Biomedical subjects

K R Cleary

Publications and source records attributed to K R Cleary.

At least 55 records · Page 3Linked to original sources

PubMed1995

Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.

We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors with vascularity, metastasis, and proliferative index of human colon cancers. Immunohistochemical analyses using antibodies against VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII, and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were quantitated by light microscopy (x200), and the intensity of staining for VEGF and bFGF was assessed on a scale of 0-3+. The presence or absence of immunostaining for KDR, flt-1, bek, and flg was evaluated in endothelial cells, and proliferation was determined by counting the number of proliferating cell nuclear antigen-positive cells per 500 tumor cells. Expression of VEGF and KDR was higher in metastatic than in nonmetastatic neoplasms and directly correlated with the extent of neovascularization and the degree of proliferation, whereas expression of bFGF, flt-1, bek, and flg did not differ among tumor types. Vessel counts were greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression and vessel counts may aid in predicting patients at risk for metastasis from colon cancer.

Adenoma↗

PubMed1995

Preoperative infusional chemoradiation therapy for stage T3 rectal cancer.

PURPOSE: To evaluate preoperative infusional chemoradiation for patients with operable rectal cancer. METHODS AND MATERIALS: Preoperative chemoradiation therapy using infusional 5-fluorouracil (5-FU), (300 mg/m2/day) together with daily irradiation (45 Gy/25 fractions/5 weeks) was administered to 77 patients with clinically Stage T3 rectal cancer. Endoscopic ultrasound confirmed the digital rectal exam in 63 patients. Surgery was performed approximately 6 weeks after the completion of chemoradiation therapy and included 25 abdominoperineal resections and 52 anal-sphincter-preserving procedures. RESULTS: Posttreatment tumor stages were T1-2, N0 in 35%, T3 N0 in 25%, and T1-3, N1 in 11%; 29% had no evidence of tumor. Local tumor control after chemoradiation was seen in 96% (74 out of 77); 2 patients had recurrent disease at the anastomosis site and were treated successfully with abdominoperineal resection. Overall, pelvic control was obtained in 99% (76 out of 77). The survival after chemoradiation was higher in patients without node involvement than in those having node involvement (p = n.s.). More patients with pathologic complete responses or only microscopic foci survived than did patients who had gross residual tumor (p = 0.07). The actuarial survival rate was 83% at 3 years; the median follow-up was 27 months, with a range of 3 to 68 months. Acute, perioperative, and late complications were not more numerous or more severe with chemoradiation therapy than with traditional radiation therapy (XRT) alone. CONCLUSIONS: Excellent treatment response allowed two-thirds of the patients to have an anal-sphincter-sparing procedure. Gross residual disease in the resected specimen indicates a poor prognosis, and therapies specifically targeting these patients may improve survival further.

Adenocarcinoma↗

PubMed1995

Preoperative infusional chemoradiation and surgery with or without an electron beam intraoperative boost for advanced primary rectal cancer.

PURPOSE: To compare the multimodality treatment results of surgical resection plus preoperative radiotherapy with concomitant protracted infusion chemotherapy (preop-chemoXRT), with or without an electron beam intraoperative radiotherapy (EB-IORT) boost, in 37 patients having advanced primary rectal cancer, with the results of a protocol using only preoperative radiotherapy (preop-XRT) plus surgical resection in a historic control group of 36 patients. METHODS AND MATERIALS: Thirty-eight patients with tethered T3 or T4 primary rectal cancer were treated with 45 Gy delivered in 25 fractions over 5 weeks plus infusional chemotherapy. Thirty-seven patients underwent surgical resection: 13 (35%) had restorative operations, and the remainder had either abdomino-perineal resection (APR) or pelvic exenteration (PE). Electron beam intraoperative radiotherapy (EB-IORT) was used in doses of 10-20 Gy for 11 patients with adherent pelvic tumor. In the 36 historic control patients, the preop-XRT dose was 45 Gy, and 93% of them had APR or PE. RESULTS: The local recurrence rate was 3% for the preop-chemoXRT group and 33% for the historic control group. The 3-year survival rate for patients treated with preop-chemoXRT plus resection was 82% compared with 62% for the historic control group. Distant metastases occurred more frequently in patients treated with an EB-IORT boost than in patients who were not (64% vs. 19%, p < 0.05), and the overall 3-year survival rate was lower for the former (67% vs. 96%, p < 0.05). Acute and late toxicities were acceptable. CONCLUSIONS: Preop-chemoXRT for advanced primary rectal cancer results in better control of pelvic disease and better overall survival rates than does preop-XRT alone. With preop-chemoXRT, acute chemoradiation toxicity is increased whereas late morbidity is unchanged compared with preop-XRT alone. Local control in patients with areas of residual or clinically adherent disease is improved by the use of EB-IORT; however, patients treated with EB-IORT had poorer survival rates than those treated without EB-IORT.

Adult↗

PubMed1995

bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis.

Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.

Adenocarcinoma↗

PubMed1995

Mycobacterial disease of the head and neck: current perspective.

The worldwide increase in mycobacterial diseases, tuberculous and nontuberculous, and their association with human immunodeficiency virus infection has had and will continue to have an impact on the practice of otolaryngologist-head and neck surgeons. Epidemiologic and ecologic changes in tuberculosis and nontuberculous mycobacterial diseases tend to blur former clinicopathologic distinctions among these groups, especially in immunocompromised hosts. Diagnosis depends on objective identification of the mycobacterium, a process facilitated by molecular diagnostics.

Adolescent↗

PubMed1995

Oral squamous cell carcinoma and the mandible.

Of the various oral carcinoma subsites, the carcinomas related to the mandibular region (alveolar ridge, floor of mouth, lower retromolar area, lower buccal sulcus) are among those with the highest rate of recurrences. Neoplastic invasion of the mandible is one of the factors promoting the recurrences. Determining the presence and extent of bony involvement is therefore critical in the management of patients. The surgeon has several methods to aid in the determination of margins of invasion: radiology, gross clinical inspection, and intraoperative frozen section. Each has its deficiences and in the end, it is a combination of the methods, tempered by clinical judgment, that produces the best results.

Carcinoma, Squamous Cell↗

PubMed1995

Rapid-fractionation pre-operative chemoradiation for malignant periampullary neoplasms.

The multimodality treatment of adenocarcinoma of the pancreatic head has been shown to improve survival compared with surgery alone. The delivery of chemotherapy and radiation therapy (chemoradiation) before rather than after pancreaticoduodenectomy ensures that all patients who undergo surgery receive the other components of multimodality therapy. In an effort to reduce overall treatment time and cost, the use of rapid-fractionation preoperative chemoradiation was explored. Radiation therapy was delivered with 18-MeV photons to a total dose of 30 Gy given in 10 fractions over 2 weeks. 5-Fluorouracil was given concurrently by continuous infusion at a dose of 300 mg m-2 day-1. Four weeks after the completion of chemoradiation, patients underwent pancreaticoduodenectomy and electron-beam intraoperative radiation therapy (10 Gy). All patients completed the treatment programme without delay. The rapid-fractionation programme was delivered at nearly half the cost of standard chemoradiation and histologic evidence of tumour cell injury was present in all resected specimens. There were no perioperative anastomotic complications, and median hospital stay was 20 days. Rapid-fractionation chemoradiation warrants further study in the neoadjuvant setting.

Adenocarcinoma↗

PubMed1994

Primary intraspinal soft-tissue sarcoma in childhood: report of two cases with a review of the literature.

Two young children who presented with lower spinal cord dysfunction manifested by bilateral leg weakness and urinary retention were diagnosed with intraspinal soft-tissue sarcoma. Neither patient had a significant extradural mass. Both tumors had histochemical features of rhabdomyosarcoma. Temporary responses were noted after combination chemotherapy either with vincristine, actinomycin D, and cyclophosphamide or with ifosfamide/mesna and etoposide. However, both patients developed uncontrollable cerebrospinal fluid (CSF) dissemination of tumor and died within 6 months of diagnosis, despite intrathecal chemotherapy and irradiation for one and very high-dose intravenous methotrexate (33 g/m2) for the other. This rare tumor can respond to parenteral antisarcoma chemotherapy, but better strategies are needed to prevent CSF spread and ultimate demise. Early institution of intrathecal cytostatic agents may retard or prevent CSF dissemination and prolong survival.

Child, Preschool↗

PubMed1994

Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms.

A prospective diagnostic study was designed to determine the ability of thin-section contrast-enhanced computed tomography (CT) to predict the resectability of malignant neoplasms of the pancreatic head. Patients with a presumed resectable pancreatic neoplasm referred during a 21-month period were studied with abdominal CT performed at 1.5-mm section thickness and 5-mm slice interval during the bolus phase of intravenous contrast enhancement. CT criteria for resectability included the absence of extrapancreatic disease, no evidence of arterial encasement, and a patent superior mesenteric-portal venous confluence. Of 145 patients evaluated, 42 were considered to have resectable tumors by CT criteria, and 37 (88%) underwent potentially curative pancreaticoduodenectomy. Six patients were found to have a microscopically positive retroperitoneal resection margin; no patient had a grossly positive resection margin. Five (12%) of 42 patients were found at laparotomy to have unresectable, locally advanced or metastatic tumors. Thin-section contrast-enhanced CT is an essential component of the preoperative evaluation for pancreaticoduodenectomy and can prevent needles laparotomy in most patients with locally advanced or metastatic disease.

Adenocarcinoma↗

PubMed1994

MUC1 mucin expression as a marker of progression and metastasis of human colorectal carcinoma.

BACKGROUND/AIMS: The MUC1 mucin distributes among a variety of epithelial tissues (except the intestinal epithelia) and is often detectable in colorectal carcinoma tissues and cell lines. This study aimed to elucidate whether MUC1 mucin expression correlated to the progression of colorectal carcinomas. METHODS: We collected 113 tissue specimens, including primary colorectal carcinoma, normal mucosa, liver metastases, lymph node metastases, and normal livers from 58 patients with colorectal carcinoma. Immunohistochemical staining and Western blotting analysis with mature MUC1 mucin-specific monoclonal antibodies were performed. RESULTS: The levels of mature MUC1 mucins were significantly higher in carcinoma tissues than those in normal colonic mucosa (P < 0.001). Furthermore, the levels of mature MUC1 mucins were significantly higher in primary tumors from patients having metastasis or metastatic tumors than in primary tumors from patients without metastasis (P < 0.001). In the primary sites, mature MUC1 mucin levels apparently increased according to progression of the stages (P < 0.001). CONCLUSIONS: These results strongly suggest that mature MUC1 mucins become ectopically expressed in colorectal carcinoma progressed to the metastatic stages and that mature MUC1 mucins may be a useful marker for advanced colorectal carcinoma.

Adult↗

PubMed1994

Hepatic arterial infusion of verapamil and doxorubicin with complete hepatic venous isolation and extracorporeal chemofiltration: pharmacological evaluation of reduction in systemic drug exposure and assessment of hepatic toxicity.

Tumour resistance to chemotherapeutic drugs through expression of the multidrug resistance phenotype is a major impediment in the treatment of hepatic malignancies. We performed hepatic arterial infusion of verapamil (at a dose known to block P-glycoprotein activity) and doxorubicin combined with complete hepatic venous isolation and extracorporeal chemofiltration in non-tumour-bearing pigs with normal livers to evaluate the pharmacology and toxicology of this drug combination. The complete hepatic venous isolation-chemofiltration system significantly reduced system exposure to both verapamil and doxorubicin (P < 0.01). Hepatic arterial infusion of verapamil (2 mg/kg) alone did not result in hepatocellular toxicity. However, the combination of verapamil and doxorubicin (3 mg/kg or 5 mg/kg) produced significant elevations in liver enzymes (P < 0.01), and gross histological evidence of liver damage in 90% of the treated animals. The results of this study indicate that hepatic arterial infusion of verapamil and doxorubicin, in an attempt to improve treatment response in unresectable liver tumours expressing the multidrug resistance phenotype, may not be tolerated by patients with limited hepatic reserve.

Animals↗

PubMed1994

Lichen planus and lichenoid lesions of the oral cavity.

Lichen planus is a mucocutaneous disease of unknown cause that has its principal clinical manifestations in the skin and mucosa of the oral cavity. The natural history of the cutaneous form is one of spontaneous resolution over time, while oral lichen planus pursues a much more chronic course with a low order of resolution. Oral lichen planus must be distinguished from lichenoid lesions, including lichenoid dysplasia. Malignant change in oral lichen planus is rare and is prompted by carcinogenic cofactors. There is no increased risk of development of carcinoma in cutaneous lichen planus.

Carcinoma, Squamous Cell↗

PubMed1994

Sinonasal lymphomas.

Advances in immunocytochemical phenotyping and molecular genetics have nearly resolved the histopathologic and therapeutic quandaries brought about by a diagnostic nomenclature that provided little guidance in the management of midfacial necrotizing lesions. Gone are terms like midline granuloma syndrome, lethal midline granuloma, polymorphic reticulosis, lymphomatoid granulomatosis, midline destructive granuloma, and idiopathic midline destructive disease. They have been replaced by the appreciation that the majority of the lesions are lymphomas of the sinonasal tract. The lymphomas are of B- or T-cell lineage and have a broad biologic spectrum from low to high grade. Still to be addressed are apparent geographic differences in biologic behavior, the epidemiologic significance of a preponderance of T-cell nasal lymphomas in the Orient, and optimum therapeutic regimens.

Humans↗

PubMed1994

Immunohistochemical analysis of p53 overexpression in human colonic tumors.

The progression from benign adenoma to colorectal cancer is underscored by an accumulation of genetic defects involving the activation of protooncogenes and the inactivation by point mutations and deletions of tumor-suppressor genes. Altered p53 has been one of the most commonly observed of these defects. By using a monoclonal antibody, PAb1801, it was possible to detect the accumulation of an altered p53 protein in standard sections of colon-preserving histopathological criteria. We analyzed biopsies from benign and malignant colorectal tumors fixed in 70% ethanol, and detected cells positive for p53 in 65% of 34 carcinomas and 24% of 84 adenomas, but none in the normal-appearing adjacent mucosa. No correlation was found between degree of differentiation of adenocarcinomas and p53 immunodetection. Abnormal p53 protein expression in adenomas ranged from sparsely stained to focally intensive areas. Overexpression of p53 was detected in more tumors taken from the left side of the colon than from the right side. Adenomas with greater villous content and severe dysplasia had a greater tendency to overexpress mutated p53. Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma. Immunodetection of p53 in 11 biopsies from the same tumors alternatively fixed in 70% ethanol or formalin gave comparable results for adenocarcinomas but was not consistent for adenomas. Fifty-four archival formalin-fixed paraffin-embedded colorectal tumors were also stained with PAb1801. p53 was detectable, sometimes with a weaker intensity, in 50% of 18 adenocarcinomas and 22% of 36 adenomas, and most of these showed severe dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1994

Assessment of Ki-67-derived tumor proliferative activity in colorectal adenocarcinomas.

Analysis of tumor growth fraction (TGF) has become essential as cell cycle-directed modalities have been increasingly used for the treatment of solid neoplasms. We studied TGF in fresh tissue samples from 74 surgically resected colorectal carcinomas (50 colon and 24 rectum; 44 men and 30 women) by flow cytometry (FCM) and by immunostaining using Ki-67 monoclonal antibody. In 12 cases, samples of uninvolved colonic mucosa adjacent to tumor (transitional mucosa) and samples of normal mucosa (at least 5 cm away from tumor) were available for growth fraction analysis. The mean Ki-67 and S-phase values were 17.1% (range, 0-60%) and 17.5% (range, 3-39%), respectively. The mean percentage of Ki-67 positivity in tumor samples from women was significantly lower than that in samples from men (P = 0.001). Ki-67-derived TGF values, however, did not correlate with patient age, lymph node status, or tumor size, site, stage, degree of differentiation, or DNA ploidy. The correlation between Ki-67-derived and FCM-derived TGF values was statistically significant (P = 0.001) but marginal (R = 0.35). In both transitional and normal colonic mucosa samples, Ki-67 positivity was mainly confined to the lower half of the crypts, and their growth fraction values were significantly lower than those of tumor tissue; however, there was no difference in values between transitional and normal mucosae. Our results indicate that Ki-67-derived TGF does not correlate with known prognostic factors for colorectal carcinoma; however, long-term follow-up information will be necessary to define the clinical value of Ki-67 staining.

Adenocarcinoma↗

PubMed1993

A rapid colorimetric in situ messenger RNA hybridization technique for analysis of epidermal growth factor receptor in paraffin-embedded surgical specimens of human colon carcinomas.

We have developed a rapid colorimetric in situ mRNA hybridization procedure to analyze epidermal growth factor receptor (EGF-R) transcripts in paraffin-embedded surgical specimens of human colon carcinomas. This technique is based on the use of 24-base oligonucleotide probes labeled with 6 biotin molecules at the 3' end. mRNA integrity was verified using a hyperbiotinylated 30-residue-long deoxythymidylate oligonucleotide probe, and the specificity of the reaction was confirmed by using labeled EGF-R-specific sense and antisense probes. Avidin alkaline phosphatase detection and the capillary technology used in the Microprobe System allowed for completion of the procedure in under 5 h. The human A431 epidermoid carcinoma cells growing in culture and fixed with formalin as well as paraffin-embedded sections of this tumor growing s.c. in nude mice served as positive controls. In situ hybridization with antisense EGF-R oligonucleotide probes directly correlated with EGF-R mRNA and protein levels observed by Northern blot and immunohistochemistry, respectively. In situ hybridization of paraffin-embedded sections of primary human colon carcinoma and metastases from liver and lymph node revealed cell-specific staining with EGF-R antisense oligonucleotide probes that correlated directly with Northern blot and immunohistochemistry analyses. Since this rapid and sensitive in situ mRNA hybridization technique can be used in properly preserved paraffin-embedded tissue, it allows for retrospective analyses of human tumor specimens using archival material.

Animals↗

PubMed1993

Overexpression of an elongation factor-1 gamma-hybridizing RNA in colorectal adenomas.

While it is apparent that colorectal carcinogenesis results from a series of genetic alterations manifested phenotypically by the adenoma-to-carcinoma sequence, the early events that occur in the process of tumorigenesis have not been elucidated. We previously demonstrated that human elongation factor-1 (EF-1) gamma-hybridizing RNA was overexpressed in 25 of 29 colorectal carcinomas. To determine if the overexpression of this mRNA occurs early in tumor development, we examined 25 adenomas and corresponding normal-appearing distant mucosae from 20 patients without familial adenomatous polyposis (FAP). We observed overexpression at a level of twofold or more in 14 (56%) of the 25 adenomas, indicating that overexpression of EF-1 gamma RNA is often a relatively early event in the development of non-FAP colorectal cancer.

Adenoma↗

PubMed1993

Squamous odontogenic tumor.

The squamous odontogenic tumor is almost exclusively an intraosseous lesion of the jaw bones. Only 1 extraosseous variant has been reported. The tumor is histologically benign, with only occasional recurrences after surgical removal. Malignant alteration is unknown, but the lesion must be distinguished from intraosseous squamous cell carcinomas.

Carcinoma, Squamous Cell↗