WAF1/Cip1 renders glioblastoma cells resistant to chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.

Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression may be a factor in cancer chemoresistance. We established a doxycycline-inducible WAF1/Cip1 expression system in two glioblastoma cell lines and examined the role of WAF1/Cip1 in their response to the chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis-diamminedichloroplatinum (cisplatin), in an isogeneic background. Our results showed that the induction of WAF1/Cip1 expression rendered glioma cells resistant to cell death induced by BCNU and cisplatin. Using an in vivo host-cell reactivation DNA repair assay, we demonstrated that WAF1/Cip1 enhances the repair of BCNU-induced DNA damage. We conclude that WAF1/Cip1 allows repair of BCNU- and cisplatin-damaged DNA and protects glioma cells from chemotherapy agent-induced apoptosis. Thus, blocking WAF1/Cip1 production or function may serve as a useful chemosensitization regimen for glioma.

Antineoplastic Agents↗
PubMed1998

Detection of p21WAF1/Cip1 in brain metastases.

The p21WAF1/Cip1 (p21) protein, a negative regulator of G1 checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastases and in corresponding primary tumors, we used immunohistochemical staining to examine the expression of p21 in paraffin-embedded sections prepared from primary colon and breast carcinomas and from metastatic brain tumors that originated from colon, breast, lung, and kidney cancers and from melanoma. Our results showed that 56% (28 of 50) of the brain metastases samples have more than 1% p21-positive staining cells compared with 87% of primary gliomas reported previously. Among the samples analyzed, p21 expression in brain metastases from breast carcinomas was much higher than in primary breast carcinomas. In contrast, p21 expression in brain metastases from colon carcinomas was less than primary colon carcinomas. The results from this pilot study suggest that p21 expression is regulated differently in metastatic and primary tumors.

Brain Neoplasms↗
PubMed1997

Association between human immunodeficiency virus type 1 infection and cancer in the black population of Johannesburg and Soweto, South Africa.

A case-control study of 913 black cancer patients (aged 15-50 years) was undertaken to measure the association between human immunodeficiency (HIV) infection and cancers believed to have an infective aetiology. Controls were patients with cancers believed not to be infective in origin. The prevalence of HIV in the controls of 7.3% (24 of 325) was similar to the background HIV seropositivity in this population. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status and sex were calculated. There was a strong association between HIV infection and Kaposi's sarcoma (KS), with 27 of 33 cases being HIV seropositive, OR = 61.8 (95% CI 19.7-194.2) and an elevated association with non-Hodgkin's lymphoma (NHL), with 27 of 40 cases being HIV seropositive [OR = 4.8 (95% CI 1.5-14.8)]. The elevated odds ratio for KS associated with HIV infection accords with the observed increases in the incidence of KS in several sub-Saharan African countries where the prevalence of HIV is high. The odds ratio for NHL associated with HIV infection was lower than that reported in developed countries, and the reason for this is not clear. No other cancers, including cervical and liver cancers, showed significantly elevated odds ratios associated with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Adenoid cystic carcinoma of the salivary glands: a review of 10 years.

A retrospective analysis was performed of 50 patients with adenoid cystic carcinoma who were seen in the Department of Radiation Oncology, University of Witwatersrand, Johannesburg, South Africa, in the past 10 years. There were 25 men and 25 women with a mean age of 52 years (age range, 21 to 88 years). Five patients had metastatic disease, and 17 had neural invasion. Thirty-four patients had surgery (11, complete; 23, microscopic residual). Sixteen patients had radiotherapy as initial management. The disease-free survival was 26%, overall survival was 29%, and local control was 30% at 10 years. Most recurrences occurred in the first 3 years. Nine patients had metastasis following treatment. The mean survival after metastasis was 15 months. Seven prognostic variables were analyzed using the log-rank test. There was no impact of age, site, type of salivary gland (major vs. minor), tumor stage, node positivity, or neural invasion on disease-free survival, overall survival, or local control. Extent of surgical resection (complete vs. microscopic residual) had a significant impact on disease-free survival and local control (P < 0.05) but no impact on overall survival (P > 0.05) because of the slow-growing nature of these tumors. Similarly, patients who had microscopic residual after surgery and were treated with radiotherapy did better than those who had biopsy and radiotherapy, although this was not significant statistically (P > 0.05). Thus, whenever possible, every attempt must be made to remove all microscopic tumor by surgery. Addition of postoperative radiotherapy with high-energy photons did not improve the locoregional control or survival in our series. There is a place for neutrons in the treatment of adenoid cystic carcinomas in advanced cases of inoperable or recurrent tumors, as a review of literature shows.

Adult↗
PubMed1997

The treatment of recurrent unresectable and malignant meningiomas with interferon alpha-2B.

OBJECTIVE: Recurrent malignant meningiomas and unresectable meningiomas represent a great therapeutic challenge after the failure of radiation therapy. No effective chemotherapy has been found. We report the preliminary results of the treatment of patients with recurrent unresectable or malignant meningiomas with recombinant interferon alpha-2B (IFN-alpha-2B). METHOD: Each of six patients with either a recurrent malignant meningioma or an unresectable meningioma was treated with IFN-alpha, administered subcutaneously at a dosage of 4 mU/m2 per day, 5 days per week. Two of the six meningiomas were regular, one was atypical, and three were malignant. RESULTS: Five of six patients exhibited positive response to treatment; with stabilization of the size of the tumor in four patients and slight regression in one. The responses observed lasted from 6 to 14 months. The toxicity associated with prolonged use of IFN-alpha was mild and well tolerated. CONCLUSION: These results suggest that IFN-alpha is effective in the treatment of recurrent malignant meningiomas.

Adult↗
PubMed1996

Morphologic alterations in esophageal squamous cell carcinoma after preoperative high dose rate intraluminal brachytherapy.

BACKGROUND: Total esophagectomy specimens from 4 patients given preoperative high dose rate intraluminal brachytherapy (HDRILBT) of 20 Gray (GY) in 2 fractions of 10 Gy each week were reviewed for radiation changes. METHODS: In all patients, preoperative biopsy specimens showed moderate to poorly differentiated squamous cell carcinoma with minimal to negligible keratin production. The esophagectomy specimens were sampled at the resection margins, the edge of irradiated length, 1 cm from the proximal and distal edge of visible tumor, the center of the tumor, and the lymph nodes. RESULTS: Radiation change in the form of fibrosis was limited to the submucosa at the resection margins, the circular muscle layer at the edge of irradiated length, and full thickness at 1 cm from the edge of the visible tumor and the center of the tumor. Surface epithelium did not show any changes at the resection margins but did show basal cell hyperplasia at the edge of the irradiated length and ulceration at 1 cm from the edge of the visible tumor and the center of the tumor. Endarteritis obliterans was seen only 1 cm from the edge of the visible tumor and the center of the tumor. Necrosis, intense keratin formation, and giant cell reaction were observed at the center of the tumor. When compared with the preradiotherapy biopsies, the amount of keratin in the postradiotherapy specimens was extensive. HDRILBT may cause induction of the keratin gene in the irradiated cells to stimulate differentiation toward better differentiated cells. CONCLUSIONS: HDRILBT may cause the keratin gene in the irradiated cells to induce differentiation toward better differentiated cells. Preoperative high dose rate intraluminal brachytherapy may have a role in improving the prognosis of patients with early esophageal cancer treated with a combination of radiotherapy and surgery.

Adult↗
PubMed1996

Toxicity in patients with testicular seminoma treated with radiotherapy. Different dose levels and treatment fields.

The aim of this study was to evaluate the acute and late effects of irradiation in 56 patients with stage I and II testicular seminomas. A retrospective study of patients' records was performed paying attention to the acute and late toxicity of radiation in relation to treatment fields and radiation doses. Treatment groups were compared using the chi squared-test. Mild to moderate nausea and/or vomiting was seen in 66% of patients and occurred equally independent of the treatment volume or radiation dose. Increased bowel frequency was seen in 59% and was more common when a larger treatment volume was used. Skin reactions increased with increase in treatment volume and dose (p = 0.046). Severe late complications were recorded in two patients (myocardial damage-1/4 at risk, duodenal ulcer-1/56 at risk). These could not be attributed solely to the irradiation as other contributing factors might play a role. Overall the data suggest that the risk of major posttreatment morbidity is minimal for patients with testicular seminoma treated with postoperative radiotherapy.

Acute Disease↗
PubMed1995

Initial experience with telebrachytherapy treatment in palliation of advanced oesophageal cancer.

Ten patients with advanced metastatic squamous cell carcinoma of the middle third of the oesophagus were treated with palliative external radiotherapy and intraluminal brachytherapy. All patients had long lesions, 8-15 cm in length, and narrow lumens that did not allow the passage of a guidewire for dilatation. Improvement in dysphagia by more than 2 grades was seen in 9 of 10 patients. This finding was correlated with an increase in the size of the oesophageal lumen at the end of 6 weeks following treatment by barium swallow. No complications of treatment were noted in any patient. Low doses of external beam radiotherapy and high-dose-rate intraluminal brachytherapy can provide quick and effective palliation in advanced metastatic oesophageal carcinoma.

Adult↗