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Biomedical subjects

N Voravud

Publications and source records attributed to N Voravud.

48 records · Page 3Linked to original sources

Antineoplastic-associated colitis in Chulalongkorn University Hospital.

Clostridium difficile is well known for causing pseudomembranous colitis. Most cases are associated with the use of antimicrobial agents. Non-antibiotic associated colitis has rarely been reported. The causes of colitis are related to dietary changes, anesthesia, uremia, and various non-antibiotics medications, especially antineoplastic agents. Most responsible antineoplastics in previous reports are methotrexate and 5FU. From July 1993 to August 1994, 34 cancer patients developed acute diarrhea after chemotherapy. Six cases hd chemotherapy-associated colitis. All patients presented with moderate to severe diarrhea and demonstrable C.difficile toxin in fecal specimens and did not receive any antibiotics before the onset of diarrhea. Premier enzyme immunoassay (EIA) was used for toxin A assay because it is easy to perform and needs no special tissue culture laboratory facility. Data from multicenters studies have shown good sensitivity and specificity of the test. We found documented antineoplastics associated colitis, 7 episodes from 35 episodes of diarrhea (20.0%) that had been tested with EIA for toxin A. Five of 6 episodes were 5FU related. One patient had 2 episodes of antineoplastic associated colitis with the same chemotherapy regimen. The underlying malignancies were GI malignancies in 3 of 6 patients. In conclusion, moderate to severe diarrhea in cancer patients after chemotherapy should alert the physician to be aware of a potential fatal complication caused by C.difficile infection. True incidence has been undoubtedly masked by concomitant antimicrobial treatment and physician unawareness. Early recognition, discontinuation of chemotherapy and prompt treatment should be done to reduce morbidity and mortality of this disease.

Aged↗

Changes in white blood cells and myeloperoxidase activity in rhG-CSF prophylactic patients receiving cytotoxic chemotherapy.

The patterns of white blood cell parameters and mean peroxidase index (MPXI) changes in recombinant human granulocyte colony-stimulating factor (rhG-CSF) prophylactic patients, receiving myelosuppressive chemotherapy, have been studied in 8 cases, using flow cytochemistry blood autoanalyser (Technicon R H*1). No severe neutropenia (absolute neutrophil count, ANC < 0.50 x 10(9)/L) appeared in 6 rhG-CSF primary prophylactic patients, but severe neutropenia was noticed in 2 rhG-CSF secondary prophylactic patients for a period less than 1 week. In most of the cases the significant increase of neutrophil during leukocytosis occurred within 24 hours after starting rhG-CSF prophylaxis, and decreased within 24 hours after the end of rhG-CSF prophylaxis. There was a small degree of lymphocytosis, monocytosis, and basophilia in some cases. From this study, there were no significant changes of MPXI during rhG-CSF prophylaxis, the neutrophils produced during proliferative response to rhG-CSF possessed normal myeloperoxidase (MPO) activity. We concluded that the information obtained from automated blood cell analyser Technicon R H*1 especially MPXI and ANC, could be very useful for monitoring rhG-CSF prophylactic patients receiving myelosuppressive chemotherapy. The advantages of the MPXI over other methods is its simplification when performed as part of a routine complete blood count (CBC) on an automated hematology instrument, and its ability to measure even severe neutropenic samples.

Aged↗

Biosynthesis and processing of the platelet derived growth factor type alpha receptor.

The homodimers (AA, BB) of the platelet derived growth factor (PDGF) differentially interact with two highly related PDGF receptors (alpha, beta) that appear to mediate different functional responses in different cell types. To seek a basis for these apparent functional differences, we investigated the processing of the PDGF alpha-receptor. The PDGF alpha-receptor is rapidly glycosylated to a 160 kD form and undergoes a number of intermediate glycosylation steps that result in a mature form of 185 kD that appears at the cell surface within 60-90 minutes. The alpha receptor has a half-life of approximately 4 1/2 hours without and approximately 20 minutes in the presence of ligand. The processing steps of the alpha-receptor are similar to the processing of the PDGF beta receptor, suggesting that differential binding of signalling molecules to activated receptors may be responsible for the apparent functional differences in cellular responses to PDGF AA and PDGF BB.

3T3 Cells↗

Sequential increases in proliferating cell nuclear antigen expression in head and neck tumorigenesis: a potential biomarker.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a 36-kd nuclear protein whose expression is associated with DNA synthesis and cell proliferation. Tumorigenesis in head and neck squamous cell carcinoma is proposed to be a multistep process; dysregulation of proliferation is a potential marker of this process. PURPOSE: PCNA dysregulation was analyzed in squamous cell carcinoma tissue samples containing premalignant lesions (hyperplasia and/or dysplasia) and in adjacent normal epithelium to better understand proliferative changes during head and neck tumor development. METHODS: Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded sections by using a monoclonal anti-PCNA antibody. PCNA expression was analyzed in 33 head and neck squamous cell carcinomas and in their adjacent premalignant lesions from different sites and compared with that in the control samples, which had never been exposed to first-hand tobacco smoke. PCNA expression was assessed by semiquantitative scoring (scale 0-3) in three epithelial layers (basal, parabasal, and superficial). The labeling index and the weighted mean index of PCNA expression were calculated. RESULTS: Normal epithelium adjacent to the tumor had much more proliferative activity than the controls: The weighted mean index of PCNA expression was four-fold higher in the basal layer and sixfold higher in the parabasal layer. PCNA expression increased as tissues progressed from adjacent normal epithelium to hyperplasia (P < .001), hyperplasia to dysplasia (P < .001), and dysplasia to squamous cell carcinoma (P = .065); the total increase in PCNA expression ranged from fourfold to 10-fold from adjacent normal epithelium to squamous cell carcinoma. PCNA expression was higher in the parabasal than in the basal layer at all premalignant stages (23 of 25 samples in adjacent normal epithelium, 12 of 13 in hyperplasia, and 17 of 22 in dysplasia). As the tissue progressed from normal through premalignant stages to squamous cell carcinomas, we observed not only incremental increases in the labeling index, but also incremental increases in PCNA expression per labeled cells. CONCLUSIONS: These results indicate that PCNA could be a useful biomarker for multistep carcinogenesis in head and neck cancer and may serve as an intermediate end point in chemopreventive trials.

Antigens, Neoplasm↗

Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis.

Head and neck cancer development has been proposed to represent a multistage process characterized by dysregulation of proliferation and differentiation and driven by an accumulation of genetic alterations in an anatomic field repeatedly exposed to carcinogens. To visualize the accumulation of genetic alterations during head and neck tumorigeneses and to determine the extent of the genetically altered field, we probed 25 squamous cell carcinomas of the head and neck and their adjacent premalignant lesions for numerical chromosome aberrations by nonisotopic, in situ hybridization using chromosome-specific centromeric DNA probes for chromosomes 7 and 17. Normal control oral epithelium from individuals free of cancer showed no chromosome polysomy (i.e., cells with > or = 3 chromosome copies), whereas histologically normal epithelium adjacent to the tumors showed squamous cells with polysomies for chromosomes 7 and 17. Moreover, the frequency of cells with polysomy increased as the tissues passed from histologically normal epithelium to hyperplasia to dysplasia to cancer. The finding of genotypic abnormalities in histologically normal and precancerous regions adjacent to the tumor supports the concept of field cancerization. The finding of progressive genetic changes as the tumor develops supports the concept of multistep carcinogenesis in the head and neck region. Such genotypic parameters could serve as biomarkers in the assessment of the risk of progression to malignancy and as intermediate end points in chemoprevention trials.

Adult↗

Early genetic changes during upper aerodigestive tract tumorigenesis.

Upper aerodigestive tract tumorigenesis has been hypothesized to represent a field cancerization process with multistep events based on its association with known carcinogens, its frequent associated premalignant lesions, and its multifocal clinical manifestation. To further explore this working hypothesis, we have examined normal tissue and premalignant lesions in the field of tumors for evidence of genetic change. Paraffin sections of head and neck tumors harboring neighboring premalignant lesions were explored for the presence of chromosome polysomies using in situ hybridization and chromosome-specific centromeric probes. Cells exhibiting random polysomy were observed in the premalignant regions near the tumors. The frequency of polysomy in the tumor field increased as the tissue progressed from normal morphology (33%), to hyperplasia (67%), to dysplasia (95%), and to squamous cell carcinoma (96%). These results support the notions of field cancerization and multistep tumorigenesis in the aerodigestive tract. To determine whether the degree of accumulated genetic alterations might serve as a biomarker for risk of developing malignancy, a set of biopsies of oral premalignant lesions (leukoplakia, erythroplakia) were retrospectively chosen for polysomy analysis from two groups of individuals: one group who subsequently developed oral cancer and one group who did not develop oral cancer. Three of the five individuals who showed significant chromosome polysomies in their biopsies subsequently developed oral cancer, whereas only one of eight individuals with little evidence of polysomy subsequently progressed to oral cancer. These results suggest that evidence of generalized genetic change or instability might be useful as a genetic biomarker for risk assessment.

Digestive System Neoplasms↗

Phase II trial of 13-cis-retinoic acid plus interferon-alpha in recurrent head and neck cancer.

13-cis-retinoic acid (isotretinoin) and interferon-alpha have limited activity as single agents in advanced cancer. Preclinical data indicate that these agents have different mechanisms of action and, in combination have greater activity (that is, the ability to modulate growth and differentiation) in a number of malignant cell types than either agent alone. In clinical trials, the new biological regimen of 13-cis-retinoic acid and interferon-alpha was shown to have major activity in advanced squamous cell carcinoma of the skin and cervix. We conducted a phase II trial of this regimen in recurrent squamous cell carcinoma of the head and neck. Of the 21 evaluable patients, none had a complete response, and only one had a partial response (5%). Two patients had minor responses, four had stable disease, and 14 experienced disease progression. Five patients developed grade 3 toxic effects, including skin toxicity, fatigue, headache, and anorexia/weight loss. The median survival duration was 25.5 weeks (range, 4-95). The combination of 13-cis-retinoic acid and interferon-alpha at this dose and schedule is ineffective for the treatment of recurrent squamous cell carcinoma of the head and neck.

Adult↗

Vertebral osteomyelitis mimicking bone metastasis in breast cancer patients.

Vertebral osteomyelitis can be a diagnostic pitfall for physicians, since it is protean and often subtle in its clinical presentation. It can coexist with metastatic lesions or mimic vertebral bone metastasis. When it occurs in patients with breast cancer, who are prone to have bone metastasis, it can present perplexing diagnostic problems. Misdiagnosing vertebral osteomyelitis as bone metastasis or vice versa results in delayed diagnosis and inappropriate treatment and may cause serious morbidity. We emphasize this problem by presenting the cases of two patients with breast cancer whose clinical course was complicated by vertebral osteomyelitis. When the clinical course of breast cancer is different from this usual presentation, a different process should be suspected, and histologic diagnosis should be promptly sought. Fine-needle aspiration biopsy and culture of suspicious-appearing bony lesions is recommended as a rapid and reliable method of establishing a definite diagnosis in this circumstance.

Breast Neoplasms↗

Implantation metastasis of carcinoma after percutaneous fine-needle aspiration biopsy.

Implantation of malignant cells along the needle tract is an extremely rare but potential complication following percutaneous needle aspiration biopsy of malignant lesions. Percutaneous fine-needle aspiration biopsy (FNAB) has recently received more attention for cytologic diagnosis of bronchogenic carcinoma because of its high diagnostic yield, simplicity, and low morbidity. On the other hand, dissemination of cancer cells by needle aspiration biopsy can change a potentially resectable localized lung cancer to an unresectable one. We report two cases: one patient underwent FNAB of a metastatic left adrenal mass that seeded a paraspinal muscle implantation of malignant cells that subsequently developed a tumor mass, and the second patient had tumor cell implantation in the chest wall after FNAB of a pleural-based adenocarcinoma of the lung. The theoretical and practical importance of tumor cell spread along the needle tract is discussed. Because of its rare incidence, however, this complication should not affect the use of needle aspiration biopsy in bronchogenic carcinoma, although care should be undertaken during the procedure.

Adenocarcinoma↗

Breast cancer and second primary ovarian cancer in dermatomyositis.

We report six female patients with breast cancer who developed dermatomyositis and compare our data with those from other reports. The development of dermatomyositis in two patients led to the discovery of a second primary ovarian carcinoma, whereas the development of dermatomyositis in another two patients led to the discovery of recurrent breast cancer. In three patients the diagnosis of dermatomyositis preceded the diagnosis of breast cancer, while the rest developed dermatomyositis after the diagnosis of breast cancer. A parallel clinical course of dermatomyositis and breast cancer was seen in only one patient. Coexisting dermatomyositis and breast cancer is a rare phenomenon, and dermatomyositis that develops during the course of breast cancer may indicate the occurrence of a second primary malignancy or recurrent breast cancer. The onset of dermatomyositis may precede, coincide with, or follow the diagnosis of breast cancer. The clinical course of dermatomyositis sometimes, but not always, parallels the course of breast cancer. There are no specific clinical or laboratory markers to distinguish patients with dermatomyositis who have malignancy from those without cancer.

Adult↗

Oncogene expression in cholangiocarcinoma and in normal hepatic development.

The expression of the proteins encoded by the ras, myc, and erb B-2 oncogenes was examined in 63 paraffin-embedded human cholangiocarcinomas of Thai and English origin using immunohistochemistry. The observed distributions were compared with oncogene expression in a series of human hepatocellular carcinomas. In an attempt to relate expression of these three oncogenes to specific stages of normal tissue differentiation, tissue sections of normal fetal, infant, and adult human livers were also examined. Of 63 cholangiocarcinomas, 59 (95%) expressed p62 c-myc, 47 (75%) expressed p21 c-ras, and 46 (73%) expressed p190 c-erbB-2. The expression of c-myc and c-ras but not of c-erb B-2 correlated directly with tumor differentiation as judged by morphologic criteria. No difference was observed in oncogene expression between intrahepatic and extrahepatic cholangiocarcinomas. Twelve of 14 hepatocellular carcinomas (86%) stained positively for all three oncoproteins. During normal liver development, expression of c-myc and c-ras was shown to occur from 18 weeks' gestation until 5 years of age, but not thereafter. Expression of c-myc, c-ras, and c-erbB-2 oncogenes may be used as immunohistochemical markers to distinguish cholangiocarcinoma from nonneoplastic biliary tissues, and may provide useful information concerning the cell biology of tumor differentiation.

Adenoma, Bile Duct↗