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P L Baron

Publications and source records attributed to P L Baron.

At least 37 records · Page 2Linked to original sources

CaSm: an Sm-like protein that contributes to the transformed state in cancer cells.

A novel gene encoding a protein containing Sm motif-like domains was found to have elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm (for Cancer-associated Sm-like) mRNA is up-regulated in 87.5% (seven of eight) of pancreatic tumor/normal pairs. Similarly, cell lines from cancers originating in liver, ovary, lung, and kidney show increased CaSm expression compared to their normal tissue cognates. CaSm encodes a 133-amino acid open reading frame that contains the two Sm motifs found in the common snRNP proteins, with the greatest homology to the Sm G protein (60% similarity). Two hypothetical proteins from Caenorhabditis elegans and Saccharomyces cerevisiae share even greater similarity (72.8 and 67.7%, respectively), suggesting a broad family of proteins containing Sm motifs. Antisense CaSm RNA is able to alter the transformed phenotype of pancreatic cancer cells by reducing their ability to form large colonies in soft agar when compared to untransfected cells. Therefore, CaSm expression appears to be necessary for maintenance of the transformed state.

Amino Acid Sequence↗

p75 neurotrophin receptor induction and macrophage infiltration in peripheral nerve during experimental diabetic neuropathy: possible relevance on regeneration.

In this study we examined the expression of the neurotrophin receptor p75 (p75NTR) and the activation of macrophages in the sciatic nerve of rats at different time points after the induction of diabetes with streptozotocin (STZ). Northern blot and immunocytochemical analysis showed that p75NTR was not detectable in the sciatic nerve by Week 2 after STZ treatment. At this time, single nerve fiber immunostaining using ED1 monoclonal antibody revealed that active macrophages were infiltrating the endoneurium, which had a normal morphological aspect. By Weeks 5 and 15 p75NTR mRNA and protein were induced in the endoneurium of diabetic animals. Immunocytochemical analysis of teased single nerve fibers showed that p75NTR protein was distributed uniformly along isolated fibers with no pathological evidence of axonal degeneration or myelin disruption. At this time, cells of the phagocyte lineage had already disappeared from the nerve. These data show that during experimental diabetic neuropathy, the endoneurial induction of p75NTR is localized along isolated nerve fibers showing no morphological alterations, and in time, follows the recruitment of active macrophages in the nerve, suggesting that these cells, directly or through their products, can influence p75NTR induction. This process might play an important role in STZ diabetic neuropathy, as a response to decreased levels of neurotrophins such as NGF and promoting nerve regeneration in the early phases of the disease.

Animals↗

Magnetic resonance cholangiopancreatography: a novel approach to the evaluation of suspected pancreaticobiliary neoplasms.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive diagnostic method for pancreaticobiliary (PB) imaging without endoscopy, sedation, or iodinated contrast. The purpose of this study was to evaluate the ability of MRCP to depict pancreatic and biliary ductal anatomy compared to that of endoscopic retrograde cholangiopancreatography (ERCP) and to evaluate the ability of MRCP to accurately diagnose PB neoplasms. METHODS: Twenty patients had MRCP, and 17 also had ERCP. All studies were read prospectively by experienced reviewers blinded to other imaging data. Pathologic diagnosis was made in all patients. RESULTS: Bile duct dilatation seen by ERCP in 14 of 17 patients was correctly identified by MRCP in all 14 patients, and normal ducts were correctly identified by MRCP in the other 3 patients. The pancreatic duct was visible on MRCP in the pancreatic head in 17 of 20 patients, the body in 17 of 20 patients, and the tail in 15 of 20 patients. At ERCP, pancreatic duct dilatation was present in 11 cases and was identified by MRCP in 10 of them. Eighteen of 20 patients had malignant PB neoplasms. MRCP indicated PB neoplasm in 19 patients. Seventeen of these 19 patients had histologically confirmed malignant neoplasms pathologically, whereas 2 had benign pathology (both chronic pancreatitis). Among the 17 patients who also had ERCP, MRCP and ERCP correctly agreed on a final diagnosis of malignant neoplasm in 14 cases. In the three cases in which MRCP and ERCP disagreed on a final diagnosis, MRCP was correct in one and incorrect in two. CONCLUSIONS: MRCP can accurately and noninvasively delineate PB ductal anatomy and diagnose PB neoplasms comparably to ERCP. MRCP is an interesting new noninvasive method for evaluating patients with suspected PB neoplasms.

Bile Ducts↗

Differentiation of benign from malignant pancreatic masses by endoscopic ultrasound.

BACKGROUND: It is often difficult to determine whether a mass in the pancreas is benign or malignant. The goal was to evaluate whether endoscopic ultrasound (EUS) can reliably establish whether a mass is benign or malignant. METHODS: One hundred five patients with possible pancreatic tumors were referred for EUS. Those who were found to have a lesion suspicious for carcinoma and did not have a known malignancy also underwent EUS-guided FNA. RESULTS: A mass suspicious for cancer was identified in 73 patients, whereas inflammatory changes or a normal pancreas was noted in 32 patients. Four of the latter 32 patients were subsequently found to have cancer. EUS-guided FNA was performed on 47 of the 73 patients with a suspicious mass and was read as cancer in 27 patients, atypia in 10 patients, and benign in 10 patients. All 10 patients with atypia were subsequently confirmed to have cancer, and 6 of the 10 patients with a benign FNA were proved to have a tumor at surgery. EUS could differentiate the lesion as malignant with a sensitivity of 95%, specificity 88%, positive predictive value 95%, and negative predictive value 88%. CONCLUSIONS: Radial array EUS is helpful in supporting or refuting a diagnosis of cancer in a patient with a pancreatic mass. Although EUS-guided FNA can confirm the diagnosis, a negative FNA should not preclude exploration when clinically indicated.

Adenocarcinoma↗

p53 overexpression in squamous cell carcinoma of the esophagus.

BACKGROUND: Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of the p53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency of p53 overexpression in this region both in patients with SCCE and in normal subjects. METHODS: Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to the p53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of the p53 gene was amplified via polymerase chain reaction and sequenced. RESULTS: Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate for p53 overexpression. The corresponding normal samples showed that three (33%) had p53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayed p53 overexpression in seven (39%). Eight of the nine tumors had p53 mutations. CONCLUSIONS: p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region.

Antibodies, Monoclonal↗

Endoscopic ultrasound guided fine needle aspiration of malignant pancreatic lesions.

PURPOSE: To evaluate the accuracy, safety, and clinical utility of endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) of pancreatic masses. METHODS: Forty-seven patients were referred for EUS with a pancreatic mass and suspicion of pancreatic cancer based upon painless obstructive jaundice, epigastric abdominal pain plus weight loss/anorexia, or idiopathic pancreatitis. All patients underwent EUS with both radial (Olympus UM20) and linear array (Pentax FG32-UA) systems. After TNM staging by EUS, ultrasound directed FNA of the pancreatic mass was performed using a 23 gauge, 4 cm long needle. RESULTS: EUS-guided FNA was performed in all 47 patients. Results: successful targeting = 100%, adequate cellularity = 100%, FINDINGS: adeno Ca = 25, squamous cell Ca = 1, lymphoma = 1, poorly differentiated Ca= 1, atypical cytology or suspicious for carcinoma = 9, no malignant cells = 10. The sensitivity, specificity, positive predictive value and negative predictive value of EUS-guided pancreatic FNA for the diagnosis of malignancy was 64%, 100%, 100% and 16% respectively. CONCLUSIONS: EUS with FNA is useful for detection of malignancy in a pancreatic mass. The procedure appears to have a complication rate of 2%. Impact of this technique on clinical management of patients needs further evaluation.

Adenocarcinoma↗

Giant adrenal cyst: management and review of the literature.

The diagnosis of adrenal cysts is becoming increasingly more common with the widespread use of diagnostic imaging modalities. Most adrenal cysts are asymptomatic and less than 10 cm in diameter when discovered incidentally. Symptoms appear when adrenal cysts enlarge sufficiently to cause pain and gastrointestinal disturbances or become palpable. In this report, we present a case of a giant 45-cm right adrenal cyst manifesting as painless abdominal distention in a 23-year-old female. This case appears to be one of the largest adrenal cysts reported to date. The classification and management of adrenal cystic lesions is reviewed.

Adipose Tissue↗

Stereotactic core biopsy of the breast: results of one-year follow-up of 101 patients.

Stereotactic core biopsy (SCB) is being used as a cost-effective alternative to needle localized biopsy (NLB). However, an area of concern is the potential for sampling error, with sparse surgical data available concerning follow-up and failure rates. We therefore reviewed our results in patients undergoing SCB for mammographically detected breast abnormalities. Between January 1994 and February 1995, 128 patients underwent SCB. Average age was 56.4 years. Nine patients (7.0%) had histologic evidence of malignancy, with 111 (86.7%) benign diagnoses requiring no further initial intervention. Eight patients (6.3%) proceeded directly to NLB, five because of technical failure of SCB and three because of suspicious initial histology. One of the latter patients had ductal carcinoma in situ. The remaining 111 SCB patients were evaluated at 6 months and 1 year by mammographic and physical examination. Ten patients were lost to follow-up. Of the remaining 101 patients, 98 (97%) had stable mammograms and normal physical examinations. Three patients (3.9%) required subsequent NLB due to progression of the mammographic lesion. Two cases were histologically benign, and 1 patient had ductal carcinoma in situ adjacent to the previous SCB biopsy site. An additional patient underwent NLB for a new radiographic abnormality at a separate location in the ipsilateral breast, which was invasive ductal carcinoma. SCB appears to be an effective alternative to NLB for the majority of patients deemed eligible. Careful mammographic follow-up is warranted for these patients given the small, but real, possibility of sampling error.

Adult↗

Isolation of differentially expressed genes in carcinoma of the esophagus.

BACKGROUND: The genetic alterations that occur in the transformation of normal esophageal mucosa (NEM) to carcinoma of the esophagus (CAE) are not well understood. Differential display of mRNA is a recently described technique that uses reverse transcription and PCR to compare cDNA from paired normal and malignant tissue to determine whether there is either genetic loss (putative tumor suppressor gene) or overexpression (putative oncogene) in malignant cells. Our goal was to identify some of these genes from patients with CAE. METHODS: Specimens of NEM and corresponding CAE were obtained from patients at endoscopy or surgical resection and immediately snap frozen. Total RNA was isolated, reverse transcribed to cDNA, and PCR amplified with a predefined 10-mer oligonucleotide. The products were displayed on a polyacrylamide gel. Differential bands were isolated and sequenced and/or used as probes for Northern analysis. RESULTS: Application of the differential display method resulted in the isolation of 49 cDNA clones from three patients with CAE. Sequencing of the clones has revealed five unique sequences not previously reported and one that has been identified as histone H3.3. Northern analysis of histone H3.3 has revealed overexpression in four of six CAEs but not the paired NEM. In addition, whereas only 5 of 13 normal human cell lines of various origins overexpressed this gene, 11 of 12 human cancer cell lines (9 of 9 adenocarcinomas) overexpressed it. CONCLUSIONS: Differential display can be used to isolate potential oncogenes and tumor suppressor genes. We have identified five unique sequences and one known gene that may contribute to the development of CAE.

Adenocarcinoma↗

The surgical management of melanoma: from diagnosis to local treatment.

It is critical for physicians who may play a role in the diagnosis of melanoma to be knowledgeable of how to approach a suspicious nevus. A full thickness of tissue is necessary to microstage the melanoma and thereby guide subsequent treatment decisions. The past two decades have witnessed a dramatic change in the surgical management of this disease in that the margin of excision seems to be constantly shrinking. Well-conducted randomized studies have shown conclusively that narrower margins are sufficient for thin and intermediate thickness melanomas. Thus, the survival is comparable with that achieved for more radical excisions with less functional and cosmetic deficit.

Biopsy↗

Surgical management of patients with intermediate thickness melanoma: current role of elective lymph node dissection.

The appropriate role of elective hymph node dissection (ELND) in patients with clinical stage I intermediate thickness melanoma lesions remains a dilemma. Despite an impressive number of carefully performed nonrandomized/retrospective studies and two criticized multi-institutional prospective randomized trials, a clear benefit from ELND is still debatable. As a result, there currently is no standard approach for selecting patients who should undergo this procedure. Further prospective trials performed by the Intergroup/National Cancer Institute and World Health Organization (WHO) Melanoma groups, addressing Intermediate thickness extremity and truncal lesions respectively, have recently been completed. No long-term survival data is yet available from either group. Potentially conflicting preliminary results recently presented noted a significant ELND survival advantage for a subgroup of men with axial lesions in the Intergroup study, and no differential in survival demonstrable for the World Health Organization study at a median follow-up of 4 years. One area of agreement among surgeons on either side of the controversy is the need to be able to identify in a minimally invasive manner stage I-II melanoma patients with clinically occult lymph node metastases from the population at risk. Technologies such as polymerase chain reaction and lymphoscintigraphy to improve our ability to detect clinically occult lymph node metastases and facilitate the identification of sentinel node(s) for selective lymphadenectomy hold some promise. Although more research needs to be performed, these approaches potentially would allow for a more directed application of ELND in a much smaller number of melanoma patients. This could provide an entirely novel and more effective approach to the manner in which we evaluate patients with intermediate thickness melanoma lesions and would decrease the significance of this controversy. It is hoped that the long-term data about the appropriate role of ELND from the current prospective trials will provide definitive information on which to base decisions, or that current research will fundamentally alter our approach to these patients. In the interim, surgeons must continue to make their best judgments about the management of regional lymph nodes in an individual patient setting based on prior experience or personal bias.

DNA, Neoplasm↗

Low-affinity nerve growth factor receptor expression in sciatic nerve during P2-peptide induced experimental allergic neuritis.

Northern blot, immunocytochemistry, and single nerve fiber immunostaining were used to determine the expression of low-affinity nerve growth factor (NGF) receptor (p75NGFR) in the peripheral nervous system of Lewis rats during the course of experimental allergic neuritis (EAN) induced with 100 micrograms of 'SP26' synthetic peptide, corresponding to residues 53-78 of bovine P2 myelin protein. This severe reversible polyneuropathy, characterized by extensive multifocal demyelination in nerve roots, and axonal degeneration within sciatic nerve, represents a useful tool to investigate Schwann cell gene expression in these different pathological conditions. Our results showed that both p75NGFR mRNA and protein were induced within sciatic nerve by day 18 and 23 after 'SP26' immunization. By this time, however, p75NGFR was not detectable in roots of cauda equina. These data demonstrate that, during EAN induced by immunization with 100 micrograms of 'SP26', p75NGFR is up-regulated in Schwann cells and in nerve fibers distally along the nerve. This suggests that the induction of the receptor in sciatic nerve during P2-peptide EAN is related to the loss of axonal contact by Schwann cells.

Animals↗

Immediate vs. salvage resection after local treatment for early rectal cancer.

PURPOSE: There is an increasing awareness of local procedures to treat early stage rectal cancer. Abdominoperineal resection (APR) or low anterior resection (LAR) has been recommended if adverse pathologic findings are encountered in the local excision specimen. No data compare the impact on survival of "immediate" resection for adverse features vs. "salvage" resection for clinical recurrence. METHODS: We reviewed retrospectively 155 patients who underwent initial curative treatment of invasive rectal cancer by excision (91), snare-cautery (44), and fulguration (20). RESULTS: Twenty-one patients underwent APR/LAR immediately after initial local treatment, whereas another 21 patients underwent salvage APR/LAR for local recurrence. The disease-free survival after APR/LAR was 94.1 percent for the immediate group and 55.5 percent for the delayed group (P < 0.05). CONCLUSION: This decreased survival observed after delayed resection supports the recommendation for immediate APR/LAR when adverse pathologic features are present in the excision specimen.

Aged↗

Local surgical treatment of rectal cancer.

Patients with cancer of the lower third of the rectum can avoid both the morbidity of an APR and the need for a permanent colostomy by having the cancer removed by local excision. If the surgeon clinically suspects that a patient has an early cancer, the first step should be local excision of the tumor. The pathological features of the cancer specimen will then indicate the next step in treatment. This can range from no further therapy to proctectomy with or without an anastomosis (Table 2). Patients with a low risk of local failure can be treated by excision alone. Those with a higher risk of local failure should undergo APR or LAR or enter a protocol to determine the role of local excision and adjuvant chemoradiation.

Humans↗

The effect of benign breast biopsy on subsequent breast cancer detection practices.

PURPOSE/OBJECTIVES: To determine the effect of benign breast biopsy results on the frequency of subsequent breast self-examination (BSE), mammograms, and clinical examinations. DESIGN: Retrospective, descriptive design. SETTING: Two surgical oncology practices of an academic health science center in the southeastern United States and one surgical oncology practice and three family practices in another southern U.S. city. SAMPLE: A nonprobability sample consisting of 238 women with benign breast biopsies and a comparison group of 243 women with no histories of breast disease. METHODS: Questionnaires based on American Cancer Society (ACS) breast cancer detection guidelines were designed and mailed to all women who had benign breast biopsies within the past three years at the academic health science center. Similar questionnaires were mailed to women randomly selected from three family practices who had no histories of breast disease. Chi-square, Kruskal-Wallis one-way analysis of variance, and Wilcoxon matched pairs signed-ranks test were used in the data analysis. MAIN RESEARCH VARIABLES: Frequency of breast cancer detection practices including BSE, mammography, and clinical breast examinations. FINDINGS: In the group that had undergone biopsies, breast abnormalities were found by mammogram (38.8%), BSE (28.3%), clinical examination (16.9%), and accidental discovery (8.7%). The percentage of women performing monthly BSE increased from 47.4% to 67.3% postbiopsy (p < 0.0001). The frequency of mammography and clinical breast examinations also significantly increased postbiopsy (p < 0.0001). Similarly, the postbiopsy rate of BSE, mammography, and clinical breast examinations was higher than the rates for the control group. Women whose breast abnormalities were found by mammography became significantly more fearful of mammography (p < 0.05). CONCLUSIONS: Benign breast biopsies are associated with increased breast cancer detection practices. IMPLICATIONS FOR NURSING PRACTICE: All women need to follow ACS guidelines for breast cancer detection. Women who have undergone breast biopsy may be unduly afraid about the results of future detection practices and may need support and encouragement.

Adult↗