PubMed HealthSearch

Biomedical subjects

A Y Cheung

Publications and source records attributed to A Y Cheung.

At least 19 recordsLinked to original sources

Locally advanced head and neck cancer: combined chemotherapy and radical radiation therapy for organ and function preservation (interim report).

PURPOSE: This phase II study was performed to assess the feasibility of organ preservation after combined chemotherapy and radical radiation therapy in patients with resectable, locally advanced head and neck cancer. MATERIALS AND METHODS: Twenty-four patients had surgically resectable stage III (n = 9) and stage IV (n = 15) squamous cell carcinoma of the head and neck. Initially, they received two to three courses of neoadjuvant chemotherapy (5-fluorouracil and cisplatin). Patients in whom response was seen were then treated definitively with two courses of cisplatin chemotherapy administered concomitantly with radical radiation therapy. Patients in whom no response was seen underwent salvage surgery or other standard therapy. RESULTS: The response rate after induction chemotherapy was 84% (including 42% complete remission). Complete remission after concomitant chemotherapy and radical radiation therapy was 83%. After a median follow-up of 18 months (maximum, 3.5 years), 18 patients (75%) remained recurrence free. Grade 3 or 4 treatment-related toxicity was experienced, but there was no treatment-related mortality. CONCLUSION: Combined chemotherapy and radical radiation therapy used in this study resulted in organ and function preservation in the majority of patients with resectable stage III and IV head and neck cancer.

Adult

Organ-specific and Agamous-regulated expression and glycosylation of a pollen tube growth-promoting protein.

Transmitting tissue-specific (TTS) protein is a pollen tube growth-promoting and attracting glycoprotein located in the stylar transmitting tissue extracellular matrix of the pistil of tobacco. The TTS protein backbones have a deduced molecular mass of about 28 kDa, whereas the glycosylated stylar TTS proteins have apparent molecular masses ranging between 50 and 100 kDa. TTS mRNAs and proteins are ectopically produced in transgenic tobacco plants that express either a cauliflower mosaic virus (CaMV) 35S promoter-TTS2 transgene or a CaMV 35S-promoter-NAG1 (NAG1 = Nicotiana tabacum Agamous gene) transgene. However, the patterns of TTS mRNA and protein accumulation and the quality of the TTS proteins produced are different in these two types of transgenic plants. In 35S-TTS transgenic plants, TTS mRNAs and proteins accumulate constitutively in vegetative and floral tissues. However, the ectopically expressed TTS proteins in these transgenic plants accumulate as underglycosylated protein species with apparent molecular masses between 30 and 50 kDa. This indicates that the capacity to produce highly glycosylated TTS proteins is restricted to the stylar transmitting tissue. In 35S-NAG transgenic plants, NAG1 mRNAs accumulate constitutively in vegetative and floral tissues, and TTS mRNAs are induced in the sepals of these plants. Moreover, highly glycosylated TTS proteins in the 50- to 100-kDa molecular mass range accumulate in the sepals of these transgenic, 35S-NAG plants. These results show that the tobacco NAGI gene, together with other yet unidentified regulatory factors, control the expression of TTS genes and the cellular capacity to glycosylate TTS proteins, which are normally expressed very late in the pistil developmental pathway and function in the final stage of floral development. The sepals in the transgenic 35S-NAG plants also support efficient pollen germination and tube growth, similar to what normally occurs in the pistil, and this ability correlates with the accumulation of the highest levels of the 50- to 100-kDa glycosylated TTS proteins.

Caulimovirus

Prevalence and prognostic significance of tumor-associated tissue eosinophilia in nasopharyngeal carcinoma.

BACKGROUND: Tumor-associated tissue eosinophilia (TATE) has been associated with an improved prognosis in a variety of neoplasms. METHODS: Diagnostic biopsy specimens from 96 patients with nasopharyngeal carcinoma (NPC) were reviewed for the presence of TATE by an observer blinded to the patients' clinical histories. Comparisons between patients with and without TATE with respect to the probabilities of local recurrence, distant metastasis, and survival were performed using the log rank test on Kaplan-Meier product-limit estimates and the Cox proportional hazards model. RESULTS: The prevalence of TATE in these patients was 32%, and was not significantly associated with local recurrence, distant metastasis, or survival. CONCLUSIONS: These results are discordant with those of studies in other tumor models, although comparison is hampered by varying definitions of TATE. The differing results may be due to variations in the degree of activation of the eosinophils present in TATE in different tumors.

Carcinoma

Pollination induces mRNA poly(A) tail-shortening and cell deterioration in flower transmitting tissue.

Pollination induces many physiological responses in the flower, including deterioration and death in specific pistil cell types. It is shown here that within the style of tobacco, pollination-induced cell deterioration was restricted to the transmitting tissue while the surrounding cortical tissue was not affected. It was distinct from general senescence since exogenously applying the senescence-inducing hormone ethylene, or its precursor aminocyclopropane-1-carboxylic acid (ACC), to the flower or the pistil induced overall deterioration in the entire flower. Furthermore, both pollen tube growth and ethylene action were needed for the entire spectrum of cellular changes associated with this pollination-induced transmitting tissue deterioration process. It is also shown that pollination-induced mRNA poly(A) tail-shortening for at least three major classes of transmitting tissue-specific mRNAs. As is commonly observed for poly(A) tail-shortened mRNAs, the levels of two of these three mRNA classes decline after pollination. On the other hand, the third class of mRNAs, transmitting tissue-specific (TTS) mRNAs, was maintained at a very high level subsequent to pollination, even after substantial poly(A)-tail shortening. TTS mRNAs encode a pollen tube growth-promoting and -attracting protein needed for optimal in vivo pollen tube growth. The specific preservation of TTS mRNAs in the deteriorating transmitting tissue cells suggests that these cells can distinguish molecules needed in the pollinated styles from those that are dispensable, and protect them from degradation. It is suggested that the pollination-induced mRNA poly(A) tail-shortening and cell death are programmed processes suited to the post-pollination transmitting tissue environment. Results showing that ACC is a candidate signal molecule for the pollination-induced mRNA-shortening which is accentuated by ethylene and mediated via a protein phosphorylation-dependent signal transduction pathway are also presented.

Amino Acids

A floral transmitting tissue-specific glycoprotein attracts pollen tubes and stimulates their growth.

Pollen tubes elongate directionally in the extracellular matrix of pistil tissues to transport the male gametes from the apically located stigma to the basally located ovary for fertilization. The molecular mechanisms underlying directional pollen tube growth in the pistil are poorly understood. We have purified a glycoprotein, TTS, from tobacco stylar transmitting tissue, which supports pollen tube growth between the stigma and the ovary. TTS proteins belong to the arabinogalactan protein family, and they polymerize readily in vitro in a head-to-tail fashion into oligomeric forms. TTS proteins stimulate pollen tube growth in vitro and attract pollen tubes grown in a semi-in vivo culture system. In vivo, the pollen tube growth rate is reduced in transgenic plants that have significantly reduced levels of TTS proteins as a result of either antisense suppression or sense cosuppression. These results identify TTS protein as a pistil component that positively contributes to pollen tube growth.

Cell Division

A pollen tube growth stimulatory glycoprotein is deglycosylated by pollen tubes and displays a glycosylation gradient in the flower.

In plant sexual reproduction, pollen tubes elongate from the stigma, through the stylar transmitting tissue, to the ovary of the pistil to deliver the male gametes for fertilization. TTS protein is a tobacco transmitting tissue glycoprotein shown to attract pollen tubes and promote their growth. Here, we show TTS proteins adhere to the pollen tube surface and tips, suggesting that they may serve as adhesive substrates for pollen tube growth. TTS proteins are also incorporated into pollen tube walls and are deglycosylated by pollen tubes, suggesting that they may provide nutrients to this process. Within the transmitting tissue, TTS proteins display a gradient of increasing glycosylation from the stigmatic end to the ovarian end of the style, coincident with the direction of pollen tube growth. These results together suggest that the TTS protein-bound sugar gradient may contribute to guiding pollen tubes from the stigma to the ovary.

Cell Division

A tobacco gene family for flower cell wall proteins with a proline-rich domain and a cysteine-rich domain.

Flowering is known to be associated with the induction of many cell wall proteins. We report here five members of a tobacco gene family (CELP, Cys-rich extensin-like protein) whose mRNAs are found predominantly in flowers and encode extensin-like Pro-rich proteins. CELP mRNAs accumulate most abundantly in vascular and epidermal tissues of floral organs. In the pistil, CELP mRNAs also accumulate in a thin layer of cells between the transmitting tissue and the cortex of the style and in a surface layer of cells of the placenta in the ovary. This unique accumulation pattern of CELP mRNAs in the pistil suggests a possible role in pollination and fertilization processes. CELP genes encode a class of plant extracellular matrix proteins that have several distinct structural features: a Pro-rich extensin-like domain with Xaa-Pro3-7 motifs and Xaa-Pro doublets, a Cys-rich region, and a highly charged C terminus. The extensin-like domains in these proteins differ significantly in their length and these differences appear to be results of both long and short deletions within the coding regions of their genes. Furthermore, the number of charged amino acid residues in the C-terminal region varies among the CELPs. These structural differences may contribute to functional versatility in the CELPs. On the other hand, the Cys-rich domain is highly conserved among CELPs and the positions of the Cys residues are conserved, suggesting that this region may have a common functional role. The presence of a Pro-rich domain and a Cys-rich domain in these CELPs is reminiscent of a class of hydroxyproline-rich glycoproteins, solanaceous lectins, that are believed to be important in cell-cell recognition. The structure of these CELPs indicates that they may be multifunctional and that their genes may have arisen from recombinational events.

Amino Acid Sequence

Promiscuous germination and growth of wildtype pollen from Arabidopsis and related species on the shoot of the Arabidopsis mutant, fiddlehead.

When pollen lands upon the stigmatic surface of a receptive flower, recognition events take place that permit germination, pollen tube growth, and tube penetration into the cell walls of the stigmatic papillae. Previously, we have described a mutant of Arabidopsis thaliana, named fiddlehead (fdh), where noncarpel organs of the shoot fuse late in ontogeny (Lolle et al., 1992). Here we demonstrate that wildtype Arabidopsis pollen grows on noncarpel organs of the fdh mutant. Pollen grains adhere, germinate, and emit pollen tubes when applied to vegetative and nonreproductive floral organs. Some of the emergent pollen tubes penetrate into the cell wall. Although pollen from a number of closely related species responds, tomato, tobacco, and snapdragon pollen does not. In addition, we show that organ fusion is not a prerequisite for pollen growth and that root epidermis does not express this activity. Based on these findings we propose that the fdh mutation identifies an important regulatory gene that controls the expression of an epidermis-specific developmental program normally expressed only during gynoecial ontogeny.

Arabidopsis

Characterization of cDNAs for stylar transmitting tissue-specific proline-rich proteins in tobacco.

The pistil of flowers is a specialized organ which contains the female gametophytes and provides the structures necessary for pollination and fertilization. Pollen deposited on the stigmatic surface of a compatible plant germinates a pollen tube which penetrates the stigmatic papillae and grows intercellularly through the style towards the ovules in the ovary. Pollen tube growth is largely restricted to the transmitting tissue in the style. Therefore the stylar transmitting tissue is extremely important for the migration of the pollen cell towards the ovary. We have isolated two related cDNAs, transmitting tissue-specific (TTS)-1 and TTS-2, derived from two proline-rich protein (PRP)-encoding mRNAs that accumulate specifically in the transmitting tissue of tobacco. The deduced PRP sequences share similarities with proline-rich cell wall glycoproteins found in a variety of plants. TTS-1 and TTS-2 mRNAs are induced in very young floral buds, accumulate most abundantly during the later stages of flower development when style elongation is the most rapid, and remain at relatively high levels at anthesis. These mRNAs become undetectable in maturing green fruits. In situ hybridization shows that TTS-1 and TTS-2 mRNA accumulation is restricted to the transmitting tissue of the style. The possible roles that these transmitting tissue-specific PRPs may play in maintaining the structural integrity of the style or in the function of this organ is discussed.

Amino Acid Sequence

A flower-specific cDNA encoding a novel thionin in tobacco.

We isolated a flower-specific cDNA, FST (flower-specific thionin), which encodes a novel thionin from tobacco. Thionins are basic and cysteine (Cys)-rich, low molecular weight proteins found in many plants. They are believed to play a role in plant defense against pathogens. The central domain of the FST protein shares homology with three gamma-thionins. Like other thionin precursors, the FST protein has an N-terminal domain characteristic of a signal peptide and an acidic C-terminal domain. FST mRNA accumulates specifically in developing flowers and its level drops as flowers mature. Transcripts are present in petals, stamens and pistil but are not detectable in sepals. In situ hybridization revealed that FST mRNA is most abundant in the epidermal cells along the adaxial surface of petals, and in the surface cell layers of the carpel and anther walls. If the FST protein indeed has a protective role in flowers, this pattern of spatial distribution of FST mRNA would appear to maximize this effect on the two internal reproductive whorls. A possible biological role for FST is discussed.

Amino Acid Sequence

Fiddlehead: an Arabidopsis mutant constitutively expressing an organ fusion program that involves interactions between epidermal cells.

In most circumstances plant epidermal cells do not respond to surface contact with adjacent plant parts. We have identified and characterized a mutant of Arabidopsis thaliana, designated fiddlehead, where lateral appendages of the shoot fuse with one another. While fusion between floral organs is most frequent, leaf fusions also occur. Using scanning and transmission electron microscopy, we show that adhesion takes place between epidermal cells and does not involve cytoplasmic union. We also show that the frequency of organ fusion is dictated by organ proximity. In wildtype Arabidopsis, postgenital fusion takes place exclusively in the gynoecium, whereas in the fiddlehead mutant, this program becomes expressed constitutively. The existence of such a mutant demonstrates that postgenital fusion is a genetically distinct program superimposed upon other aspects of gynoecial development in Arabidopsis.

Cell Adhesion

Molecular analysis of an aurea photosynthetic mutant (Su/Su) in tobacco: LHCP depletion leads to pleiotropic mutant phenotypes.

Su is a nuclear encoded, semi-dominant aurea mutation in Nicotiana tabacum L. The homozygous plants (Su/Su) are pale yellow and non-photosynthetic while the heterozygous (Su/+) are photosynthetically competent and have a yellow-green phenotype which is distinct from that of green wild-type plants (+/+). We have examined the RNA and protein levels for a number of nuclear and plastid encoded chloroplast proteins under high and low light plant growth conditions. Under high light conditions, the light-harvesting chlorophyll a/b binding proteins (LHCP) were undetectable in the homozygous Su/Su plants, and the large subunit (LSu) and the small subunit (SSu) of ribulose bisphosphate carboxylase (Rubisco) and cytochrome b559 were severely deficient. However, only the nuclear encoded cab and plastid encoded psbE mRNA (encoding LHCP and cytochrome b559 respectively) were reduced significantly. In heterozygous Su/+ plants, the level of LHCP was reduced to 25% of that in wild-type plants while cab and psbE mRNA, LSu, SSu and cytochrome b559 remained at normal levels, suggesting that LCHP is more immediately affected by the Su mutant gene product than the rest of the photosynthetic proteins and mRNA examined. Under low light conditions, the levels of cab and psbE mRNA, LSu, SSu and cytochrome b559 in homozygous Su/Su plants were equivalent to those in wild-type plants except LHCP which remained undetectable. Similarly, the LHCP level in low light grown Su/+ plants still remained at 25% of wild-type level. These results indicate that the decrease in LHCP is independent of light conditions and has not resulted from photooxidation, whereas the depletion of other proteins and mRNA examined under high light growth conditions is a consequence of photooxidative damage to Su/Su plastids. Furthermore, transgenic Su/Su and Su/+ plants with a cauliflower mosaic virus 35S (CaMV 35S)-cab construct constitutively maintained high levels of cab mRNA but displayed the same pattern of diminished LHCP accumulation as their non-transformed counterparts when grown under both high and low light conditions. These results indicate that the Su mutation primarily causes depletion of LHCP. The depletion of LHCP leads to photooxidative damage which results in decreased cab mRNA levels and other pleiotropic lesions in Su/Su plants.

Genes, Plant

Vitamin K-dependent carboxylase: partial purification of the enzyme by antibody affinity techniques.

The vitamin K-dependent carboxylase activity of bovine liver microsomes has been purified 500-fold by adsorption to an antiprothrombin column and elution with a dodeca peptide which competes with a prothrombin precursor enzyme recognition site. The purified enzyme is devoid of bound precursors, and has the same ratio of vitamin K epoxidase activity to carboxylase activity as the crude microsomal preparation.

Animals

Radiotherapy for primary carcinoma of the trachea.

Between 1940 and 1985, 24 cases of primary carcinoma of the trachea were registered at the London Regional Cancer Centre. The most common presenting symptoms were hoarseness, haemoptysis and cough. Twenty patients had epidermoid carcinoma and four had adenoid cystic carcinoma. Because of different clinical behaviours, the two histologies were separately analyzed. Of the 20 patients with epidermoid carcinoma, 19 received radiotherapy as primary treatment and one patient did not receive radiotherapy because of advanced disease. Radiation doses ranged from 4000 to 6000 cGy and most patients had megavoltage irradiation. Treatment result was disappointing. Only one patient remained disease-free at 15-month follow-up and all other patients had persistent or recurrent tracheal tumour. Median survival for all 20 patients was 5 months (range 1 to 19 months). Of the four patients with adenoid cystic carcinoma, two had primary surgery and postoperative radiotherapy and two had primary radiotherapy. Two patients died of disease, at 5 months and 8 years from diagnosis. Two surviving patients had 15-month follow-up: one had persistent disease and the other was free from recurrence. In this study, radiotherapy within the range of doses given was found to be an ineffective primary treatment for tracheal carcinoma.

Adult

Cervical carcinoma: treatment results and complications of extended-field irradiation.

The authors studied treatment complications, recurrence patterns, and survival in 18 patients with histologically proved metastases to the paraaortic lymph nodes from invasive cervical carcinoma treated with extended-field irradiation. Complications following treatment developed in five of 10 patients who underwent transperitoneal nodal biopsy or dissection and in two of eight patients in whom an extraperitoneal approach was used (overall complication rate of 39%); however, only one had a gastrointestinal complication (small bowel obstruction after transperitoneal nodal biopsy and irradiation). Fourteen patients had persistent or recurrent disease within the abdominal or pelvic cavity; only one had distant metastases without recurrence in the abdomen or pelvis. Two of the 14 patients had a recurrence in the surgical scar following extraperitoneal nodal biopsy, possibly due to placement of the scar outside the radiation field. After a minimum follow-up of 48 months, only three of 18 patients (17%) were alive and well.

Combined Modality Therapy

Salvage radiotherapy for carcinoma of the ovary following chemotherapy.

Following single-agent or combination chemotherapy, 9 patients with epithelial carcinoma of the ovary had elective second-look laparotomy. Macroscopic intraperitoneal disease was resected in 4 patients. Therefore, after the laparotomy, all 9 patients had only biopsy-proven, microscopic residual disease, and they received whole abdominopelvic irradiation. Hematological tolerance was satisfactory, with only 2 patients developing asymptomatic thrombocytopenia. Mild gastrointestinal reactions, while frequent during radiotherapy, did not interrupt treatment in any patient. After follow-up from 12 to 34 months (median 16 months) [corrected], 2 patients died of cancer, 2 were alive with cancer, 3 were alive without clinical recurrence, and 2 were alive without biopsy-proven recurrence. Bowel complication occurred in 4 patients: 2 developed intestinal obstruction due to recurrent tumor, 1 developed subacute bowel obstruction which spontaneously resolved, and 1 patient required bowel resection because of a radiation complication. This study indicated that after single- or multiple-drug chemotherapy, most patients could complete the course of whole abdominopelvic irradiation. Gastrointestinal complications could be secondary to radiation damage or to recurrent tumor. While whole abdominopelvic irradiation was not an effective second-line treatment, some long-term survivors could still be expected.

Carcinoma

Effects of a sonographic technique for determining chest wall thickness in treatment planning for breast carcinoma.

This study investigated the use of a sonographic technique of determining chest wall thickness and the impact of dosimetric correction for lung inhomogeneity on treatment planning for breast irradiation after lumpectomy or partial mastectomy. The thickness of the chest wall in three planes of the radiation field was obtained using a B-mode ultrasound scanner and the location of the pleura-lung interface was marked on the contour of the chest wall in each plane. Treatment plans for 88 patients were developed with and without correction for the lung tissue included in the radiation volume. All patients were irradiated with an opposing pair of tangential fields to the breast with a 6 MV X ray beam using an isocentric set-up. Within the treatment volume, dose variation of +/- 5% of the prescribed tumor dose was aimed for in the treatment planning. With correction for lung tissue, the proportion of treatments given with a wedge filter was found to be on the average 20% less than it would be without lung correction. The described sonographic technique is simple to perform and reproducible. It improves the accuracy of dosimetry in treatment planning for breast carcinoma.

Breast Neoplasms