Biomedical subjects

H Hibshoosh

Publications and source records attributed to H Hibshoosh.

34 records · Page 2Linked to original sources

PubMed1997

Deregulated expression of p27(Kip1) in human breast cancers.

Protein complexes composed of cyclins and cyclin-dependent kinases control the orderly progression of mammalian cells through the cell cycle. The p27(Kip1) protein belongs to a family of cyclin-dependent kinase-inhibitory proteins that are negative regulators of cell cycle progression and have been proposed as candidate tumor suppressor genes. However, the p27(Kip1) gene is only rarely mutated in human primary breast carcinomas and breast cancer cell lines. To further address the role of p27(Kip1) in the development of human tumors, we determined by Western blot analysis the levels of expression of the p27(Kip1) protein in a series of human cancer cell lines and found that this protein is expressed at high levels in many of these cell lines, even during exponential growth. The levels of p27(Kip1) were significantly associated with the levels of cyclins D1 and E. In contrast to the high level of p27(Kip1) in breast cancer cell lines, three cell lines established from normal mammary epithelium expressed low levels of this protein. Cell synchronization studies demonstrated deregulation of the expression of p27(Kip1) throughout the cell cycle in two breast cancer cell lines but normal regulation in a normal mammary epithelial cell line. Immunohistochemical studies on p27(Kip1) expression in 52 primary human breast cancers indicated that this protein was also expressed at relatively high levels in 44% of the tumor samples, but it was barely detectable or undetectable in the remaining 56% of the samples. Additional studies are required to determine why some breast cancer cells express relatively high levels of p27(Kip1) despite its known role as an inhibitor of cell cycle progression.

Biomarkers, Tumor↗

PubMed1996

The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene.

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.

Aged↗

PubMed1996

An enormous testicular sex cord/gonadal stromal tumor.

Testicular sex cord/gonadal stromal tumors are relatively rare non-germ cell neoplasms. The authors describe an unusual case of an enormous unclassified sex cord/gonadal stromal tumor, which histologically appeared benign. The implications of the pathological findings and the surgical management are discussed.

Adolescent↗

PubMed1996

Giant multilocular cystadenoma of the prostate.

Giant multilocular prostatic cystadenoma is a rare clinicopathologic entity characterized by benign histology and the ability to enlarge massively. The lesion may arise from the prostate gland either in continuity with the prostatic urethra or separate from it, or it may arise as a lesion distinct from the prostate gland. Obstructive voiding symptoms occur in all reported cases. The use of preoperative radiographic evaluation, such as magnetic resonance imaging, effectively defines the lesion's benign nature and aids in planning surgical extirpation.

Aged↗

PubMed1996

Increased expression of cyclin D1 is an early event in multistage colorectal carcinogenesis.

BACKGROUND & AIMS: Cyclin D1 gene amplification and/or overexpression occurs in several human cancers. The level of expression of cyclin D1 protein during the multistage process of human colon carcinogenesis was determined. METHODS: Cyclin D1 protein abundance was determined by immunostaining samples of normal colonic mucosa(n=23), transitional normal mucosa adjacent to adenomas or adenocarcinomas (n=41), hyperplastic polyps (n=8), adenomatous polyps (=35), and adenocarcinomas (n=27), using a polyclonal anti-human cyclin D1 antibody. RESULTS: Cyclin D1 nuclear staining occurred in 30% of adenocarcinomas and 34% of adenomatous polyps but not in hyperplastic polyps or normal or transitional mucosa. Nuclear staining did not correlate with sex, age, size, or dysplasia of the adenomatous polyps or with differentiation and Dukes' staging of the adenocarcinomas. Left-sided colon neoplasms showed nuclear staining more frequently than those right-sided lesions. Diffuse or supranuclear cytoplasmic staining occurred in about one third of hyperplastic polyps, adenomas, and adenocarcinomas and in transitional mucosa adjacent to adenocarcinoma. CONCLUSIONS: Increased nuclear expression of cyclin D1 occurs in around one third of colonic tumors as an early event during multistage process of colon carcinogenesis. Increased expression of cyclin D1 may perturb cell-cycle control in benign adenomas and thereby enhance tumor progression.

Adenocarcinoma↗

PubMed1996

Benign adenomatous kidney neoplasms in children with polycythemia: imaging findings.

PURPOSE: To correlate pathologic, computed tomographic (CT), and ultrasound (US) characteristics of nephrogenic adenofibromas and embryonal adenomas (uncommon pediatric renal tumors) in children. MATERIALS AND METHODS: Medical records and imaging and pathologic findings were reviewed in three children (aged 6 1/2, 7, and 11 years) with adenomatous renal tumors and polycythemia. Specimens were reviewed at the National Wilms Tumor Study Pathology Center (Loma Linda, Calif). RESULTS: All tumors were smaller than 3 cm in greatest dimension. They were hyperechoic on US scans and had high attenuation on unenhanced CT scans. Two patients underwent nephrectomy for initial diagnosis of Wilms tumor. The third underwent local excision. At pathologic examination, embryonal-appearing adenomatous epithelial cells were found to form tubules and papillae with abundant psammomatous calcifications. Two masses were classified as embryonal adenomas and one as nephrogenic adenofibroma. CONCLUSION: Increased attenuation on CT scans and increased echogenicity on US scans of renal adenomatous tumors are distinctive findings that may reflect the presence of tubulopapillary structures and psammomatous calcifications.

Adenofibroma↗

PubMed1996

Response of small cell carcinoma of pancreas to a small cell lung cancer regimen: a case report.

Small cell carcinoma of the pancreas is a very rare malignancy with 18 cases reported in the literature, of which only 3 were treated with chemotherapy. A 52-year-old man was diagnosed with small cell carcinoma originating in the head of the pancreas and invading the duodenum. He was treated with a similar approach as for localized small cell lung cancer, with six cycles of combination chemotherapy and local radiotherapy, and went into complete remission. After 3 months, he developed liver metastases along with an enlarged left supraclavicular lymph node. He was treated with two cycles of CVA, but developed lung metastases and was treated with ifosfamide/mesna. However, his overall condition deteriorated and hospice care was instituted until the patient's demise. The patient survived 14 months following diagnosis, significantly longer than the 15 reported patients with small cell pancreatic carcinomas not treated with chemotherapy. Combination chemotherapy and radiation therapy as it is utilized for small cell lung cancer appear to be beneficial for small cell carcinoma of the pancreas.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Increased expression of the cyclin D1 gene in Barrett's esophagus.

Previous studies have found a 3-10-fold amplification and overexpression of the cyclin D1 gene in about 32% of human esophageal squamous cell carcinoma. The purpose of this study was to evaluate the prevalence of increased expression of the cyclin D1 protein in Barrett's esophagus. Using 69 formalin-fixed and paraffin-embedded human esophageal specimens, which had been removed endoscopically or obtained at surgery during 1993 and 1994, all immunohistochemical analyses were performed using an avidin-biotin complex immunoperoxidase technique. Increased nuclear expression of the cyclin D1 protein was noted in 32 of 69 samples (46%; 44% of the samples from males and 50% of the samples from females). Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women. Nuclear accumulation of the cyclin D1 protein was also found in both dysplastic and nondysplastic lesions, and it was not associated with sex, age, or cigarette or alcohol consumption. Samples from patients taking proton pump inhibitors tended to be less frequently positive (32%) for cyclin D1 nuclear staining when compared to patients taking H2 antagonists (45%) or antacids (55%). These studies suggest that increased expression of cyclin D1 is an early event in the tumorigenic process of esophageal adenocarcinomas and that the increased expression of this gene might predispose the epithelium to malignant transformation.

Adenocarcinoma↗

PubMed1996

Treatment for breast cancer and blood levels of chlorinated hydrocarbons.

Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure.

Aged↗

PubMed1995

Renal hemangiopericytoma. Case report and review of the literature.

Hemangiopericytoma (HPC) is an uncommon tumor which was first described in 1942. There are no unique radiological or clinical identifiers that can reliably aid in preoperative diagnosis. Surgery is the only reliable therapy as both chemotherapy and radiotherapy have proven ineffective in several series. The outcome is difficult to predict; the only reliable predictor is the presence or absence of metastasis. We report on a 63-year-old female with a large left renal HPC.

Female↗

PubMed1992

Isolation and characterization of a highly malignant variant of the SW480 human colon cancer cell line.

We found that the human colon cancer cell line SW480 consists of two distinct subpopulations which we have designated E-type (epithelial) and R-type (round). Pure cultures of each type were obtained by subcloning, and both have maintained their characteristic phenotypes for at least 1 year (40 passages). E-type cells are the major (> 98%) type in the parental SW480 cell line. They form flat epithelial-like colonies. In contrast, R-type cells, which constitute a minor fraction (< 2%) of the parental cell line, have a rounded shape and grow in clusters of piled-up cells. Compared to E-type cells or the parental SW480 cells, isolated R-type cells display decreased doubling time, loss of contact inhibition, less adhesiveness to culture plates, higher anchorage-independent growth in soft agar, and a much more aneuploid karyotype. When injected s.c. into nude mice, R-type cells produce much larger tumors within the same period of time than E-type cells, and the tumors are less differentiated than those produced by the E-type cells. Cell fusion experiments between R-type and E-type cells revealed that the R-type phenotype is dominant, and the results suggest that this is due to one or a few genetic changes. Taken together, these findings suggest that the R-type cells represent a more malignant variant of the E-type cells. They may be useful, therefore, for studying mechanisms involved in tumor progression.

Animals↗

PubMed1991

Effects of overexpression of ornithine decarboxylase (ODC) on growth control and oncogene-induced cell transformation.

The enzyme ornithine decarboxylase (ODC) has been implicated in the control of cell growth, differentiation and tumor promotion. To further elucidate its precise role a murine ODC cDNA was inserted into the retrovirus-derived vector pMV7 and retrovirus-like particles were used to infect NIH3T3 and rat 6(R6) fibroblasts. Derivatives were obtained that stably express a 5-40 fold increase in ODC enzyme activity. Despite these high levels of enzyme activity the cells retained a normal morphology and displayed no major changes in growth properties in monolayer culture or in agar suspension. On the other hand, R6 cells that expressed high levels of ODC displayed a marked increase in susceptibility to morphologic transformation by an activated c-H-ras oncogene. These results provide the first evidence that ODC can cooperate with an activated oncogene in the process of cell transformation. Although the mechanism is not known, these findings may be relevant to the multistage carcinogenic process.

Animals↗

PubMed1984

Mechanisms of reaction of benzo(a)pyrene-7,8-diol-9,10-epoxide with DNA in aqueous solutions.

The physical and chemical reaction pathways of the metabolite model compound benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) in aqueous (double-stranded) DNA solutions was investigated as a function of temperature (0-30 degrees C), pH (7.0-9.5), sodium chloride concentration (0-1.5M) and DNA concentration in order to clarify the relationships between the multiple reaction mechanisms of this diol epoxide in the presence of nucleic acids. The reaction pathways are (1) noncovalent intercalative complex formation with DNA, characterized by the equilibrium constant K, and Xb the fraction of molecules physically bound; (2) accelerated hydrolysis of BPDE bound to DNA; (3) covalent binding to DNA; and (4) hydrolysis of free BPDE(kh). The DNA-induced hydrolysis of BPDE to tetraols and the covalent binding to DNA are parallel pseudo-first-order reactions. Following the rapid (millisecond time scale) noncovalent complex formation between BPDE and DNA, a much slower (approximately minutes) H+-dependent (either specific or general acid catalysis) formation of a DNA-bound triol carbonium ion (rate constant k3) occurs. At pH 7.0 the activation energy of k3 is 8.7 +/- 0.9 kcal/mol, which is lower than the activation energy of hydrolysis of free BPDE in buffer solution (14.2 +/- 0.7 kcal/mol), and which thus partially accounts for the acceleration of hydrolysis of BPDE upon complexation with DNA. The formation of the triol carbonium ion is followed by a rapid reaction with either water to form tetraols (rate constant kT), or covalent binding to DNA (kc). The fraction of BPDE molecules which undergo covalent binding is fcov approximately equal to kc/(kc + kT) = 0.10 and is independent of the overall BPDE reaction rate constant k = kh(1 - Xb) + k3Xb if Xb----1.0, or is independent of Xb as long as k3Xb much greater than kh(1 - Xb). Thus, at Xb = 0.9, fcov is independent of pH (7.0-9.5) even though k exhibits a 70-fold variation in this pH range and k----kh above pH 9 (k3 = kh). Similarly, fcov is independent of temperature (0-30 degrees C), while k varies by a factor of approx. 3. In the range of 0-1.5 M NaCl, fcov decreases from 0.10 to 0.04. These variations are attributed to a combination of salt-induced variations in the factors k3, Xb and the ratio kc/kT.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMedDate not supplied

HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications.

Uterine papillary serous carcinoma (UPSC) is a highly aggressive variant of endometrial cancer with features similar to high-grade ovarian cancer. Patients tend to be elderly, thin, have a high grade tumor with extensive extrauterine disease at the time of diagnosis. The transmembrane receptor encoded by the HER-2 cellular oncogene is amplified in several types of human carcinomas and provides an attractive therapeutic target. HER-2/neu, the transmembrane receptor encoded by the c-erbB2 gene, is overexpressed by immunohistochemistry in <25% of ovarian cancers and 20-30% of breast cancers, and <10% of endometrial cancer. There are prognostic and therapeutic implications associated with the overexpression of this transmembrane protein. Herceptin, a humanized murine monoclonal antibody directed against the extracellular domain of the HER-2/neu protein, is being used to treat breast cancer that overexpresses HER-2/neu. We reviewed all patients diagnosed with UPSC between 1999-2001. Twenty-six patients were identified, and 19 patients had specimens available for evaluation. We performed immunohistochemical analysis (Herceptest, Dako, Carpinteria, CA) on 19 paraffin embedded blocks of UPSC tumors looking for HER-2/neu over expression. Five out of 19 (26%) stained heavily (3+) for HER-2/neu receptor protein. Four of these five patients had advanced disease at diagnosis. Two of these patients were subsequently treated with Herceptin; one with complete response and one with stable disease based on CT scan and CA-125 findings. Targeting HER-2/neu may be beneficial for a select group of patients with UPSC. We are continuing to evaluate samples for HER-2/neu over expression by fluorescence in situ hybridization (FISH).

Antibodies, Monoclonal↗

PubMedDate not supplied

Cyclin D1 overexpression is more prevalent in non-Caucasian breast cancer.

African-American women with breast cancer consistently show a shortened survival when compared with Caucasians with breast cancer, however it is not clear whether this is due to socioeconomic factors or to racial differences in tumor biology. Cyclin D1 overexpression has been demonstrated in 60-80% of female breast cancers, however these studies have not included race or ethnicity data. We examined the level of cyclin D1 protein expression in 139 cases of female breast cancer obtained from different ethnic populations. Using an immunoperoxidase-based technique and a polyclonal anti-cyclin D1 antibody, the rate of overexpression was 68%. Cyclin D1 overexpression tended to be more frequent in cases from non-Caucasian patients when compared with those from Caucasian patients (77% vs. 59%, p=0.051). Our findings suggest that non-Caucasian ethnicity may be important in predicting cyclin D1 overexpression. Cyclin D1 could therefore serve as a possible target in managing breast cancer in the African-American population.

Black People↗

PubMedDate not supplied

Primary melanocytomas of the spinal cord: a report of seven cases.

Seven cases of primary intramedullary melanocytomas of the spinal cord are reported with clinical features, light microscopy, immunohistochemistry, and ploidy analysis. The patients ranged in age from 24 to 74 years. The tumors were composed predominately of spindle cells with focal aggregates of epithelioid cells. The nuclei were round to oval with variably prominent nucleoli. The tumors contained variable amounts of melanin pigment. Immunohistochemical staining with HMB 45 was positive in 5 cases and negative in 2. None of the tumors was immunoreactive for epithelial membrane antigen (EMA). The clinical outcome ranged from death at 9 days following surgery to 4-year survival without recurrence. The tumors were compared with 5 metastatic melanomas and were found to have a markedly different histology, S phase fractions, and proliferation indices. The categorization of the primary pigmented lesions of the CNS is further discussed in the context of dermatopathologic nomenclature. These 7 tumors appear to be a type of primary central nervous system neoplasm which lacks markedly anaplastic features and exhibits locally aggressive behavior.

Adult↗