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Biomedical subjects

M C Liu

Publications and source records attributed to M C Liu.

At least 91 records · Page 5Linked to original sources
PubMed1998

Preoperative concurrent chemotherapy and radiotherapy in rectal cancer patients.

The management of rectal cancer has changed significantly in recent years. The key end-point is no longer survival but rather preservation of sphincter function with improved quality of life. Preoperative radiation can not only render a low-lying rectal tumor amenable to sphincter-preserving surgery but has also been reported to give better local control and lower toxicity than postoperative radiotherapy. From October 1991 through July 1996, 46 patients with local advanced or low-lying rectal cancer were treated with preoperative high-dose radiotherapy and concurrent chemotherapy. All patients underwent pelvic radiotherapy with 5,000 to 5,400 cGy in 25 to 27 fractions. Chemotherapy was given concomitantly and consisted of two courses of 5-fluorouracil (5-FU) at 1,000 mg/m2 for 4 days in week 1 and week 5 plus mitomycin C 10 mg/m2 single bolus on day 1 of week 1. In 30 patients, postoperative adjuvant chemotherapy with 5-FU and levamisole weekly was also given, for a total of 12 months. The most common acute toxicity was grade 1 to 2 diarrhea and tenesmus during radiation or soon afterward. Only five of the 46 patients experienced symptomatic grade 3 acute toxicity. Forty-two patients underwent subsequent surgery 6 to 8 weeks after concurrent chemoradiotherapy. Pathologic examination disclosed complete tumor regression in eight patients and microscopic residual disease in 13 patients after preoperative chemoradiation. Of the 42 patients who completed the intended treatments, only one had local recurrence. The sphincter was preserved in 21 of the 26 patients in whom the tumor was located within 5 cm above the anal verge. Twelve of the 16 evaluable patients had good to excellent sphincter function. The 2-year overall survival rate was 93% and the disease-free survival was 81%. Our findings indicate that preoperative concurrent chemoradiotherapy not only allows low-lying rectal tumors to be resected while preserving sphincter function but also results in good local control and acceptable toxicity.

Adenocarcinoma↗
PubMed1997

Overexpression of the multidrug resistance genes mdr1, mdr3, and mrp in L1210 leukemia cells resistant to inhibitors of ribonucleotide reductase.

L1210 MQ-580 is a murine leukemia cell line resistant to the cytotoxic activity of the alpha-(N)-heterocyclic carboxaldehyde thiosemicarbazone class of inhibitors of ribonucleotide reductase. The line is cross-resistant to etoposide, daunomycin, and vinblastine. L1210 MQ-580 cells expressed 8-fold resistance to 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), a relatively newly developed inhibitor of ribonucleotide reductase. The accumulation of [14C]3-AP by L1210 MQ-580 cells was 5- to 6-fold less than by parental L1210 cells. An increased rate of efflux of 3-AP was responsible for the lower steady-state concentration of 3-AP in resistant cells. In reverse transcription-polymerase chain reaction assays, L1210 MQ-580 cells were found to overexpress the multidrug resistance genes mdr1, mdr3, and mrp, but not the mdr2 gene, compared with parental L1210 cells. Measurement of the steady-state concentration of doxorubicin, a potential substrate for both the mdr and mrp gene products, demonstrated that L1210 MQ-580 cells accumulated 4-fold less anthracycline than parental cells. These findings indicate that drug efflux is a major determinant of the pattern of cross-resistance of L1210 MQ-580 cells. To extrapolate these observations to the human homologues of the mdr1, mdr3, and mrp murine genes, the effects of 3-AP were measured in L1210/VMDRC0.06 and NIH3T3 36-8-32 cells transfected with human MDR1 and MRP cDNAs, respectively. The transfectants were 2- to 3-fold resistant to the cytotoxic effects of 3-AP and accumulated less [14C]3-AP than their parental mock-transfected counterparts. Moreover, the cytotoxic activity of 3-AP was significantly greater in two double mrp gene knockout cell lines than in parental W 9.5 embryonic stem cells. Thus, the results suggest that 3-AP is a substrate for both the P-glycoprotein and MRP and that baseline MRP expression has the capacity to exert a protective role against the toxicity of this agent.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1997

Manganese-dependent Dopa/tyrosine sulfation in HepG2 human hepatoma cells: novel Dopa/tyrosine sulfotransferase activities associated with the human monoamine-form phenol sulfotransferase.

Human monoamine (M)-form phenol sulfotransferase (PST) was PCR-cloned and transiently expressed in COS-7 cells. The recombinant enzyme was demonstrated to display not only the previously reported sulfotransferase activity toward dopamine, but also novel manganese-dependent Dopa/tyrosine sulfotransferase activities. These results imply a new functional role of the human M-form PST in the homeostatic regulation of Dopa and tyrosine.

Animals↗
PubMed1997

Tissue-specific and developmental stage-dependent expression of a novel rat Dopa/tyrosine sulfotransferase.

Tissue-specific and developmental stage-dependent expression of a novel Dopa/tyrosine sulfotransferase in Sprague-Dawley rats was examined. Both immunoblot and Northern blot analyses showed that the enzyme was expressed predominantly in liver and to a lesser extent in kidney. Its expression could not be detected in nine other organs tested. Livers from different age groups of male or female rats were examined for the developmental regulation of the expression of the Dopa/tyrosine sulfotransferase. Results from immunoblot and Northern blot analyses revealed that the enzyme was present at a very low level in livers of 1-day-old to 2-week-old rats, and gradually increased to a maximum level in rats older than 2 months. Data from the enzymatic assays also showed a similar trend of expression in both male and female rats. The Dopa/tyrosine sulfotransferase activities detected in liver samples of the 8-week-old male and female rats were, respectively, 8.6 and 6.6 times that of the activities detected in liver samples of the 1-day-old male and female rats. These data provide a foundation for the future investigation of the cis- and trans-acting factors involved in the regulation of the tissue-specific and developmental stage-dependent expression of this enzyme.

Aging↗
PubMed1997

Clonal chromosomal abnormalities as direct evidence for clonality in nasal T/natural killer cell lymphomas.

Nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity which is more prevalent in Asia than in America and Europe. The clonal nature of the infiltrating lymphoid cells is difficult to demonstrate because of the lack of immunologic markers for clonality and the absence of clonal T-cell receptor gene rearrangement in most cases. In this study, clonal chromosomal abnormalities were detected in the tumour cells from four patients with nasal T/NK cell lymphoma. This finding provided direct evidence for clonality of the disease. Moreover, nonrandom cytogenetic abnormalities, including isochromosome for the short arm (p) of chromosome 6, isochromosome for the long arm (q) of chromosome 1, partial deletion of 6q, and aberrations at 11q, were disclosed. Isochromosome 6p was the sole structural abnormality in one patient, which may be a pathognomonic change in nasal lymphoma.

Adult↗
PubMed1997

Phenotypic analysis of alveolar macrophages and monocytes in allergic airway inflammation. I. Evidence for activation of alveolar macrophages, but not peripheral blood monocytes, in subjects with allergic rhinitis and asthma.

Macrophages and monocytes play important proinflammatory roles in allergic inflammation. We hypothesized that these cells would express an activated phenotype in allergic disease of the airways. We therefore compared the expression of 17 activation markers on the surface of alveolar macrophages (AM) and peripheral blood monocytes (PBM) in 13 subjects with asymptomatic allergic asthma (AA), nine subjects with asymptomatic allergic rhinitis (AR), and 11 nonallergic (N). AM were obtained by BAL, and PBM were simultaneously obtained by phlebotomy; both were analyzed for expression of surface markers using a new two-color flow cytometry method that essentially eliminates background autofluorescence. The proportions of AM in BAL fluid from AA, AR, and N subjects were 84 +/- 2, 85 +/- 4, and 91 +/- 1%, respectively; viability always exceeded 92%. Expression of eight markers (CD16, CD18, CD32, CD44, CD71, HLA Class I, HLA DR, and HLA DQ) was significantly (p < 0.05) higher on AM of AA than on N; expression of six markers (CD11a, CD16, CD18, CD71, HLA Class I, and HLA DR) was higher on AM of AR than on N, with differences in CD44 levels approaching statistical significance (p = 0.07). Expression of one marker, CD44, was significantly higher on AM of AA than on those of AR, with differences in HLA Class I levels approaching statistical significance (p = 0.07). In contrast, no significant differences were found among the three groups in the expression in eight other markers (CD11b, CD14, CD23, CD29, CD33, CD35, CD63, and CD64). Finally, similar analysis of PBM from these same subjects failed to find any difference between the three groups in any of the 17 activation markers studied. These data suggest that AM are activated in allergic respiratory diseases, and that levels of HLA Class I and CD44 on AM are altered during allergic inflammation in the upper and lower airways.

Adult↗
PubMed1997

Characterization of bovine heart sulfotransferase catalyzing the sulfation of tyrosine-containing peptides.

Using [35S]PAPS as the sulfate donor, we have detected a sulfotransferase from bovine heart which catalyzes the sulfation of tyrosine-containing peptides. The enzyme displayed optimal activity at pH 5.75 and 35 degrees C in a one-hour reaction. The addition of 10 mM Mn2+ or Co2+ to the reaction mixture increased the sulfotransferase activity by 3.4- and 3.5-fold, respectively. In contrast, the maximum increment stimulated by Mg2+ was only 1.75-fold at 15 mM concentration, and instead of exerting an enhancement effect, Ca2+ was found to be a potent inhibitor. The addition of 50 mM NaF to the reaction mixture resulted in an increase in sulfotransferase activity of 3.3-fold. The K(m) for 3'-phosphoadenosine 5'-phosphosulfate (PAPS) was determined to be 2 microM at a constant 0.5 mM Boc-Glu-Asp-Tyr-Val. Among the 10 peptides tested as substrates, Boc-Glu-Asp-Tyr-Val and Boc-Asp-Asp-Tyr-Val provided the highest activities.

Amino Acid Sequence↗
PubMed1996

Synthesis and biological activity of 3- and 5-amino derivatives of pyridine-2-carboxaldehyde thiosemicarbazone.

A series of 3- and 5-alkylamino derivatives, as well as other structurally modified analogues of pyridine-2-carboxaldehyde thiosemicarbazone, have been synthesized and evaluated as inhibitors of CDP reductase activity and for their cytotoxicity in vitro and antineoplastic activity in vivo against the L1210 leukemia. Alkylation of 3- and 5-amino-2-(1,3-dioxolan-2-yl)pyridines (1, 2) resulted in corresponding 3-methylamino, 5-methylamino, 3-allylamino, 5-ethylamino, 5-allylamino, 5-propylamino, and 5-butylamino derivatives (5, 6, and 11-15), which were then condensed with thiosemicarbazide to yield the respective thiosemicarbazones (7, 8, and 16-20). Oxidation of 3,5-dinitro-2-methylpyridine (21) with selenium dioxide, followed by treatment with ethylene glycol and p-toluenesulfonic acid, produced the cyclic ethylene acetal, 23. Oxidation of 2-(1,3-dioxolan-2-yl)-4-methyl-5-nitropyridine (26) with selenium dioxide, followed by sequential treatment with sodium borohydride, methanesulfonyl chloride, and morpholine afforded the morpholinomethyl derivative 30. Catalytic hydrogenation of 23 and 30 with Pd/C yielded the corresponding amino derivatives 24 and 31. Catalytic hydrogenation of 5-cyano-2-methylpyridine (33) with Raney nickel, followed by treatment with acetic anhydride, gave the amide derivative 35. N-Oxidation of 35, followed by rearrangement with acetic anhydride, produced the acetate derivative, 5-[(acetylamino)methyl]-2-(acetoxymethyl)pyridine (37). Repetition of the N-oxidation and rearrangement procedures with compound 37 yielded the diacetate derivative 39. Condensation of compounds 24, 31, and 39 with thiosemicarbazide afforded the respective 3,5-diaminopyridine-, 4-(4-morpholinylmethyl)-5-aminopyridine-, and 5-(aminomethyl)pyridine-2-carboxaldehyde thiosemicarbazones (25, 32, and 40). The most biologically active compounds synthesized were the 5-(methylamino)-, 5-(ethylamino)-, and 5-(allylamino)pyridine-2-carboxaldehyde thiosemicarbazones (8, 17, and 18), which were potent inhibitors of ribonucleotide reductase activity with corresponding IC50 values of 1.3, 1.0, and 1.4 microM and which produced significant prolongation of the survival time of L1210 leukemia-bearing mice, with corresponding optimum % T/C values of 223, 204, and 215 being obtained when administered twice daily for six consecutive days at dosages of 60, 80, and 80 mg/kg, respectively.

Animals↗
PubMed1996

Enhanced expression of IL-12 associated with Th1 cytokine profiles in active pulmonary sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by the expansion of activated oligoclonal CD4+ T cells and macrophages at sites of disease. To investigate the immunopathogenesis of sarcoidosis, we analyzed patterns of cytokine expression in bronchoalveolar lavage cells and fluid from patients with pulmonary sarcoidosis and idiopathic pulmonary fibrosis and from normal volunteers. We found dominant type 1 cytokine expression, with elevated mRNA and protein levels of IFN-gamma, but not IL-4, in sarcoid lung cells and fluid compared with those in normal samples. To define immunoregulatory mechanisms important to this type 1 response, we analyzed the expression of IL-12 and IL-10 in lung cells and fluid. Using semiquantitative PCR, we found significantly higher mRNA expression of the regulated IL-12 p40 subunit, but not IL-10, in sarcoid compared with normal lung cells. Consistent with these observations, strikingly elevated levels of p40 protein were found in sarcoid compared with normal bronchoalveolar lavage fluid. Unstimulated and Staphylococcus aureus-stimulated sarcoid alveolar macrophages produced greater amounts of IL-12 than normal alveolar macrophages when cultured in vitro. We hypothesize that sarcoidosis is a Th1-mediated disease driven by chronic, dysregulated production of IL-12 at sites of disease.

Adult↗
PubMed1996

Antigen-induced generation of lyso-phospholipids in human airways.

The goal of the current study was to examine the formation of phospholipids, 1-radyl-2-lysosn-glycero-phospholipids (lyso-PL) and 2-acetylated phospholipids (such as PAF) as well as mechanisms responsible for generating these phospholipids in bronchoalveolar lavage fluid (BAI.F) from allergic subjects challenged with antigen. Bronchoalveolar lavage was performed in normal and allergic subjects before, 5-30 min, 6 h, and 20 h after segmental antigen challenge via a wedged bronchoscope. Levels of 1-hexadecyl-2-lyso-phospholipids and 1-hexadecyl-2-acetyl-phospholipids were initially determined by negative ion chemical ionization gas chromatography/mass spectrometry (NICI-GC/MS). Antigen dramatically elevated quantities of 1-hexadecyl-2-lyso-phospholipids in allergic subjects 20 h after challenge when compared to non-allergic controls. In contrast, there was not a significant increase in levels of 1-hexadecyl-2-acetyl-phospholipids after antigen challenge. Closer examination of 1-radyl-2-lyso-sn-glycero-3-phosphocholine (GPC) revealed that 1-palmitoyl-2-lyso-GPC, 1-myristoyl-2-lyso-GPC and 1-hexadecyl-2-lyso-GPC were three major molecular species produced after antigen challenge. 1-palmitoyl-2-lyso-GPC increased sevenfold to levels of 222 +/- 75 ng/ml of BALF 20 h after antigen challenge. The elevated levels of lyso-PL correlated with levels of albumin used to assess plasma exudation induced by allergen challenge. In contrast, the time course of prostaglandin D2 (PGD2) or 9 alpha, 11 beta PGF2 (11 beta PGF2) formation did not correlate with lyso-PL generation. To examine the mechanism leading to lyso-phospholipid formation in antigen-challenged allergic subjects, secretory phospholipase A2 (PI.A2) and acetyl hydrolase activities were measured. There was a significant increase in PLA2 activity found in BALF of allergic subjects challenged with antigen when compared to saline controls. This activity was neutralized by an antibody directed against low molecular mass, (14 kD) human synovial PLA2 and dithiothreitol. Acetyl hydrolase activity also markedly increased in BALF obtained after antigen challenge. This study indicates that high levels of lyso-PLs are present in airways of allergic subjects challenged with antigen and provides evidence for two distinct mechanisms that could induce lyso-PL formation. Future studies will be necessary to determine the ramifications of these high levels of lyso-phospholipids on airway function.

Adult↗
PubMed1996

Enzymic sulphation of dopa and tyrosine isomers by HepG2 human hepatoma cells: stereoselectivity and stimulation by Mn2+.

HepG2 human hepatoma cells, labelled with [35S]sulphate in media containing L-3,4-dihydroxyphenylalanine (L-dopa), (D-dopa), DL-m-tyrosine or D-p-tyrosine, were found to produce the [35S]sulphated forms of these compounds. Addition to the labelling media of m-hydroxybenzylhydrazine, an aromatic amino acid decarboxylase inhibitor, greatly enhanced the production of L-dopa O-[35S]sulphate and DL-m-tyrosine O-[35S]sulphate, with a concomitant decrease in the formation of dopamine O-[35S]sulphate and m-tyramine O-[35S]sulphate. With 3'-phosphoadenosine 5'-phospho[35S]sulphate as the sulphate donor., HepG2-cell cytosol was shown to contain enzymic activity catalysing the sulphation of L-dopa, D-dopa, L-m-tyrosine, D-m-tyrosine, L-p-tyrosine and D-p-tyrosine. The pH optimum of the enzyme, designated dopa/tyrosine sulphotransferase, was determined to be 8.75 with D-m-tyrosine as the substrate. The enzyme exhibited stereoselectivity for the D-form of dopa or tyrosine isomers. Addition of 10mM MnCl2 to the reaction mixture resulted in a remarkable stimulation of dopa/tyrosine sulphotransferase activity, being as high as 267.8 times with D-p-tyrosine as the substrate. Quantitative assays revealed L-dopa, D-dopa and D-m-tyrosine to be better substrates than L-p-tyrosine. When the HepG2-cell cytosol was subjected to DEAE Bio-Gel and hydroxyapatite column chromatography, dopa/tyrosine sulphotransferase was co-eluted with the thermolabile 'M-form' phenol sulphotransferase. Furthermore dopa/tyrosine sulphotransferase displayed properties similar to that of the M-form phenol sulphotransferase with respect to thermostability and sensitivity to 2,6-dichloro-4-nitrophenol. Whether the M-form phenol sulphotransferase is truly (solely) responsible for the dopa/tyrosine sulphotransferase activity present in HepG2 cells remains to be clarified.

Blood Platelets↗
PubMed1996

Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group.

BACKGROUND: Leukotrienes produced by the 5-lipoxygenase pathway of arachidonic acid metabolism may mediate bronchoconstriction and inflammatory changes important in the pathophysiology of asthma. Leukotriene inhibition may be effective in asthma management. OBJECTIVE: This clinical trial was performed to assess the long-term efficacy and safety of zileuton, an inhibitor of 5-lipoxygenase. METHODS: In this multicenter, double-blind, parallel-group, placebo-controlled trial, 600 mg of zileuton, 400 mg of zileuton, or placebo was given orally, each four times daily for 6 months. Patients with mild to moderate asthma (n = 373), 18 to 62 years of age, being managed with regularly inhaled beta-agonist alone, were randomized to the zileuton or placebo groups (n = 122 to 126). Outcome measures included serial spirometry, daily peak expiratory flow rates, daytime and nocturnal symptoms, frequency of beta-agonist use, and number of asthma exacerbations treated with systemic corticosteroids. RESULTS: An acute bronchodilatory effect was observed 2 to 5 hours after the initial dose of medication in both 400 mg zileuton and 600 mg zileuton groups compared to the placebo group. Both zileuton groups had significantly greater improvements in FEV1 than did the placebo group by day 8. On day 36, FEV1 improved 16% and 12% from baseline for patients treated with 600 mg zileuton and 400 mg zileuton, respectively, compared with an improvement of 6% for the placebo-treated group (p < 0.01, zileuton 600 mg vs placebo). Blood eosinophil levels were significantly reduced in both zileuton-treated groups compared with the placebo group. In the group receiving 600 mg zileuton, morning peak expiratory flow rate improved by 7% to 10%; daytime and nocturnal symptoms decreased by 37% and 31%, respectively; beta-agonist use decreased by 31%; and the proportion of patients requiring steroid rescue medication during the study was reduced by 62% (p < 0.05 for all comparisons of zileuton, 600 mg, vs placebo). Improvements were sustained over 6 months. Adverse events were similar in the three groups with no apparent, dose-related side effects. CONCLUSION: Zileuton produces objective and subjective improvements in patients with mild to moderate asthma and is well tolerated.

Adolescent↗
PubMed1996

Dissociation of bradykinin-induced plasma exudation and reactivity in the peripheral airways.

To determine if bradykinin, a potential mediator of asthma, acts, at least in part, at the level of the peripheral airways, we used a wedged bronchoscope technique to study asthmatic and normal subjects. Baseline peripheral airways resistance (Rp) was measured in the right upper lobe. Subjects then received saline, followed by increasing doses of bradykinin, aerosolized through the bronchoscope. Rp was measured after each challenge. At the end of the procedure, bronchoalveolar lavage was performed in both the challenged and a control segment. Fibrinogen content of recovered lavage fluids was measured as an index of plasma exudation. Bradykinin induced a dose-dependent increase in Rp in the asthmatics, but did not effect Rp in normal subjects. In asthmatics, there was no significant correlation between peripheral airways reactivity and whole lung reactivity to bradykinin. Fibronogen increased significantly in both groups after bradykinin challenge, and there was no significant difference between postchallenge levels for the two groups. Thus, hyperreactivity of the peripheral airways in asthmatics is not directly due to plasma exudation. The ability of bradykinin to increase peripheral airways resistance in asthmatic, but not in normal, subjects is consistent with a role of this peptide as a mediator of asthma.

Adult↗
PubMed1996

Desulfation of tyrosine-O-sulfated peptides by some eukaryotic sulfatases.

Three mammalian and eight non-mammalian arylsulfatases were investigated for their activities toward tyrosine-O-sulfate (TyrS) in peptides. None of the mammalian arylsulfatases exhibited detectable activities toward TyrS-containing peptides. Of the non-mammalian arylsulfatases tested, Types VII, VIII, and H-1, 2, and 5 displayed strong activity on endo-TyrS residues. The prokaryotic sulfatase, Type VI, was active only on free TyrS and N-terminal TyrS of Leu-enkephalin. All the sulfatases were active on p-nitrophenyl sulfate and p-nitrocatechol sulfate.

Peptides↗
PubMed1996

Breast-conserving surgery and radiotherapy for early breast cancer.

Breast conservation is not a commonly prescribed treatment option for breast cancer in Taiwan. We report 42 patients with 43 early-stage breast cancers who were treated with breast-conserving surgery and radiotherapy at the Koo Foundation Sun Yat-Sen Cancer Center from April 1990 to December 1994. Included in this study were 33 patients with stage I cancers and 10 with stage II. Breast-conserving surgery consisted of wide local excision and ipsilateral axillary lymph node dissection. Radiotherapy was given 2 to 6 weeks after surgery, with a dose of 46 to 50 Gy, 2 Gy per fraction per day, to the whole breast, and an additional 14 to 18 Gy to the original tumor site. Irradiation to the regional lymph nodes was not performed in patients with negative axillary lymph nodes. Sixteen out of 43 (37%) patients were treated with adjuvant chemotherapy. The local control rate 3 years after treatment was 97% and relapse-free survival was 91%. The cosmetic outcome in 41 treated breasts that were rendered relapse-free by conserving treatment were evaluated and graded by the physicians as excellent, good, fair or poor using a standardized scale. Forty breasts (98%) were scored as excellent or good for their cosmetic results. Breast-conserving surgery and radio-therapy offer Taiwanese women with early breast cancer excellent local control and a highly satisfactory cosmetic outcome.

Adult↗
PubMed1996

Organ preservation approaches with radiation therapy in muscle-invasive bladder carcinoma.

Combined modality treatments with organ preservation intent have become standard oncological treatment in many tumour sites. Although radical cystectomy had been considered to be the standard treatment, combined modality treatment has been used in muscle-invasive bladder carcinoma with excellent results, especially in patients with T2-3a disease without obstructed ureters. The components of the combined treatment are usually transurethral resection of bladder tumour (TURBT) followed by concurrent chemotherapy and radiation. Interim cystoscopic assessment after the initial portion of radiation is often utilised to identify patients at high risk of local failure, ie. those who do not achieve a complete response, and these patients are then recommended to undergo immediate salvage cystectomy. Delaying cystectomy does not appear to decrease the survival or increase the incidence of distant metastasis. The local control rates for TURBT alone, chemotherapy alone and radiation therapy alone are only 20%, 20% and 30% to 45% respectively. When the above three are combined together, a complete response rate of 75% can be achieved and 85% of these remain free from invasive recurrence. Combined modality treatment offers an overall survival rates which is comparable with modern radical cystectomy series: about 50% at 5 years, and in addition, it offers a 5-year survival rate with an intact bladder of 41% to 43%. With the close collaboration among urologists, medical oncologists and radiation oncologists, organ preservation approaches can achieve excellent results in muscle-invasive bladder carcinoma and this option should be presented to patients as an alternative to radical cystectomy.

Carcinoma↗