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F W Abdul-Karim

Publications and source records attributed to F W Abdul-Karim.

At least 19 recordsLinked to original sources
PubMed2006

Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2/Neu-induced tumors.

Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting that additional events are required for ErbB2/Neu to cause mammary tumors. Whether such events are genetic in nature or reflective of the dynamic hormonal control of the gland that occurs with pregnancy remains unclear. We postulated that young age at pregnancy initiation or chronic trophic maintenance of mammary epithelial cells might provide a cellular environment that significantly increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that were maintained pregnant or lactating beginning at 3 weeks of age demonstrated accelerated tumorigenesis, but this process was still stochastic, indicating that early pregnancy does not provide the requisite events of tumorigenesis. However, bitransgenic mice that were generated by breeding MMTV-Neu mice with a luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation developed multifocal mammary tumors in an accelerated, synchronous manner compared to virgin MMTV-Neu animals. This synchrony of tumor development in the bitransgenic mice suggests that trophic maintenance of the mammary gland provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of tumor appearance and the ability to characterize a window of commitment by ovariectomy/palpation studies permitted microarray analysis to evaluate changes in gene expression over a defined timeline that spans the progression from normal to preneoplastic mammary tissue. These approaches led to identification of several candidate genes whose expression changes in the mammary gland with commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be regulated by ErbB2/Neu and/or contribute to tumor formation.

Animals↗
PubMed2005

Angiosarcoma arising in an arteriovenous fistula site in a renal transplant patient: a case report and literature review.

Angiosarcoma in the setting of immunosuppressed renal transplant recipients is exceedingly rare. In this report, we describe the occurrence of angiosarcoma arising at an arteriovenous fistula site of a 39-year-old renal transplant recipient that clinically mimicked a thrombosed aneurysm. These tumors are histologically high-grade and clinically aggressive malignancies. They have a predilection for arteriovenous fistula sites. The literature on this uncommon entity is reviewed and possible histogenesis is discussed.

Adult↗
PubMed2001

Molecular evidence for the independent origin of extra-ovarian papillary serous tumors of low malignant potential.

BACKGROUND: Molecular data suggest that peritoneal tumors in women with advanced-stage ovarian papillary serous adenocarcinoma are monoclonal in origin. Whether the same is true for ovarian tumors of low malignant potential is not known. We compared peritoneal and ovarian tumors from women with advanced-stage ovarian papillary serous tumors of low malignant potential to determine whether the peritoneal tumors arose from the same clone as the ovarian tumors. METHODS: We studied the clonality of 73 peritoneal and ovarian tumors from 18 women with advanced-stage ovarian papillary serous tumors of low malignant potential. Formalin-fixed, paraffin-embedded tumors and representative normal tissues were sectioned and stained with hematoxylin-eosin, representative sections from separate tumors were manually microdissected, genomic DNA was extracted from the microdissected tumors, and the polymerase chain reaction was used to amplify a CAG polymorphic site in the human androgen receptor locus on the X chromosome to determine the inactivation pattern of the X chromosome and the clonality of the tumors. RESULTS: The pattern of X-chromosome inactivation could be determined from the tumors of 13 of 18 patients. Of the 13 patients, seven (54%) had nonrandom inactivation of the X chromosome, and six of the seven had different inactivation patterns in the peritoneal and ovarian tumors. Three of these patients also had different patterns of nonrandom X-chromosome inactivation in tumors from each ovary. The remaining six patients had random patterns of X-chromosome inactivation in the peritoneal and ovarian tumors. CONCLUSIONS: Our data suggest that peritoneal and ovarian tumors of low malignant potential arise independently.

Adenocarcinoma, Papillary↗
PubMed2001

Systemic deficits in transporter for antigen presentation (TAP)-1 or proteasome subunit LMP2 have little or no effect on tumor incidence.

Some tumor cells have deficits in class I MHC antigen processing, suggesting that T cells exert selective pressure on tumor cells. Previous studies have not revealed increased tumor incidence in mice with deficits in T-cell immunity, including mice lacking TAP1 (a subunit of the transporter for antigen presentation) or LMP2 (a regulated subunit of the 20S proteasome). The incidence of spontaneous tumors in these mice, however, is too low to assess differences in host resistance to tumors. To increase tumor incidence and better assess the role of systemic expression of TAP1 and LMP2 in responses to tumors, TAP1-/- and LMP2-/- mice were bred with p53-/- mice to create TAP1-/-p53-/- and LMP2-/-p53-/- double knockout mice. Lymphomas and sarcomas (malignant fibrous histiocytoma and angiosarcoma) occurred with high incidence in all p53-deficient populations. Tumor incidence and death rate were similar in TAP1-/-p53-/- mice and closely matched control TAP1+/+p53-/- mice. Tumor incidence and death rate were slightly accelerated in LMP2-/-p53-/- mice relative to control LMP2+/+p53-/- mice, but the biological significance of this difference was unclear. The relative incidence of lymphomas vs. sarcomas was not significantly altered by variation in TAP1 or LMP2. In conclusion, systemic absence of TAP1 did not alter tumor incidence, while absence of LMP2 was associated with only a slight acceleration of tumor incidence of uncertain significance. These observations are consistent with other evidence that normal T-cell responses do not effectively limit tumorigenesis. Even though T cells can attack some tumor cells, the ability of tumors to alter their immunogenicity and evade T-cell surveillance may render the native immune system ineffective at providing a rate-limiting barrier to tumorigenesis and preventing cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Positive emission tomography for evaluating a complete clinical response in patients with ovarian or peritoneal carcinoma: correlation with second-look laparotomy.

OBJECTIVE: Positive emission tomography (PET) provides a novel means of imaging malignancies. The following study was undertaken to evaluate the predictive value of PET in determining a pathologic complete response in patients with advanced ovarian or peritoneal carcinoma who had a complete clinical response following primary chemotherapy. METHODS: Twenty-two patients with advanced-stage ovarian (N = 17) or peritoneal (N = 5) carcinoma who had achieved complete clinical and radiologic remission and normal CA-125 level after six cycles of chemotherapy and who had consented to a second look laparotomy procedure were studied. All patients received platinum based therapy and all but one patient, treated elsewhere, received paclitaxel in combination with platinum. Following IV administration of 20 mCi [(18)F]fluorodeoxyglucose (FDG), the entire abdomen and pelvis were scanned. Various technical modifications including bladder activity dilution, intravenous hydration with diuretic therapy, and mechanical bowel preparations, were used to reduce background activity. Second-look laparotomy findings were classified as negative, macroscopically positive if a biopsy of a suspicious area was histologically positive, or microscopically positive if only a nonsuspicious area was histologically positive. The effect of patient preparation prior to PET imaging was evaluated. RESULTS: Persistent disease was found in 13 of the 22 patients (59%). Only one of nine sites with macroscopic and none of four with microscopic disease were accurately predicted. The sensitivity was only 10% and the specificity 42%. Intravenous hydration, diuretic therapy, and bowel preparation did not improve the results. CONCLUSIONS: These results suggest that despite technical modifications the sensitivity of PET before second-look laparotomy for small-volume persistent disease is low.

Adenocarcinoma, Mucinous↗
PubMed2001

Florid vascular proliferation of the colon related to intussusception and mucosal prolapse: potential diagnostic confusion with angiosarcoma.

With the exception of angiodysplasia, vascular abnormalities of the intestines are unusual. We describe a florid benign vascular proliferation of the colon in five adult patients, three of whom presented with idiopathic intussusception. In all cases, the proliferation was sufficiently exuberant to raise the possibility of angiosarcoma as a diagnostic consideration. The group included 2 males and 3 females with a median age of 43 years. Two patients were HIV positive. Four patients presented with a colonic mass; other symptoms at presentation included abdominal pain, diarrhea, bleeding, and bowel obstruction. In all cases, a florid lobular proliferation of small vascular channels lined by plump endothelial cells extended from the submucosa through the entire thickness of the bowel wall. The endothelial cells showed minimal nuclear atypia, and mitotic figures were infrequent. The overlying mucosa showed ulceration with ischemic-type changes, and had features of mucosal prolapse. A possible underlying arteriovenous malformation was identified in two cases. All patients were alive and well at last follow-up (interval, 6 months to 5 years). The presence of intussusception or mucosal prolapse in all of the cases suggests repeated mechanical forces applied to the bowel wall as a possible etiologic factor. The role of HIV infection in the pathogenesis of these lesions remains to be determined.

Adult↗
PubMed2001

Molecular genetic evidence for different clonal origin of components of human renal angiomyolipomas.

Renal angiomyolipoma is a benign neoplasm composed of variable proportions of blood vessels, smooth muscle, and adipose tissue. Smooth muscle, adipose tissue, blood vessels, and adjacent normal kidney tissue were separately microdissected from sections prepared from formalin-fixed, paraffin-processed tissues from angiomyolipomas from 18 women. X chromosome inactivation analysis using the methylation pattern at exon 1 of the human androgen receptor gene on chromosome Xq11-12 was used to study the clonal origin of each component. Nonrandom inactivation of X chromosomes was found in six of the 15 informative tumors. The smooth muscle and adipose tissue showed differing patterns of nonrandom inactivation of X chromosomes in five angiomyolipomas and the same pattern of nonrandom inactivation of X chromosomes in one. Samples from the blood vessels showed random inactivation of X chromosomes in all informative cases. Our data showed that the adipose tissue and smooth muscle cells of renal angiomyolipoma are both monoclonal but may arise independently. The coexistence of tumor subclones with morphologic heterogeneity can lead to the formation of a clinically detectable tumor.

Adipose Tissue↗
PubMed2001

Treatment of collagen induced arthritis by proteolytic enzymes: immunomodulatory and disease modifying effects.

OBJECTIVE: To investigate the efficacy of a novel therapy (proteases) in an animal model of rheumatoid arthritis, and to investigate the mechanisms of arthritogenesis. METHODS: We induced progressive arthritis in male DBA/1 mice by immunization and boosting with Type II collagen; groups of mice were treated orally twice daily with either ibuprofen or proteases, or were left untreated. After 2 weeks, joints were scored for clinical, radiographic, and histologic changes. In addition, we measured serum levels of IgG anti-collagen II, the glycosylation of circulating total and anti-collagen II IgG, and cytokine production by lymphocytes isolated from lymph nodes. RESULTS: Amelioration of joint inflammation, and accentuation of a prototypical Th2 cytokine (interleukin 5) were similar in the ibuprofen and protease treatment groups. However, protease treatment protects and preserves articular cartilage, normalizes the sialylation of IgG and anti-collagen antibody, and fully restores Th1 (interferon-gamma) synthesis, distinct from ibuprofen. CONCLUSION: Protease therapy has antiinflammatory efficacy in the early (inflammatory) phase of collagen induced arthritis, similar to ibuprofen. The immunomodulatory effects of proteases, not seen with ibuprofen, may underlie a correction of aberrant IgG glycosylation and/or contribute to the increased capacity of protease to delay or forestall erosive and destructive arthritis or ankylosis. Similar effects may apply to spontaneous RA in humans.

Animals↗
PubMed2000

Luteinizing hormone induction of ovarian tumors: oligogenic differences between mouse strains dictates tumor disposition.

The use of fertility drugs has continued to grow since their introduction in the 1960s. Accompanying this increase has been the speculation that repetitive use of these drugs can cause ovarian tumors or cancer. We recently reported that transgenic mice with chronically elevated luteinizing hormone (LH), an analog of which is commonly used in fertility regimens, develop granulosa cell (GC) tumors. In this report we show that LH induction of these tumors is highly dependent on genetic background. In CF-1 mice, chronically elevated LH invariably causes GC tumors by 5 months of age. However, in hybrid mice generated by crossing CF-1 males with C57BL/6, SJL, or CD-1 females, elevated levels of this same hormone cause a completely different phenotype resembling a luteoma of pregnancy. We also show that three genes likely control these alternative hormonal responses. This clinical correlate of elevated LH reveals remarkably distinct, strain-dependent, ovarian phenotypes. In addition, these results support the rare incidence of GC tumors in the human population, and suggest that the ability of certain fertility drugs to cause ovarian tumors may depend on an individual's genetic predisposition.

Animals↗
PubMed2000

Papillary squamous cell carcinomas of the upper aerodigestive tract: a clinicopathologic and molecular study.

BACKGROUND: The limited studies and the small number of published cases of papillary squamous cell carcinoma have precluded accurate assessment of the biologic characteristics of this lesion. METHODS: Thirty-eight of the carcinomas were studied. In-situ hybridization and polymerase chain reaction were performed to detect human papilloma virus (HPV) and p53 expression. RESULTS: HPV was found in 4 of 14 assessable carcinomas by in-situ hybridization and in 5 of 14 by polymerase chain reaction. The most frequently identified HPVs were HPVs in 6/11 and 16/18 patients. In general, a reciprocal relationship was found between p53 and HPV prevalence. The most lethal site for this tumor was the sinonasal tract, whereas patients with papillary squamous cell carcinomas of the larynx had the best outlook. Eleven of 25 (44%) assessable patients died of disease (mean time interval, 2 year). CONCLUSIONS: Papillary squamous cell carcinoma of the upper aerodigestive tract is a distinct variant of squamous cell carcinoma. As such and because of its putative association with HPV, papillary squamous cell carcinoma could be an informative model for defining how viral oncogenes cooperate with other factors in genomic instability, carcinogenesis, and tumor development.

Adult↗
PubMed2000

Evidence for the neoplastic transformation of Von-Meyenburg complexes.

Von-Meyenburg complexes (VMC) are seen frequently in the liver and are largely considered to be innocuous, with only 11 cases reported in the literature of neoplastic transformation of VMCs. The authors report three cases of cholangiocarcinoma, each occurring in a background of fibrosis and nodularity that was reported initially as micronodular cirrhosis. Although the livers showed cirrhosis, the central veins were often preserved, and regenerative activity was patchy and focal. Histologic examination revealed many VMCs, and a gradual transition from VMCs to hyperplastic or adenomatous lesions and cholangiocarcinoma. The adenomatous lesions consisted of extensive replacement of the parenchyma by tumor-like nodules of ductular proliferations without obvious features of malignancy. All three patients were older than 60 years of age and had portal hypertension. Computed tomographic scans showed multiple, small renal cysts in one patient. Immunohistochemical staining showed positivity for epithelial membrane antigen, carcinoembryonic antigen, and keratins (AE1/AE3 and CAM5.2) in tumor cells, consistent with cholangiocarcinoma. The pattern of fibrosis and nodularity in these cases is not typical of either congenital hepatic fibrosis or usual cirrhosis. The authors propose that these patients represent another aspect in the spectrum of ductal plate malformations that may be modified by other factors such as alcohol, drugs, or infection. To their knowledge, neoplastic transformation of VMCs in the background of such changes has never been reported before.

Aged↗
PubMed2000

Histological study of injected autologous fascia in the paralyzed canine vocal fold.

OBJECTIVE: Several methods have been used for the treatment of the unilateral paralyzed vocal fold. Teflon injections have been used extensively but not without complications. The ideal substance for injection is yet to be determined. Injected autologous fascia has been reported as a means of achieving glottic closure. In review of the literature, there are no long-term results described using autologous fascia in this way. The purpose of this study was to examine the histological changes of the larynx after injection of autologous fascia into a paralyzed vocal fold. STUDY DESIGN: A prospective study with the contralateral side of the larynx used as the control. METHODS: Six adult dogs underwent severing of one of their recurrent laryngeal nerves. After the vocal folds were confirmed to be paralyzed by direct laryngoscopy, fascia lata that was harvested from the animal was minced and injected into the paralyzed vocal fold. The dogs were then killed at intervals ranging from 3 to 12 months and their larynges reviewed histologically. RESULTS: The larynges revealed muscle atrophy of the vocal fold, which is consistent with denervation, but there was no evidence of persistent fascia. In addition, there was no evidence of reaction to the injected fascia. Special stains for collagen were also performed which showed no significant change from the non-injected vocal fold. CONCLUSION: From this model, it is concluded that injected autologous minced fascia is not a good short- or long-term substance for vocal fold augmentation. Further study is warranted to confirm this observation.

Animals↗
PubMed1999

Positron emission tomography for evaluating para-aortic nodal metastasis in locally advanced cervical cancer before surgical staging: a surgicopathologic study.

PURPOSE: Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS: After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS: Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION: Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.

Aorta↗
PubMed1999

Atypical teratoid/rhabdoid tumor of the CNS: cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin D, and Ki-67.

Insulin-like growth factor (IGF)-II is a potent growth factor, normally controlled by a number of other factors, including IGF binding proteins and IGF binding protein proteases. In general, the latter increase the bioavailability of IGF by cleaving IGF binding proteins. Cathepsin D (an IGF binding protein protease) was also implicated in tumor invasion. Although IGF-II was implicated in the pathogeneses of various childhood neoplasms, its significance in the pathogenesis of atypical teratoid/rhabdoid tumor of the central nervous system (ATRT-CNS) was not studied to date. We present clinicopathologic features of two cases of ATRT-CNS. In addition, formalin-fixed, paraffin-embedded tissue sections were stained immunohistochemically for IGF-II, IGF receptor type 1, cathepsin D, and Ki-67. Both tumors demonstrated diffuse strong cytoplasmic positivity for IGF-II, diffuse cytoplasmic and focal membranous positivity for IGF receptor type I, and diffuse cytoplasmic positivity for cathepsin D. The Ki-67 labeling indices were 10.0% and 1.4%. We conclude that ATRT-CNS cells express both IGF-II and IGF receptor type 1, supporting the hypothesis that autocrine/paracrine stimulation of cell growth by IGF-II might be one mechanism involved in ATRT-CNS tumorigenesis. Cathepsin D expressed by the tumor cells might also be involved in both tumor cell invasion and growth. The exact pathogenesis of ATRT-CNS remains to be elucidated.

Adolescent↗
PubMed1999

Analysis of ovarian borderline tumors using comparative genomic hybridization and fluorescence in situ hybridization.

It is unclear whether ovarian borderline tumors (tumors of low malignant potential) are independent entities or whether they are part of a continuum of tumor progression that culminates in ovarian carcinoma. Little is known about genetic abnormalities in borderline tumors because of the difficulty of growing them in culture for chromosome studies, and because the low ratio of tumor to nontumor cells can interfere with molecular genetic examination. To circumvent these problems, we performed comparative genomic hybridization (CGH) on 10 serous borderline tumors from nine patients, using microdissection to enrich the samples for tumor DNA and reduce contamination from stromal and inflammatory cells. CGH analysis revealed that three of the tumors had detectable chromosomal imbalances, whereas seven were in a balanced state. In those tumors with imbalances, the number of abnormalities ranged from 3-6 per tumor. Additional studies by fluorescence in situ hybridization (FISH) on disaggregated nuclei confirmed the imbalances detected by CGH, revealed one tumor to be hypertriploid, and indicated that the remaining tumors were diploid and in a balanced state. All abnormalities observed in the aneuploid cases are consistent with chromosomal aberrations previously reported for ovarian carinomas, providing further evidence that some borderline tumors are part of a continuum of tumor progression. These results also suggest that there may be different mechanisms leading to borderline tumor formation, including one associated with multiple chromosomal imbalances, and others that do not involve imbalances detectable by CGH. Genes Chromosomes Cancer 25:307-315, 1999.

Adult↗