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Biomedical subjects

R Karl

Publications and source records attributed to R Karl.

12 recordsLinked to original sources
PubMed1999

Activating SRC mutation in a subset of advanced human colon cancers.

The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

3T3 Cells↗
PubMed1999

Surgical Approaches to Esophageal Cancer.

BACKGROUND: Esophageal cancer is a highly lethal malignancy. Esophageal resection remains the primary treatment in most centers. A number of approaches to esophageal resection have been described. METHODS: The authors review the current approaches to esophageal resection and adjuvant therapy for esophageal cancer. RESULTS: Transthoracic, transhiatal, and minimally invasive techniques are currently employed in esophageal surgery for malignancy. A number of authors favor extended mediastinal and cervical lymphadenectomy in hopes of improving survival. Combined chemotherapy and radiotherapy in the neoadjuvant setting appears to offer some promise. CONCLUSIONS: No consensus of opinion exists regarding the optimal approach or extent of esophageal resection for cancer. Prospective, randomized trials of neoadjuvant therapy may determine its efficacy. Newer approaches may enhance quality of life.

Journal Article↗
PubMed1998

Squamous-cell carcinoma of the pelvis in a giant condyloma acuminatum: use of neoadjuvant chemoradiation and surgical resection: report of a case.

A 60-year-old bisexual male was referred to our institution for management of an unresectable squamous-cell carcinoma of the pelvis arising in a giant condyloma acuminatum. He received neoadjuvant chemoradiation consisting of 5-fluorouracil and mitomycin C with concurrent external beam radiation, followed by posterior pelvic exenteration. The surgical specimen had no residual cancer. In situ hybridization was performed using a human papilloma virus omniprobe for human papilloma virus subtypes 6, 11, 16, 18, 31, 33, and 35. Two years after diagnosis the patient is doing well with no evidence of recurrent disease.

Antibiotics, Antineoplastic↗
PubMed1998

CD44V6 expression in human colorectal carcinoma.

CD44 is an adhesion molecule involved in cell-to-cell and cell-to-matrix interactions. This transmembrane glycoprotein exists in either standard or variant forms, originated by alternative splicing. One of the isoforms (CD44V6) has been shown, in some systems, to modify the metastatic potential of tumor cells. To investigate the role of this biomarker as possible prognostic antigen in colorectal cancer, we immunohistochemically analyzed the distribution of CD44V6 expression on formalin-fixed, paraffin-embedded tissues from resected colorectal cancers of 34 patients. The monoclonal antibody VFF7 against the amino acid sequence encoded by exon CD44V6 was applied using the avidin-biotin-peroxidase method. For each resected specimen, normal (N), adenomatous (AD), and carcinomatous (CA) colonic mucosa were tested. In 68% of the resected cases, these areas were present in the same slide, and in 76% of cases, nodal or liver metastases (MT) were available for evaluation. Adenomatous polyp biopsy specimens of 10 carcinoma-free patients were also tested. In selected cases, CD44V6 expression was also determined using the Western blot immunoprecipitation technique. CD44V6 immunoreactivity was detected in 100% of the ADs, and in 91% of CAs, but was mostly weak in only 38% of MTs (n=26). In 49% (n=35) of ADs, 11% (n=34) of CAs, and 4% of MTs (n=26), the stain was moderate to strong. CD44V6 immunoreactivity was predominantly membranous in ADs and cytoplasmic in MTs. In the CAs, both staining patterns were noted. Interestingly, the normal mucosa had a weak subnuclear localization of the stain. In the cases evaluated by Western blotting immunoprecipitation analysis, the level of CD44V6 protein expression was similar to that obtained by immunohistochemistry. No correlation was found with tumor type, stage, or patient survival. The predominant CD44V6 expression in ADs and CAs, but not in MTs, suggests that, in many cases, the expression of this adhesion molecule may be lost during the acquisition of migratory function by the tumor cells.

Adenocarcinoma↗
PubMed1998

Elevated c-Src protein expression is an early event in colonic neoplasia.

The molecular events regulating the development and progression of colonic neoplasia are currently being delineated. Recent studies have implicated c-Src protein kinase activation as an early event in the malignant transformation of colonic epithelial cells. However, increased c-Src activity has also been reported in colon carcinomas as well as in metastatic hepatic and extrahepatic colon carcinomas. To further investigate the potential role of c-Src in the progression of colonic neoplasia, we analyzed c-Src levels by immunohistochemistry in 27 colorectal resection specimens. Mouse monoclonal antibody to c-Src protein was applied to 3-micron sections from formalin-fixed, paraffin-embedded tissues using the avidin-biotin-peroxidase method. The combination of adenomatous (AD) and adjacent carcinomatous mucosa (CA) specimens were present in 20 of 27 patients. In 15 cases, synchronous metastatic (MT) lesions were available for evaluation. Strong c-Src expression was evident in 95% of AD (n = 20), in contradistinction to 32% of MT (n = 19) and 14% of CA (n = 22). Weak-to-moderate c-Src expression was seen in adjacent normal colonic mucosa (NM) in 96% of cases. Signed rank test univariate analysis revealed a statistically significant difference in c-Src expression between NM/AD (p = 0.0001), NM/CA (p = 0.0001), NM/MT (p = 0.0006), AD/CA (p = 0.0001), and AD/MT (p = 0.0002). No significant correlation between levels of c-Src expression and patient survival, tumor size, histologic grade, or tumor configuration was observed using the Cox's Regression Model. Similar results were obtained by analysis of c-Src protein levels and c-Src kinase activity as measured by Western blot and in vitro kinase assays of representative cases. Our results indicate that: (a) elevated c-Src expression is an important early event during colorectal carcinogenesis; (b) its activation may be involved in tumor progression in a subset of colonic carcinomas; and (c) additional molecular events are necessary for invasion to occur.

Adult↗
PubMed1994

Characteristics of prostatic infarcts and their effect on serum prostate-specific antigen and prostatic acid phosphatase.

OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.

Acid Phosphatase↗
PubMed1994

Management of Cancer in the Older Aged Person.

The management of cancer in the older person is an increasingly common aspect of oncologic practice. The central questions concern effectiveness and safety of antineoplastic therapy, clinical criteria to identify patients who may benefit from treatment, and individualized management plans. To address these questions, we review the influence of age on various forms of cancer treatment, explore the basis of treatment-related decisions in older persons with cancer, and propose areas for future investigation. Age itself is not a contraindication to cancer treatment. Individualized treatment plans, based on appropriate diagnosis, staging and comprehensive geriatric assessment, are most beneficial to the older patients.

Journal Article↗
PubMed1993

Chronic pressure ulcer carcinomas.

Carcinomas arising from chronic pressure ulcers, Marjolin's ulcers, are an uncommon occurrence. They are virulent cancers that require aggressive surgical treatment. We present 3 such cancers including the first report of a squamous cell carcinoma arising in a distal extremity pressure ulcer. Carcinomas arising in chronic pressure ulcers behave more aggressively than other types of Marjolin's ulcers and, therefore, they need to be treated more aggressively. Extensive surgical excisions with wide surgical margins are necessary and elective lymph node dissections should be considered for optimal therapy.

Adult↗
PubMed1987

[Building blocks for oligonucleotide syntheses with uniformly fragmentable beta-halogenated protective groups].

5'-Dimethoxytrityl-3'-phosphite amides of deoxynucleosides are synthesized. Phosphite/phosphate is protected by the 2,2,2-trichloro-1,1-dimethyl-ethyl (TCB) group, heterocyclic bases by the 2,2,2-trichloro-2,2-dimethyl-ethoxycarbonyl (TCBOC) group. Deoxyguanosine is also blocked by 6-O-trichloroethyl thus avoiding the difficulties observed with monoprotected guanine residues.

Deoxyribonucleosides↗
PubMed1985

[Comparison between cimetidine-pirenzepine and antacids for the prevention of stress hemorrhage in intensive care patients. A controlled clinical study on 125 patients].

In a controlled clinical trial, the efficacy of an intravenous combination of cimetidine and pirenzepine (group A: 62 patients) was compared with that of an intragastric administration of a magnesium-aluminium-hydroxide concentrate (group B: 58 patients) in preventing visible and occult upper gastrointestinal tract bleeding in intensive-care patients. It was found that both forms of therapy had the same favourable effect on the extent and incidence rate of visible and occult gastric bleeding. The antacid was more effective than the cimetidine-pirenzepine combination in raising the pH level to 4 or higher (P less than 0.05). Intensive-care patients should, therefore, be treated with the antacid whenever possible, since it is equally effective as the cimetidine-pirenzepine combination in preventing bleeding from the upper gastrointestinal tract, whereas it is superior in elevating the gastric pH. Besides, the use of the antacid is also less costly.

Adult↗
PubMed1981

Surgical implications of antithrombin III deficiency.

Antithrombin III is a potent coagulant inhibitor in plasma. Congenital deficiency of antithrombin III may predispose to thrombotic events and may complicate surgical management. We describe a patient with congenital antithrombin III deficiency who developed superior mesenteric vein thrombosis after the cessation of warfarin therapy which resulted in venous gangrene of the small intestine. Initial treatment of this deficiency with fresh frozen plasma and subsequent long-term management with warfarin therapy has been effective in avoiding further thrombotic events.

Adult↗