Biomedical subjects

L K Lam

Publications and source records attributed to L K Lam.

At least 37 records · Page 2Linked to original sources

PubMed1996

Lymphoepithelioma-like carcinoma of the skin.

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Aged↗

PubMed1996

Primary closure of pharyngeal remnant after total laryngectomy and partial pharyngectomy: how much residual mucosa is sufficient?

After total laryngectomy with or without partial pharyngectomy, the remaining pharyngeal defect can be repaired either by primary closure or with additional tissue, depending on the amount of pharyngeal tissue remnant available. The aim of this study was to determine the minimum width of the pharyngeal remnant that could be safely closed primarily without causing difficulty in swallowing. A total of 52 consecutive patients who underwent total laryngectomy were entered into the study. The relaxed and stretched widths of the pharyngeal remnant were measured after removal of the specimen. The widths of the pharyngeal mucosa ranged from 1.5 to 5.0 cm relaxed (mean, 3.24 cm) and from 2.5 to 8.0 cm stretched (mean, 4.83 cm). All neopharynx was reconstructed by closing the pharynx primarily. Seven of the 52 patients developed recurrent tumor with concomitant dysphagia. Two of the 45 patients without recurrence presented with acute dysphagia from food bolus obstruction, and 1 patient developed benign inflammatory stricture following an episode of fish-bone impaction. The narrowest widths of the pharyngeal remnant in this group of 45 were 1.5 cm relaxed and 2.5 cm stretched. As these patients do not have swallowing difficulty, we conclude that in the absence of tumor recurrence, this amount of residual pharyngeal tissue is sufficient both for primary closure of the pharynx and in restoring swallowing function.

Adult↗

PubMed1995

Analysis of recurrence after surgical treatment of advanced laryngeal carcinoma.

The pattern of recurrences after surgical treatment of 276 patients with stage T3 and T4 laryngeal carcinoma was reviewed. Nodal recurrence was the commonest site and occurred mainly in patients with supraglottic and transglottic carcinoma. Distant metastasis was the second commonest site of recurrence, and the most distant metastases developed without locoregional recurrence. Local recurrence alone was uncommon in patients treated with primary surgery.

Adult↗

PubMed1995

Massive craniofacial osteolysis.

Involvement of the craniofacial skeleton by the process of massive osteolysis has been infrequently recorded. We describe a patient whose extent of craniomaxillofacial bony loss defied combined reconstruction by combined autogenous tissue and alloplastic materials. The clinical and radiographic features and management approaches to massive osteolysis are reviewed.

Adult↗

PubMed1994

Colonoscopic colostomy model in rats for colon tumorigenesis studies.

A colonoscopic colostomy model for colorectal carcinogenesis and chemoprevention was developed in F344 rats. The colon was transected at the middle of the transverse colon and sutured to two openings. The proximal opening, located on the middle line of the upper abdominal wall, was for the exit of feces. The distal one located on the left back was the colostomy for the lower part of colorectum, which was approximately 9 cm in length and isolated from the feces. The two openings of the colostomy were completely separated with at least 4 cm distance between them. The animals were treated with 1,2-dimethylhydrazine (DMH) or methylazoxymethanol acetate (MAMAc) systemically or topically. Colon tumors in the isolated colorectum were observed by colonoscopy. Twenty six tumors in the isolated colorectum were found by colonoscopy with a mean latent period of 25.6 weeks in 10/15 (66.6%) animals treated with DMH (30 mg/kg subcutaneously, weekly for 30 weeks). Twelve tumors were found by colonoscopy with a mean latent period of 32.8 weeks in 6/17 (35.3%) animals treated with MAMAc (5 mg/kg enema, weekly for 35 weeks). Tumors with 0.5 mm diameter were detected as early as 21 weeks following the first dose of DMH and 28 weeks following the first dose of MAMAc respectively. Video camera-assisted endoscopic examination detected suspected small tumors 6 weeks earlier than endoscopic evaluation alone. The number, size and location of the tumors observed by colonoscopy were significantly correlated with those observed at necropsy. The tumor growth rate was monitored weekly. The tumor growth curve was expressed as the mean tumor diameters and calculated tumor volumes. Histological study at necropsy showed that 48.1% of the tumors were adenomas and 51.9% were adenocarcinomas. With a complete fecal diversion and colonoscopy, the model is potentially useful to study colon carcinogenesis and the inhibition of colon carcinogenesis.

1,2-Dimethylhydrazine↗

PubMed1993

Regional chemotherapy for recurrent squamous head and neck cancers through a saphenous vein interposition graft.

Regional chemotherapy for head and neck cancers is effective, but the intra-arterial catheter is not without problems. We interposed a segment of saphenous vein within the carotid system to administer chemotherapeutic agents percutaneously via the arterialized venous segment. From 1983 to 1990, saphenous vein interposition graft was performed after radiotherapy in 24 patients with persistent or recurrent squamous head and neck cancers, which were also considered unresectable. There was no operative mortality. Two patients developed thrombosed vein graft; another two had wound infection; and one patient had a neck hematoma. Cisplatin was administered percutaneously every week via the saphenous vein graft. The response rate was 64% (complete response, 23%; partial response, 41%), and the 5-year actuarial survival rate was 31%. The 1-year survival rates for patients with complete, partial, and no response were 80%, 33%, and 13%, respectively. Saphenous vein interposition graft is a safe and convenient way of delivering intra-arterial chemotherapy, and it provides significant palliation for patients with recurrent nonresectable squamous head and neck cancers after radiotherapy.

Aged↗

PubMed1993

Associated injuries in facial fractures: review of 839 patients.

Patients with facial trauma may have associated injuries requiring immediate or specialised attention. This paper reports the incidence and nature of significant associated neurosurgical, ocular, spinal, torso and extremity injuries in facial fracture patients treated by the Department of Plastic and Reconstructive Surgery from June 1989 to June 1992. Of 839 patients treated during the period, 95 patients (11.3%) sustained significant concomitant injuries outside the facial skeleton. There were 45 (5.4%) patients with associated neurosurgical injuries, 33 (3.9%) with ocular injuries, 8 (0.9%) with spinal injuries, 16 (1.9%) with injuries of the torso, and 62 (7.4%) with injuries of the extremities. The spectrum of the injuries is presented. Most neurosurgical injuries are a result of focal impact and the intervention required is related mainly to local fracture management and the repair of dural tears. The risk of significant ocular injury is highest when the fracture involves the orbit. Injuries of the spine, torso (chest, abdomen, pelvis), and limbs were seen mainly in road trauma patients.

Abdominal Injuries↗

PubMed1993

Chemoprevention of benzo[a]pyrene-induced forestomach cancer in mice by natural phthalides from celery seed oil.

Bioassay-directed fractionation of celery seed oil from the plant Apium graveolens (Umbelliferae) led to the isolation of five natural products, including d-limonene, p-mentha-2,8-dien-1-ol, p-mentha-8(9)-en-1,2-diol, 3-n-butyl phthalide, and sedanolide. Of these compounds p-mentha-2,8-dien-1-ol,3-n-butyl phthalide, and sedanolide exhibited high activities to induce the detoxifying enzyme glutathione S-transferase (GST) in the target tissues of female A/J mice. 3-n-Butyl phthalide and sedanolide (20 mg/dose every two days for a total of 3 doses) increased GST activity 4.5-5.9 and 3.2-5.2 times over the controls in the mouse liver and small intestinal mucosa, respectively. At the same dose, p-mentha-2,8-dien-1-ol induced GST activity about 3.7-fold above that of the controls. Thus, these compounds were further tested for their ability to inhibit benzo[a]pyrene- (BP) induced tumorigenesis in mice. After treatment with 3-n-butyl phthalide and sedanolide, the tumor incidence was reduced from 68% to 30% and 11%, respectively. About 67% and 83% reduction in tumor multiplicity was also observed with 3-n-butyl phthalide and sedanolide. p-Mentha-2,8-dien-1-ol produced only a small or no significant reduction of forestomach tumor formation. The data indicating that 3-n-butyl phthalide and sedanolide were both active in tumor inhibition and GST assays suggested a correlation between the inhibitory activity and the GST-inducing ability. The phthalides are known to determine the characteristic odor of celery. The results suggest that phthalides, as a class of bioactive natural products occurring in edible umbelliferous plants, may be effective chemopreventive agents.

Animals↗

PubMed1992

Isolation and biological evaluation of potential cancer chemopreventive agents from ambrette musk residue.

Two nitroaromatic compounds, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4-dinitrobenzene (1) and 1-[4-(1,1-dimethylethyl)-2,6-dimethyl-3,5-dinitrophenyl]ethanone or musk ketone (2), were isolated from ambrette musk residue, which is widely used in the food and cosmetics industry. The ability of 1 and 2 to induce increased activity of the detoxifying enzyme glutathione S-transferase was tested in A/J mice. Enzyme induction in the cytosols of liver, forestomach, lung, colon, and small intestinal mucosa was determined. Biological evaluation revealed that both compounds exhibit high activity as glutathione S-transferase inducers in liver and small intestinal mucosa. The effects of 1 and 2 on the levels of acid-soluble sulfhydryl in the five mouse tissues were also determined. Both compounds slightly elevated sulfhydryl levels in the small intestinal mucosa but significantly decreased the sulfhydryl levels in the other tissues. Because the ability of anticarcinogenic compounds to induce an increase in the detoxifying enzyme activity correlates with their tumor inhibitory activity, 1 and 2 may be potential cancer chemopreventive agents.

Animals↗

PubMed1992

Phenylalkyl isothiocyanate-cysteine conjugates as glutathione S-transferase stimulating agents.

To develop analogues of phenylalkyl isothiocyanate with less toxicity and better biological activity, two water-soluble phenylalkyl isothiocyanate-cysteine conjugates, S-[N-benzyl(thiocarbamoyl)]-L-cysteine (1) and S-[N-(3-phenylpropyl)(thiocarbamoyl)]-L-cysteine (2), were synthesized. The induction of increased activity of the detoxifying enzyme glutathione S-transferase by the conjugates and their parent compounds was determined and compared in several tissues of A/J mice. The biological evaluation revealed that the conjugates as GST enzyme inducers appeared to be less toxic and even more potent than the parent compounds in the mouse bladder. Compounds 1 was much more active than 2 in all the tissues examined, while their parent compounds showed an inverse order of activity. Thus, an increase in the alkyl chain length of the parent isothiocyanates or a decrease in the alkyl length of the conjugates could result in higher enzyme-inducing activity in the same compound series. Since a number of nitrosamines have been identified as prime bladder carcinogens and phenylalkyl isothiocyanates have been reported to inhibit a wide range of carcinogenic nitrosamines, the corresponding conjugates may serve as prodrugs to protect against nitrosamine-induced urinary bladder carcinogenesis once they are delivered to the target organ.

Animals↗

PubMed1992

Sesquiterpenes from clove (Eugenia caryophyllata) as potential anticarcinogenic agents.

Bioassay-directed fractionation of clove terpenes from the plant Eugenia caryophyllata has led to the isolation of the following five active known compounds: beta-caryophyllene [1], beta-caryophyllene oxide [2], alpha-humulene [3], alpha-humulene epoxide I [4], and eugenol [5]. Their structures were determined on the basis of spectral analysis (hreims, 1H and 13C nmr). These compounds showed significant activity as inducers of the detoxifying enzyme glutathione S-transferase in the mouse liver and small intestine. The ability of natural anticarcinogens to induce detoxifying enzymes has been found to correlate with their activity in the inhibition of chemical carcinogenesis. Thus, these sesquiterpenes show promise as potential anticarcinogenic agents.

Animals↗

PubMed1992

Anethofuran, carvone, and limonene: potential cancer chemopreventive agents from dill weed oil and caraway oil.

Bioassay-directed fractionation of dill weed oil and caraway oil, respectively, from the plants Anethum graveolens L. and Carum carvi L. (Umbelliferae) has led to the isolation of three monoterpenes, anethofuran (1), carvone (2), and limonene (3). Their structures were determined on the basis of spectral analysis. These compounds induced the detoxifying enzyme glutathione S-transferase in several mouse target tissues. The alpha,beta-unsaturated ketone system in carvone appeared to be critical for the high enzyme-inducing activity.

Animals↗

PubMed1992

Inhibition of hamster buccal pouch carcinogenesis by limonin 17-beta-D-glucopyranoside.

Limonin 17-beta-D-glucopyranoside, nomilin 17-beta-D-glucopyranoside, and nomilinic acid 17-beta-D-glucopyranoside, three limonoid glucosides isolated from oranges, were tested for cancer chemopreventive activity. Eighty female Syrian hamsters were divided into four equal groups. The left buccal pouches of the animals in each group were pretreated topically with two applications of water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside (Group III), or nomilinic acid 17-beta-D-glucopyranoside (Group IV). After this initial treatment, the left buccal pouches of 16 hamsters from each group were painted five times per week. Two or three times per week the pouches were treated with a 0.5% solution of the carcinogen 7,12-di-methylbenz[a]anthracene (DMBA) dissolved in mineral oil. On alternate days, the pouches were treated with water (Group I) or a 3.5% solution of limonin 17-beta-D-glucopyranoside (Group II), nomilin 17-beta-D-glucopyranoside, or nomilinic acid 17-beta-D-glucopyranoside. The 16 remaining animals were used as controls. These hamsters were treated five times per week, one day with mineral oil and the next with either water (Group I) or one of the 3.5% solutions of the limonoid glucosides (Groups II-IV). After 15 weeks (71 applications), the hamsters were killed. Multiple tumors were common in the animals treated with DMBA; however, the animals treated with limonin 17-beta-D-glucopyranoside exhibited a 55% decrease in average tumor burden. Further comparisons between Groups I and II showed that this reduction in tumor burden was mainly due to a decrease in tumor mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Inhibitory effects of 2-n-heptylfuran and 2-n-butylthiophene on benzo[a]pyrene-induced lung and forestomach tumorigenesis in A/J mice.

Many furan-containing natural products that induce increased activity of the glutathione S-transferase (GST) enzyme system have been found to inhibit tumorigenesis in laboratory animals. 2-n-Heptylfuran (HF) and 2-n-butylthiophene (BT), a sulfur analogue of furan, are two of the many furans and thiophenes formed during the roasting process of meat. BT and HF, when administered by gavage at doses that ranged from 11 to 90 mumol, induced increased GST activity in various tissues of A/J mice. At 90 mumol/dose, BT induced increased GST in the liver, small bowel mucosa, and lung. No increase in enzyme activity was found in the forestomach. HF was an enzyme inducer in the liver, small bowel mucosa, and forestomach but was inactive in the lung. The acid-soluble sulfhydryl level, a good measure of glutathione contents in tissues, was examined in tissue homogenates from mice treated with BT and HF. BT induced significant increase of GSH in the liver and lung at the higher doses. No change was observed in either the small bowel mucosa or the forestomach. A 50-mumol dose of HF was found to increase GSH level in all four tissues studied. The inhibition of lung and forestomach tumorigenesis was carried out with A/J mice using benzo[a]pyrene as the carcinogen. BT treatment resulted in a reduction of tumor multiplicity in the lung and forestomach. The tumor incidence in the forestomach was reduced significantly. The potency of HF as inhibitor of carcinogenesis was similar to that of BT in the forestomach of mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Inhibition of benzo[a]pyrene-induced tumorigenesis by myristicin, a volatile aroma constituent of parsley leaf oil.

Glutathione S-transferase (GST) assay-guided fractionation of parsley leaf oil from the edible plant Petroselinum sativum Hoffm. (Umbelliferae) led to the isolation of myristicin. Myristicin showed high activity as an inducer of the detoxifying enzyme GST in the liver and small intestinal mucosa of female A/J mice. Reduction of myristicin yielded dihydromyristicin that retained the GST-inducing activity. Myristicin and dihydromyristicin were tested for their capacity to inhibit benzo[a]pyrene (B[a]P)-induced tumor formation in female A/J mice. A 65% inhibition of the tumor multiplicity in the lung was observed as the result of treatment of myristicin. Dihydromyristicin produced small or insignificant reduction of lung tumor formation. In the forestomach, myristicin showed a 31% inhibition of tumor formation; while dihydromyristicin exhibited a 27% inhibition. Comparison of the structures and activities indicated that the saturation of the isolated double bond in myristicin resulted in a significant decrease in the inhibitory activity against B[a]P-induced tumorigenesis. The present results showed that myristicin, an active inducer of GST activity, is an effective inhibitor of B[a]P-induced tumorigenesis in mice. Stimulation of GST activity by myristicin could be a major mechanism for its inhibition of B[a]P or other carcinogens that may be detoxified in the same manner. As a culinary herb parsley is regularly consumed by humans. Parsley leaf oil is also used extensively for garnishing and seasoning. The results of this study indicate that as a major volatile aroma constituent of parsley myristicin may be an effective cancer chemopreventive agent.

Allylbenzene Derivatives↗

PubMed1991

Inhibition of cytoplasmic aspartate aminotransferase from porcine heart by R and S isomers of aminooxysuccinate and hydrazinosuccinate.

D- and L-aminooxysuccinate were synthesized and evaluated as inhibitors of cytoplasmic aspartate aminotransferase (EC 2.6.1.1) from porcine heart. L-Aminooxysuccinate was shown to be a slow binding inhibitor of the pyridoxal phosphate form of the enzyme with a Ki of 160 nM and a half-life of the inhibited complex of 8 min. Kinetic analysis revealed that inhibition followed a two-step mechanism in which the last step was rate-limiting. D-Aminooxysuccinate was not inhibitory up to a concentration of 0.1 mM. These compounds were compared to D- and L-hydrazinosuccinate, which are potent slow binding inhibitors of aspartate aminotransferase with Ki values of 1.5 and 0.5 nM, respectively. Models of all four analogs were built into the active site of the closed form of the enzyme. The energy-minimized conformations of both L-isomers bound to aspartate aminotransferase show better geometry for hydrogen bond and ion pair formation than do the corresponding D-isomers. The aldimine double bond formed by the L-isomers is not coplanar with the pyridoxal phosphate ring in accordance with the spectral properties of the inhibitor complexes that are characterized by broad absorbance bands. This lack of planarity was not evident for the models of D-hydrazinosuccinate and D-aminooxysuccinate.

Animals↗

PubMed1991

Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents.

Carcinogen-induced aberrant crypts (AC) of the colon are a precancerous state that leads to malignancy. The inhibition of AC formation by chemopreventive agents was evaluated in this study. Colon AC were induced by 1,2-dimethylhydrazine (DMH) in 3 weeks in CF1 mice. The cecum of the large intestine of CF1 mice did not produce more than one AC focus per animal. The effect of DMH and that of the inhibitors in this part of the large bowel were essentially similar to the vehicle control and inhibitor-only controls. The response of DMH treatment in the colorectal portion of the large bowel was found to be different from that of the cecum. The DMH treated mice had 13-17 foci per animal in three different experiments. The average number of AC per focus was greater than one in all three experiments performed. None of the inhibitor-only control animals nor the cottonseed oil vehicle control animals developed AC focus in the colorectal or the cecal part of the large bowel. The known inhibitor of colon carcinogenesis 3-butyl-4-hydroxyanisole reduced DMH-induced average AC formation by 10 and 46% at 1 and 4 mg per dose, respectively. The inhibitors 2-n-butylthiophene and phenylpropylisothiocyanate reduced DMH-induced average AC formation greater than 34 and greater than 40% respectively. The postulated inhibitor 2-n-octylthiophene, which is an eight-carbon homolog of 2-n-butylthiophene, similarly reduced DMH-induced AC formation. The known colon carcinogenesis inhibitor dehydroepiandrosterone, in contrast, has no effect. The inactivity of dehydroepiandrosterone to inhibit colon AC formation was attributed to its mechanism of inhibitory action, which differs from that of the phenol, isothiocyanate and thiophenes. The short duration that is required to produce quantifiable results suggests that the reduction of carcinogen-induced AC formation may be developed into a useful prescreening assay for potential chemopreventive agents against colon cancer.

1,2-Dimethylhydrazine↗

PubMed1991

Tumorigenicity of di-tert-butyl-substituted hydroquinone and hydroxyanisoles in the forestomach of Syrian golden hamsters.

The di-tert-butyl-substituted hydroxyanisoles 2,5-di-tert-butyl-4-hydroxyanisole (2,5-DTBHA) and 3,5-di-tert-butyl-4-hydroxyanisole (3,5-DTBHA) are contaminants of the commercial antioxidant butylated hydroxyanisole. The tumorigenicity of 2,5-DTBHA, 3,5-DTBHA, 2,5-di-tert-butyl hydroquinone (2,5-DTBHQ), a demethylated analog of 2,5-DTBHA, and 3-tert-butyl-4-hydroxyanisole (3-BHA) were investigated. Dietary 3-BHA, which has been shown previously to induce neoplastic lesions in the hamster forestomach, was found to cause the development of forestomach papilloma in 75% of the hamsters in 24 weeks at 1% addition to the diet. General thickening of the forestomach lining with moderate to severe hyperkeratosis and hyperplasia were observed in 14 (88%) of the 16 hamsters in this group. Inflammation was generally found in the forestomach of these animals. Similar observations were found in 14 (88%) of the 16 hamsters in the group that was fed 1% DTBHQ. Severe hyperplasia and papilloma found in the forestomach of these hamsters were similar in severity to those in the 3-BHA group. Unlike the 3-BHA and 2,5-DTBHQ groups, the forestomachs of 1% 2,5-DTBHA and 3,5-DTBHA treated animals were not different from the hamsters in the control group. Only mild hyperplasia at or near the limiting ridge was found in the forestomach of some of these animals. Hyperkeratosis or inflammation were not observed. Steric factors may play a role in the lack of tumorigenicity of 2,5-DTBHA and 3,5-DTBHA, while the formation of a stable free radical from 2,5-DTBHQ may be the activated species responsible for its tumorigenicity.

Animals↗