Review ArticleReviewsR

In Vitro and In Vivo Experimental Models as Tools to Investigate the Efficacy of Antineoplastic Drugs on Urinary Bladder Cancer

REGINA ARANTES-RODRIGUES, AURA COLAÇO, ROSÁRIO PINTO-LEITE and PAULA A. OLIVEIRA
Anticancer Research April 2013, 33 (4) 1273-1296;

Abstract

Several drugs have shown in vitro and in vivo pharmacological activity against urinary bladder cancer. This review aims at compiling the different drugs evaluated in in vitro and in vivo models of urinary bladder cancer and to review the advantages and limitations of both types of models, as well as the different methodologies applied for evaluating antineoplastic drug activity.

Cancer is one of the most important public health issues and the most feared human disease (1). It is the second leading cause of death after coronary heart diseases and one in three persons suffers from cancer throughout their lives and one in four will die from this disease (2). Urinary bladder cancer is a common disease that ranks ninth in worldwide cancer incidence. It is the fourth most common cancer in men and the ninth in women, with a probability of developing in men three-times higher than in women, and with a ratio of 2:1 for caucasians and negros, respectively (3). The risk for developing this disease increases with age, with a peak between 60 and 70 years (4). Remarkable differences can be found in its incidence, it being predominately higher in developed countries such as in North America, Western and Southern Europe (5). In less industrialized countries, such as in Asia, Africa and the Middle East, the incidence of urinary bladder cancer is lower except for regions where Schistosoma haematobium is endemic. In these cases, urinary bladder squamous cell carcinoma is common (6). Involving exogenous and endogenous factors, the aetiology of urinary bladder cancer is multifactorial (Figure 1) (7, 8). Cigarette smoking, and environmental and occupational exposure to chemical agents remain the two major risk factors (7).

Urinary bladder cancer is classified into three main types: transitional cell carcinoma, squamous cell carcinoma and adenocarcinoma. At minor percentages are the small-cell tumours (1%) and sarcomatoid tumours (fewer than 1%) (9). Accounting for more than 90% of all cases, transitional cell carcinoma is the most common form of urinary bladder cancer (10). At diagnosis, nearly 70% of patients with urinary bladder cancer present with non-muscle-invasive lesions. Several clinical factors, such as tumour multiplicity, diameter, concomitant carcinoma in situ (CIS) and gender, have been identified as having prognostic significance for recurrence (11). CIS represents a major concern in the treatment of non-muscle-invasive lesions. CIS is a high-grade lesion that is characterized by disorderly proliferation of cells with marked cytological abnormalities (12). Although the European Association of Urology recommends transurethral resection and intra-vesical Bacillus Calmette-Guerin (BCG) immunotherapy for patients with CIS lesions, which achieves a complete response rate, 20% of patients will ultimately die of metastatic disease (12-14). The remaining 30% of patients at diagnosis have muscle-invasive lesions and 10% of these cases has a tendency to metastasize, with a poor prognosis (15).

Urinary Bladder Cancer Treatment

Treatment of non-muscle-invasive lesions. Complete transurethral resection is the standard treatment for non-muscle-invasive lesions (16). Despite good prospects of survival (success rate of 80%), these tumours recur in approximately 70% of patients (10). One of the major challenges in treating non-muscle-invasive tumours is to reduce the high frequency of early recurrences, detected in more than 45% of the patients, three months following transurethral resection (17). In order to reduce the recurrence risk and to delay or prevent progression to a muscle-invasive lesion, after transurethral resection, adjuvant intra-vesical instillations of chemotherapy or immunotherapy are widely applied with mitomycin C (MMC) and BCG, respectively (16). Use of BCG not only reduces the recurrence rate, but also reduces the risk of a non-muscle-invasive lesion progressing to a muscle-invasive lesion, improving the overall survival (7). The role of BCG in urinary bladder cancer was clinically studied for the first time in 1976, by Morales and collaborators, which found a complete response in seven out of nine patients treated (18). Although treatment with BCG provides better results than transurethral resection without immunotherapy, side-effects arising from its administration are a concern. The development of sepsis, cystitis, dysuria and mild haematuria are frequently reported (19). However, with increased experience in using BCG, the side-effects now appear to be less prominent (20). Intravesical chemotherapy with MMC, epirubicin and doxorubicin have all shown comparable beneficial effects (21).

Figure 1.
Figure 1.

Risk factors that contribute to the development of urinary bladder cancer. GSTM1: Glutathione S-transferase Mu; NAT2: N-acetyltransferase-2 (arylamine N-acetyltransferase).

Treatment of muscle-invasive lesions. The treatment options that are currently available for the management of muscle-invasive urinary bladder cancer include radical cystectomy and chemotherapy-plus-radiation therapy, with the goal of bladder preservation. Combined chemotherapy based on methotrexate, vinblastine, adriamycin and cisplatin (MVAC) was initiated in the 1980s, leading to a disease-free survival rate of 3.7% at six years (22). However, this protocol was highly toxic, with severe side-effects, being associated with a mortality rate of about 4% (23). Thus, new approaches are being continuously investigated to provide superior efficacy with lower toxicity (24).

In Vitro and In Vivo Models for the Study of Urinary Bladder Cancer

Experimental models are used to better explain tumour behaviour, to evaluate the effect of chemopreventive agents, and to study the efficacy of antineoplastic drugs (25). Such experimental research can be achieved by means of in vitro and in vivo models.

In vitro models. To date, cultured urinary bladder cells represent the most frequently used in vitro bladder cell model. These models usually consist of isolated urinary bladder cancer cell lines and have been established as a valid in vitro model not only to study the mechanism involved in urinary bladder cancer development but also to evaluate anti-neoplastic drug efficacy (26). In 1970, Rigby and Franks established the first human urinary bladder cancer cell line, designated as RT4 (27). Since then, many other human urinary bladder cancer cell lines have been established and characterized according to their origin, grade and stage. A great proportion of these cell lines was established from invasive and metastic tumours, benefiting the investigation of late tumour progression and metastic lesions. On the other hand, few non-muscle-invasive human urinary bladder cancer cell lines are available, which is a disadvantage in the investigation of non-muscle-invasive urinary bladder cancer (26). Urinary bladder cancer cell lines may also be established from rodents exposed to urothelial chemical carcinogens. In 1971, Toyoshima and collaborators established the Nara urinary bladder cancer II (NBT-II) cell line, a rat cell line obtained from a urinary bladder tumour chemically induced by N-Butyl-N-(-4-hydroxybutyl) nitrosamine (BBN) (28). In the same year, three more urinary bladder cancer cell lines were established from tumours induced by the combined use of N-2-fluorenylacetamide and cyclophosphamide in Fischer 344 female rats, two of them epithelial (BC5 and BC6) and one fibroblastic (BC7) (29). Five years later, two mouse urinary bladder cancer cell lines were established using the carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and, more recently, seven chemically-induced mouse urinary bladder cancer cell lines (BC13, BC29, BC30, BC46, BC57, BC58 and BC59) were established from tumours developed in C57BL/6 mice exposed to BBN (30). Table I summarizes commercially available human and rodent urinary bladder cancer cell lines.

View this table:
Table I.

Established human and rodent urinary bladder cancer cell lines.

Under specific culture conditions, normal human urothelial cells may be also established from surgical specimens of urinary bladder (31). These normal cells can be used to evaluate mechanisms by which therapeutic agents interact with normal human urothelial cells and to verify if antineoplastic drugs can induce cell damage. Tumours are, however, three-dimensional complexes in which there is great interaction between tumourous and non-tumourous cells. Thus, cell culture represents an artificial system for investigating features such as vascularization and perfusion (32). Urothelium may be maintained in combination with stroma as a three-dimensional heterotypic or organotypic culture. Such organoids may either be established from intact tissues, or recombined from reconstructed urothelial and stromal compartments prior to culture and may be maintained up to 20 weeks in culture (33). Chang and collaborators were pioneers in using human urinary bladder tumour specimens in three-dimensional histoculture to assess the activity of a new platinum analog (34). The growth of tumour cells as three-dimensional multicellular spheroids in vitro has led to important insights in tumour biology, since properties of the in vivo tumour, such as proliferation, and nutrient gradients, can be studied under controlled conditions (35). Moreover, three-dimensional culture allows for an understanding of basic paracrine signalling mechanisms that regulate tissue homeostasis, development of new methods for urinary bladder reconstruction and tissue engineering, and generation of models of malignant and benign diseases (33). Furthermore, isolated organs allow an approach towards the assessment of organ physiology and morphology, providing with models that mimic conditions in humans more closely (26). Several years ago, Burgués and collaborators tested several drugs (epirubicin, thiotepa, adriamycin, MMC, verapamil and ciprofloxacin) on ex vivo spheroids of non-muscle-invasive urinary bladder cancer. Their study suggests that use of three-dimensional urinary bladder cultures could be a possible approach in clinical practice to select for the best antineoplastic drug for each patient and to investigate the effect of new antineoplastic drugs or drug combinations (36).

In vivo models. Prediction of drug activity in patients with cancer based only on in vitro studies is not reliable, and animal models are widely recognized as being essential to the study of antineoplastic drug efficacy (32). Animal models were defined by Wessler in 1976 as “living organisms with an inherited naturally-acquired or induced pathological process that closely resembles the same phenomenon in man”. Their application in biomedical research, and pathophysiological and toxicological studies, allows us to determine aetiological factors, study cancer development and progression, and to develop new medical devices or therapies (37).

For an appropriate and valid animal model for the study of urinary bladder carcinogenesis to exist, several requirements are necessary: the tumour should be of urothelial origin with different stages of disease progression, it should grow intravesically so as to be directly exposed to antineoplastic drugs, it should mimic the pathogenesis of human urinary bladder cancer, and it should present stable molecular and genetic alterations similar to those found in human urinary bladder cancer (38). Several animal species such as dogs, rabbits, guinea pigs, and hamsters may be used. However, rats and mice are the animals most employed, due to their small size, innumerable anatomical, physiological and biochemical similarities to humans, clear genetic background and high reproductive rate. Furthermore, the occurrence of spontaneous tumours in laboratory rodents is uncommon, which is one reason why they are considered as ideal models for the study of chemically-induced urinary bladder cancer (38).

Recently, a study conducted by Palmeira and collaborators described the similarities found between human urinary bladder carcinogenesis and rodent chemically-induced urinary bladder carcinogenesis in regards to the histopathological features and biological alteration profile, namely: DNA aneuploidy, p53 overexpression and high Ki-67 proliferative index. They reported that the spectrum of lesions chemically-induced in rodents, such as hyperplasia, dysplasia, low- and high-grade tumours, CIS and invasive urothelial carcinoma are similar to those observed in humans (39).

Experimentally induced urinary bladder tumours. Three models are currently available for inducing urinary bladder tumours: chemically-induced, genetically-engineered, and transplantable (xenograft and syngeneic animals) (Figure 2) (40). A wide range of compounds are described as urinary bladder carcinogens, but of all, BBN is the most frequently used chemical carcinogen (41). However, it is possible to induce urinary bladder cancer with FANFT and N-Methyl-N-nitrosourea (MNU). The selection of each of these agents is made according to the animal facilities and aims of the experimental work (42). The xenograft model is the most routinely used transplantable model and BBN is the carcinogen most frequently applied to induce bladder tumours.

Advantages and Disadvantages of In Vitro and In Vivo Models

As yet, there is not an ideal experimental model for urinary bladder cancer study since both in vitro and in vivo models have limitations. However, with the information obtained from both models, a better understanding of urothelial bladder carcinogenesis is possible. In pre-clinical studies, the antitumour efficacy of a new drug is first evaluated in in vitro models and later in animal models. One of the greatest advantages of in vitro models application is that they offer the possibility to maintain cells in completely controlled environmental conditions, allowing the study of specific cellular and molecular pathways in shortened experimental timescales, being less expensive than animal models and less time-consuming. In contrast, the greatest limitation of this model is that cells growing in vitro are not the exact dissociated replicates of their in vivo counterparts. The use of monolayer cell cultures is usually restricted to a single or at most two cell types. Tumours are composed not only of neoplastic cells but also of stroma and inflammatory cells, which gives a tumour a three-dimensional structure, interacting and influencing its growth (33). The impossibility of tumour angiogenesis and metastasis studies can be considered as limitations of in vitro studies, since these are complex processes with many different mechanisms involved. It is, therefore, clearly difficult to perform in vitro assays which totally simulate these processes and only a combination of methods will be able to provide a clear picture (43). In vitro studies can also provide important information concerning the parameters of pharmacodynamics. To better-understand pharmacokinetics, it is necessary to use in vivo models, since these models offer the best approach for effectively combining and interpreting the major determinants of drug kinetics across species (44). Likewise, in vitro studies do not predict the adverse effects of drugs (45).

For this reason, in vivo models remain important: they preserve the three-dimensional tumour structure with cell-cell interactions and allow for pharmacokinetic and toxicity evaluation of the compounds. Significant limitations of in vivo studies include the necessity for animal facilities, they are also more time consuming, and involve high involved (40). The advantages and disadvantages of in vitro and in vivo models, as well as their possible applications are summarized in Figure 3.

In Vitro Studies to Assess the Efficacy of Antineoplastic and Other Drugs

In the past thirty years, more than 40 studies were conducted in order to evaluate the activity of antineoplastic drugs, making use of several human urinary bladder cancer cell lines, as well as a wide range of methodologies (Table II). It is clearly perceptible that out of the 40 different urinary bladder cancer cell lines used, the T24 muscle-invasive cell line is the one most employed, followed by the HT1376, RT112 and RT4 cell lines. Currently, there is a broad range of methodologies available to assess the in vitro efficacy of drugs, but assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic, flow cytometry and western blot are regularly used. In vitro models have already provided the basis for study of the activity of many antineoplastic drugs. However, alkylating drugs, namely cisplatin and MMC, as well as anti-metabolite drugs, such as gemcitabine, are among the ones most investigated, whether in isolation or combination therapy. Other antineoplastic drugs with different mechanisms of action have also been analyzed, examples are inhibitors of the mammalian target of rapamycin (mTOR) (rapamycin, everolimus), topoisomerase II (epirubicin, doxorubicin, etoposide) and of mitotic spindle formation (paclitaxel, vincristine, vinorelbine). Many of these drugs already tested in vitro (approximately 26) have progressed to clinical studies of urinary bladder cancer. Nevertheless, none of them demonstrated superior efficacy when compared to the drugs currently used in urinary bladder cancer treatment, which is why none of them have been approved as a new therapy.

Figure 2.
Figure 2.

Possible animal models for inducing urinary bladder cancer development in rodents.

Through analysing Table III it is clear that non-antineoplastic drugs have also been studied using human urinary bladder cancer cell lines. Similarly to what happens with antineoplastic drugs, T24 and MTT remain the most used urinary bladder cancer cell line and the most frequent methodology applied, respectively. More than 20 compounds classified as non-antineoplastic drugs were tested, being in the majority non-steroidal anti-inflammatory drugs (NSAIDs). However, very few of these drugs have advanced to clinical studies.

Rodent urinary bladder cancer cell lines are used to assess the efficacy of antineoplastic and other drugs. The mouse MBT-2 and the rat AY-27 urinary bladder cancer cell lines are widely employed (Table IV).

In Vivo Studies to Assess the Efficacy of Antineoplastic and Other Drugs

As previously stated, in vivo models can be used to evaluate drug efficacy. As shown in Table V, in the last twenty years since chemical carcinogens were discovered, more than 25 studies were carried out with rats and mice to analyze antineoplastic drug efficacy in urinary bladder tumours, chemically-induced or implanted. The chemical induction of urinary bladder tumours is commonly implemented using the carcinogen BBN, and for tumour implantation, rodent (MB49, MBT-2, AY-27) and human (HT1376, KU-19-19, 5637, RT4, T24, UM-UC-3) urinary bladder cancer cell lines may be used. Immunotherapy with BCG, in isolation or combined with other drugs, has been one of the therapeutic approaches most extensively investigated in rodent models of urinary bladder cancer. Similarly to in vitro studies, in in vivo models, the use of NSAIDs and other drugs are common, using both chemically-induced and implanted urinary bladder tumours. We verify that the association of two or more drugs is frequent and histopathology and immunohistochemistry are commonly carried out, the expression of Ki-67, proliferating cell nuclear antigen (PCNA), tumour protein 53 (p53), cyclin, cyclo-oxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule (CD31) being widely evaluated on experimental models of urinary bladder cancer. In order to complement the information obtained from the investigation, many studies evaluate the activity of the same drug in both in vivo and in vitro models (Table V and Table VI). None of the drugs tested in vivo, not tested in vitro has advanced to clinical trials, these drugs did not eradicate tumours but only restricted their growth.

Figure 3.
Figure 3.

Advantages, disadvantages and applications of in vitro and in vivo models.

Figure 4.
Figure 4.

Different methodologies to assess antineoplastic drug activity. MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; XTT: 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide; CCK-8: Cell Counting Kit-8; SRB: sulforhodamine B; PI staining: propidium iodide; MTS: (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium); BrdU: 5-bromo-2’-deoxyuridine; MiCK: micro-culture kinetic; PCR: polymerase chain reaction; RT-PCR: reverse transcriptase-PCR; qPCR: quantitative-PCR; TBARs: thiobarbituric acid reactive substances; ELISA: enzyme-linked immunosorbent assay; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling; FTH-SAENTA: 5’-S-{2-(1-[(fluorescein-5-yl)thioureido]-hexanamido)ethyl}-6-N-(4-nitrobenzyl)-5’-thioadenosine; FBA: filter-binding assay; MDC: monodansylcadaverine staining; SEAP: secreted alkaline phosphatase; siRNA: small-interfering RNA; WST: water soluble tetrazolium; SDS-Page: sodium dodecyl sulfate polyacrylamide gel electrophoresis; DAPI: 4’,6-diamidino-2-phenylindole.

Rodent models are particularly valuable for defining the molecular pathways participating in urothelial cell transformation and disease progression, for identifying modifier genes that affect penetrance of the manipulated genes, and for testing various therapeutic and preventive approaches.

Methodologies for Assessing Drug Activity

The use of reliable methodologies to determine and quantify the efficacy of several drugs facilitates the selection of promising candidate drugs for clinical trials (32). As shown in Figure 4, over the years, several methodologies have been developed and used to evaluate the efficacy of different drugs in in vitro and in vivo models. Tests for cytotoxicity and cellular growth inhibition are the oldest and most commonly used assays (43). For in vitro experiments, it should be borne in mind that if a substance leads to a reduced number of viable cells in comparison to the untreated cells after the incubation period, this can be due to the death of some cells, but without affecting growth of another sub-population, or to a general deceleration of growth but survival of all cells. Thus, several assays have been established to measure not only the viable cell number, but also to differentiate between the arrest of growth and cytotoxicity (43). The earliest test methods introduced the use of MTT, and 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), and are based on cellular metabolism. The reduction of these colourless tetrazolium salts into coloured products is correlated with the number of viable cells. However, these assays do not differentiate between the growth arrest and cell death. Thus, it is necessary to additionally scrutinize the number of dead cells, commonly analyzed by microscopic analysis (trypan blue) or flow cytometry (propidium iodide). Other methods commonly applied for measuring cell growth are based on the incorporation of thymidine analogues, such as the 3[H]thymidine and the 5-bromo-2’-deoxyuridine (BrdU) incorporation assays (43). However, even if a drug is effective, this evidence does not necessarily translate into efficacy, we can only see an effect for which our assay was specifically designed. If a substance gives good results when tested, it does not necessarily mean that this substance will be effective (43, 46). Taking this into consideration, it is absolutely necessary to establish guidelines for performing in vitro studies in order to create a basic framework with good predictive proprieties (43, 45).

Conclusion

In the present article, we have reviewed experimental data related to the investigation of antineoplastic drugs for urinary bladder cancer, highlighting the use of in vitro and in vivo models. Used for many decades, well-established in vitro and in vivo models have been available for experimental evaluation of new antineoplastic drugs, providing invaluable pharmacological and toxicological data that may predict for the clinical efficacy of new compounds.

View this table:
Table II.

In vitro studies using human urinary bladder cancer cell lines to assess the efficacy of antineoplastic drugs.

View this table:
Table III.

In vitro studies using human urinary bladder cancer cell lines to assess the efficacy of other drugs.

View this table:
Table IV.

In vitro studies using mouse and rat urinary bladder cancer cell lines to assess the efficacy of antineoplastic and other drugs.

Standard cell culture studies are widely used to delineate the biological, chemical and molecular cues of living cells. Urinary bladder cancer cell lines established from human tumours of different stages and grades allow us to understand the heterogeneous response observed for the same drug between different patients. However, three-dimensional models that recapitulate the tumour microenvironment remain essential. In vivo models overcome this in vitro drawback. The development and optimization of reliable, sensitive and reproducible methodologies are indispensable tools for assessing the in vitro and in vivo efficacy of novel antineoplastic drugs.

View this table:
Table V.

In vivo studies to assess the efficacy of antineoplastic drugs.

From this review, we conclude that to date, more than 50 drugs have been tested on urinary bladder cancer, with BCG, cisplatin, gemcitabine and MMC being the most common, in isolation or applied simultaneously with other drugs, in in vitro or in vivo models. Nowadays, combination therapy is particularly important since the actions of target-based drugs may be supplemented or potentiated by other drugs. This therapeutic approach is increasingly used in experimental models.

Novel targeted-therapies are needed to further improve the chemotherapy efficacy of urinary bladder cancer treatment. Some of the drugs evaluated and described in this article have been shown to be promising in the treatment of this disease. Currently, drugs targeting angiogenesis are promising. Therapeutic investigations should be continued, with the development of new drugs, as well as of targeted therapies to improve treatment results for bladder cancer.

View this table:
Table VI.

In vivo studies to assess the efficacy of other drugs.

Acknowledgements

This study was supported by a grant from the Fundação para a Ciência e Tecnologia, Ministério da Educação, Portugal, grant number SFRH/BD/47612/2008 and by FCT Pest-OE/AGR/UI0772/2011 unity.

  • Received January 21, 2013.
  • Revision received March 7, 2013.
  • Accepted March 7, 2013.

References

  1. ↵
    1. Siegel R,
    2. Naishadham D,
    3. Jemal A
    : Cancer statistics, 2012. CA Cancer J Clin 62(1): 10-29, 2012.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Rassouli FB,
    2. Matin MM,
    3. Iranshahi M,
    4. Bahrami AR,
    5. Behravan J,
    6. Mollazadeh S,
    7. Neshati V,
    8. Kalalinia F
    : Investigating the enhancement of cisplatin cytotoxicity on 5637 cells by combination with mogoltacin. Toxicol In Vitro 25(2): 469-474, 2011.
    OpenUrlPubMed
  3. ↵
    1. Sexton WJ,
    2. Wiegand LR,
    3. Correa JJ,
    4. Politis C,
    5. Dickinson SI,
    6. Kang LC
    : Bladder cancer: a review of non-muscle invasive disease. Cancer Control 17(4): 256-268, 2010.
    OpenUrlPubMed
  4. ↵
    1. Colombel M,
    2. Soloway M,
    3. Akaza H,
    4. Bohle A,
    5. Palou J,
    6. Buckley R,
    7. Lamm D,
    8. Brausi M,
    9. Witjes J,
    10. Persad R
    : Epidemiology, staging, grading, and risk stratification of bladder cancer. Eur Urol Suppl 7: 618-626, 2008.
    OpenUrl
  5. ↵
    1. van Rhijn BW,
    2. Burger M,
    3. Lotan Y,
    4. Solsona E,
    5. Stief CG,
    6. Sylvester RJ,
    7. Witjes JA,
    8. Zlotta AR
    : Recurrence and progression of disease in non-muscle-invasive bladder cancer: From epidemiology to treatment strategy. Eur Urol 56(3): 430-442, 2009.
    OpenUrlCrossRefPubMed
  6. ↵
    1. Abdulamir AS,
    2. Hafidh RR,
    3. Kadhim HS,
    4. Abubakar F
    : Tumor markers of bladder cancer: The schistosomal bladder tumors versus non-schistosomal bladder tumors. J Exp Clin Cancer Res 28(1): 27-40, 2009.
    OpenUrlPubMed
  7. ↵
    1. Tanaka MF,
    2. Sonpavde G
    : Diagnosis and management of urothelial carcinoma of the bladder. Postgrad Med 123(3): 43-55, 2011.
    OpenUrlPubMed
  8. ↵
    1. Botelho MC,
    2. Machado JC,
    3. Brindley PJ,
    4. Correia da Costa JM
    : Targeting molecular signaling pathways of Schistosoma haemotobium infection in bladder cancer. Virulence 2(4): 267-279, 2011.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Eble J,
    2. Sauter G,
    3. Epstein J,
    4. Sesterhenn I
    (eds.): World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of the Urinary and Male Genital Organs, ed. IARCPress. Lyon. pp. 90-158, 2004.
  10. ↵
    1. Cote RJ,
    2. Datar RH
    : Therapeutic approaches to bladder cancer: Identifying targets and mechanisms. Crit Rev Oncol Hematol Suppl 46: S67-S83, 2003.
    OpenUrl
  11. ↵
    1. Palou J,
    2. Sylvester RJ,
    3. Faba OR,
    4. Parada R,
    5. Pena JA,
    6. Algaba F,
    7. Villavicencio H
    : Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guerin. Eur Urol 62(1): 118-125, 2012.
    OpenUrlCrossRefPubMed
  12. ↵
    1. Pasin E,
    2. Josephson DY,
    3. Mitra AP,
    4. Cote RJ,
    5. Stein JP
    : Superficial bladder cancer: an update on etiology, molecular development, classification, and natural history. Rev Urol 10(1): 31-43, 2008.
    OpenUrlPubMed
    1. Palmeira C,
    2. Lameiras C,
    3. Amaro T,
    4. Lima L,
    5. Koch A,
    6. Lopes C,
    7. Oliveira PA,
    8. Santos L
    : CIS is a surrogate marker of genetic instability and field carcinogenesis in the urothelial mucosa. Urol Oncol 29(2): 205-211, 2011.
    OpenUrlPubMed
  14. ↵
    1. Babjuk M,
    2. Oosterlinck W,
    3. Sylvester R,
    4. Kaasinen E,
    5. Bohle A,
    6. Palou-Redorta J
    : EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 54(2): 303-314, 2008.
    OpenUrlCrossRefPubMed
  15. ↵
    1. Kirkali Z,
    2. Chan T,
    3. Manoharan M,
    4. Algaba F,
    5. Busch C,
    6. Cheng L,
    7. Kiemeney L,
    8. Kriegmair M,
    9. Montironi R,
    10. Murphy WM,
    11. Sesterhenn IA,
    12. Tachibana M,
    13. Weider J
    : Bladder cancer: Epidemiology, staging and grading, and diagnosis. Urology 66: 4-34, 2005.
    OpenUrlCrossRefPubMed
  16. ↵
    1. Wirth M,
    2. Plattner VE,
    3. Gabor F
    : Strategies to improve drug delivery in bladder cancer therapy. Expert Opin Drug Deliv 6(7): 727-744, 2009.
    OpenUrlPubMed
  17. ↵
    1. Brausi M,
    2. Collette L,
    3. Kurth K,
    4. van der Meijden AP,
    5. Oosterlinck W,
    6. Witjes JA,
    7. Newling D,
    8. Bouffioux C,
    9. Sylvester RJ
    : Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: A combined analysis of seven EORTC studies. Eur Urol 41(5): 523-531, 2002.
    OpenUrlCrossRefPubMed
  18. ↵
    1. Morales A,
    2. Eidinger D,
    3. Bruce AW
    : Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 116(2): 180-183, 1976.
    OpenUrlCrossRefPubMed
  19. ↵
    1. Lamm DL
    : Complications of bacillus Calmette-Guerin immunotherapy. Urol Clin North Am 19(3): 565-572, 1992.
    OpenUrlPubMed
  20. ↵
    1. van der Meijden AP,
    2. Sylvester RJ,
    3. Oosterlinck W,
    4. Hoeltl W,
    5. Bono AV
    : Maintenance Bacillus Calmette-Guerin for Ta T1 bladder tumors is not associated with increased toxicity: Results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial. Eur Urol 44(4): 429-434, 2003.
    OpenUrlCrossRefPubMed
  21. ↵
    1. Sylvester RJ,
    2. Oosterlinck W,
    3. van der Meijden AP
    : A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: A meta-analysis of published results of randomized clinical trials. J Urol 171: 2186-2190, 2004.
    OpenUrlCrossRefPubMed
  22. ↵
    1. Ismaili N,
    2. Amzerin M,
    3. Flechon A
    : Chemotherapy in advanced bladder cancer: Current status and future. J Hematol Oncol 4: 35-45, 2011.
    OpenUrlCrossRefPubMed
  23. ↵
    1. Loehrer PJS,
    2. Einhorn LH,
    3. Elson PJ,
    4. Crawford ED,
    5. Kuebler P,
    6. Tannock I,
    7. Raghavan D,
    8. Stuart-Harris R,
    9. Sarosdy MF,
    10. Lowe BA,
    11. Blumenstein B,
    12. Trump D
    : A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study. J Clin Oncol 10(7): 1066-1073, 1992.
    OpenUrlAbstract
  24. ↵
    1. Bellmunt J,
    2. Albiol S,
    3. de Olano AR,
    4. Pujadas J,
    5. Maroto P
    : Gemcitabine in the treatment of advanced transitional cell carcinoma of the urothelium. Ann Oncol Suppl 5: 113-117, 2006.
    OpenUrl
  25. ↵
    1. Masters JRW,
    2. Hepburn PJ
    : Human bladder cancer in vitro drug sensitivities: Range and stability in long-term culture. Br J Cancer 54: 131-135, 1986.
    OpenUrlPubMed
  26. ↵
    1. Gabriel U,
    2. Bolenz C,
    3. Michel MS
    : Experimental models for therapeutic studies of transitional cell carcinoma. Anticancer Res 27: 3163-3171, 2007.
    OpenUrlAbstract/FREE Full Text
  27. ↵
    1. Rigby CC,
    2. Franks LM
    : A human tissue culture cell line from a transitional cell tumour of the urinary bladder: growth, chromosone pattern and ultrastructure. Br J Cancer 24(4): 746-754, 1970.
    OpenUrlCrossRefPubMed
  28. ↵
    1. Toyoshima K,
    2. Ito N,
    3. Hiasa Y,
    4. Kamamoto Y,
    5. Makiura S
    : Tissue culture of urinary bladder tumor induced in a rat by N-Butyl-N-(-4-hydroxybutyl)nitrosamine: Establishment of cell line, Nara Bladder Tumor II. J Natl Cancer Inst 47(5): 979-985, 1971.
    OpenUrlCrossRefPubMed
  29. ↵
    1. Lavin P,
    2. Koss LG
    : Studies of experimental bladder carcinoma in Fischer 344 female rats. II. Characterization of three cell lines derived from induced urinary bladder carcinomas. J Natl Cancer Inst 46(3): 597-614, 1971.
    OpenUrlCrossRefPubMed
  30. ↵
    1. el-Marjou A,
    2. Delouvee A,
    3. Thiery JP,
    4. Radvanyi F
    : Involvement of epidermal growth factor receptor in chemically induced mouse bladder tumour progression. Carcinogenesis 21(12): 2211-2218, 2000.
    OpenUrlCrossRefPubMed
  31. ↵
    1. Crallan RA,
    2. Georgopoulos NT,
    3. Southgate J
    : Experimental models of human bladder carcinogenesis. Carcinogenesis 27(3): 374-381, 2006.
    OpenUrlCrossRefPubMed
  32. ↵
    1. Zips D,
    2. Thames HD,
    3. Baumann M
    : New anticancer agents: In vitro and in vivo evaluation. In Vivo 19(1): 1-7, 2005.
    OpenUrlAbstract/FREE Full Text
  33. ↵
    1. Varley CL,
    2. Southgate J
    : Organotypic and 3D reconstructed cultures of the human bladder and urinary tract. Methods Mol Biol 695: 197-211, 2011.
    OpenUrlPubMed
  34. ↵
    1. Chang SG,
    2. Jung JC,
    3. Rho YS,
    4. Huh JS,
    5. Kim JI,
    6. Hoffman RM
    : Efficacy of the platinum analog [Pt(cis-dach)(DPPE)-2NO3] on histocultured human patient bladder tumors and cancer cell lines. Anticancer Res 16(6B): 3423-3428, 1996.
    OpenUrlPubMed
  35. ↵
    1. Kunz-Schughart LA,
    2. Kreutz M,
    3. Knuechel R
    : Multicellular spheroids: a three-dimensional in vitro culture system to study tumour biology. Int J Exp Pathol 79(1): 1-23, 1998.
    OpenUrlCrossRefPubMed
  36. ↵
    1. Burgués JP,
    2. Gómez L,
    3. Pontones JL,
    4. Vera CD,
    5. Jiménez-Cruz JF,
    6. Ozonas M
    : A chemosensitivity test for superficial bladder cancer based on three-dimensional culture of tumour spheroids. Eur Urol 51(4): 962-969, 2007.
    OpenUrlPubMed
  37. ↵
    1. Wessler S
    : Introduction: What is a model? In: Animal Models of Thrombosis and Hemorrhagic Disease. Bethesda. pp. XI, 1976.
  38. ↵
    1. Oliveira PA,
    2. Colaco A,
    3. De la Cruz PL,
    4. Lopes C
    : Experimental bladder carcinogenesis rodent models. Exp Oncol 28(1): 2-11, 2006.
    OpenUrlPubMed
  39. ↵
    1. Palmeira C,
    2. Oliveira PA,
    3. Lameiras C,
    4. Amaro T,
    5. Silva VM,
    6. Lopes C,
    7. Santos L
    : Biological similarities between murine chemical-induced and natural human bladder carcinogenesis. Oncol Lett 1(2): 373-377, 2010.
    OpenUrlPubMed
  40. ↵
    1. Arentsen HC,
    2. Hendricksen K,
    3. Oosterwijk E,
    4. Witjes JA
    : Experimental rat bladder urothelial cell carcinoma models. World J Urol 27(3): 313-317, 2009.
    OpenUrlPubMed
  41. ↵
    1. Vasconcelos-Nobrega C,
    2. Colaco A,
    3. Lopes C,
    4. Oliveira PA
    : BBN as an urothelial carcinogen. In Vivo 26(4): 727-739, 2012.
    OpenUrlAbstract/FREE Full Text
  42. ↵
    1. Oliveira PA,
    2. Colaco A,
    3. Chaves R,
    4. Guedes-Pinto H,
    5. De-La-Cruz PL,
    6. Lopes C
    : Chemical carcinogenesis. An Acad Bras Cienc 79(4): 593-616, 2007.
    OpenUrlCrossRefPubMed
  43. ↵
    1. Drell TLt,
    2. Zanker KS,
    3. Entschladen F
    : Translational research in oncology: The need of additional in vitro preclinical testing methods for new drugs. Curr Pharm Des 18(23): 3416-3420, 2012.
    OpenUrlPubMed
  44. ↵
    1. Mager DE,
    2. Woo S,
    3. Jusko WJ
    : Scaling pharmacodynamics from in vitro and preclinical animal studies to humans. Drug Metab Pharmacokinet 24(1): 16-24, 2009.
    OpenUrlCrossRefPubMed
  45. ↵
    1. Kooijman M,
    2. van Meer PJ,
    3. Moors EH,
    4. Schellekens H
    : Thirty years of preclinical safety evaluation of biopharmaceuticals: Did scientific progress lead to appropriate regulatory guidance? Expert Opin Drug Saf 11(5): 797-801, 2012.
    OpenUrlPubMed
  46. ↵
    1. Berger J
    : The age of biomedicine: Current trends in traditional subjects. J Appl Biomed 9: 57-61, 2011.
    OpenUrl
    1. Fogh J
    : Cultivation, characterization, and identification of human tumor cells with emphasis on kidney, testis, and bladder tumors. Natl Cancer Inst Monogr 49: 5-9, 1978.
    OpenUrl
    1. Marshall CJ,
    2. Franks LM,
    3. Carbonell AW
    : Markers of neoplastic transformation in epithelial cell lines derived from human carcinomas. J Natl Cancer Inst 58(6): 1743-1751, 1977.
    OpenUrlCrossRefPubMed
    1. Rasheed S,
    2. Gardner MB,
    3. Rongey RW,
    4. Nelson-Rees WA,
    5. Arnstein P
    : Human bladder carcinoma: characterization of two new tumor cell lines and search for tumor viruses. J Natl Cancer Inst 58(4): 881-890, 1977.
    OpenUrlCrossRefPubMed
    1. Bubenik J,
    2. Baresova M,
    3. Viklicky V,
    4. Jakoubkova J,
    5. Sainerova H,
    6. Donner J
    : Established cell line of urinary bladder carcinoma (T24) containing tumour-specific antigen. Int J Cancer 11(3): 765-773, 1973.
    OpenUrlCrossRefPubMed
    1. Tachibana M,
    2. Miyakawa A,
    3. Tazaki H,
    4. Nakamura K,
    5. Kubo A,
    6. Hata J,
    7. Nishi T,
    8. Amano Y
    : Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor. Cancer Res 55(15): 3438-3443, 1995.
    OpenUrlAbstract/FREE Full Text
    1. Zoli W,
    2. Ricotti L,
    3. Tesei A,
    4. Ulivi P,
    5. Gasperi Campani A,
    6. Fabbri F,
    7. Gunelli R,
    8. Frassineti GL,
    9. Amadori D
    : Schedule-dependent cytotoxic interaction between epidoxorubicin and gemcitabine in human bladder cancer cells in vitro. Clin Cancer Res 10(4): 1500-1507, 2004.
    OpenUrlAbstract/FREE Full Text
    1. Evans DR,
    2. Irwin RJ,
    3. Havre PA,
    4. Bouchard JG,
    5. Kato T,
    6. Prout GR
    : The activity of the pyrimidine biosynthetic pathway in MGH-U1 transitional carcinoma cells grown in tissue culture. J Urol 117(6): 712-719, 1997.
    OpenUrl
    1. Bruch J,
    2. Wohr G,
    3. Bruderlein S,
    4. Barbi G,
    5. Wolter H,
    6. Dixkens C,
    7. Mattfeldt T,
    8. Moller P,
    9. Paiss T,
    10. Hautmann R,
    11. Vogel W,
    12. Hameister H
    : Detailed marker chromosome analysis in cell line U-BLC1, established from transitional cell carcinoma of the bladder. Int J Cancer 80(6): 903-910, 1999.
    OpenUrlCrossRefPubMed
    1. Pratsinis H,
    2. Saetta A,
    3. Gagos S,
    4. Davaris P
    : Isolation and characterization of a novel bladder cancer cell line: Inhibition by epidermal growth factor. In Vitro Cell Dev Biol Anim 34(9): 722-728, 1998.
    OpenUrlPubMed
    1. Cattan N,
    2. Rochet N,
    3. Mazeau C,
    4. Zanghellini E,
    5. Mari B,
    6. Chauzy C,
    7. Stora de Novion H,
    8. Amiel J,
    9. Lagrange JL,
    10. Rossi B,
    11. Gioanni J
    : Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors. Br J Cancer 85(9): 1412-1417, 2001.
    OpenUrlCrossRefPubMed
    1. Nayak SK,
    2. O'Toole C,
    3. Price ZH
    : A cell line from an anaplastic transitional cell carcinoma of human urinary bladder. Br J Cancer 35(2): 142-151, 1977.
    OpenUrlCrossRefPubMed
    1. Grossman HB,
    2. Wedemeyer G,
    3. Ren L
    : UM-UC-1 and UM-UC-2: characterization of two new human transitional cell carcinoma lines. J Urol 132(4): 834-837, 1984.
    OpenUrlPubMed
    1. Grossman HB,
    2. Wedemeyer G,
    3. Ren L,
    4. Wilson GN,
    5. Cox B
    : Improved growth of human urothelial carcinoma cell cultures. J Urol 136(4): 953-959, 1986.
    OpenUrlPubMed
    1. Nouri AM,
    2. Bergbaum A,
    3. Lederer E,
    4. Crosby D,
    5. Shamsa A,
    6. Oliver RT
    : Paired tumour infiltrating lymphocyte (TIL) and tumour cell line from bladder cancer: A new approach to study tumour immunology in vitro. Eur J Cancer 27(5): 608-612, 1991.
    OpenUrlPubMed
    1. Elliott AY,
    2. Bronson DL,
    3. Stein N,
    4. Fraley EE
    : In vitro cultivation of epithelial cells derived from tumors of the human urinary tract. Cancer Res 36: 365-369, 1976.
    OpenUrlAbstract/FREE Full Text
    1. Cohen SM,
    2. Yang JP,
    3. Jacobs JB,
    4. Arai M,
    5. Fukushima S,
    6. Friedell GH
    : Transplantation and cell culture of rat urinary bladder carcinoma. Invest Urol 19(3): 136-141, 1981.
    OpenUrlPubMed
    1. Wu WS,
    2. Yin KZ,
    3. Han YM
    : Establishment and study of a transpatable bladder transitional cell carcinoma model in T739 inbred mice. Chinese cancer Clinic 23: 751-756, 1996.
    OpenUrl
    1. Williams PD,
    2. Murphy GP
    : Experimental bladder tumor induction, propagation, and therapy. Urology 8(1): 39-42, 1976.
    OpenUrlPubMed
    1. Popert RJ,
    2. Masters JR,
    3. Coptcoat M,
    4. Zupi G
    : Relative cytotoxicities of adriamycin and epirubicin in combination with lonidamine against human bladder cancer cell lines. Urol Res 22(6): 367-372, 1995.
    OpenUrlPubMed
    1. Winquist E,
    2. Ernst DS,
    3. Jonker D,
    4. Moore MJ,
    5. Segal R,
    6. Lockwood G,
    7. Rodgers A
    : Phase II trial of pegylated-liposomal doxorubicin in the treatment of locally advanced unresectable or metastatic transitional cell carcinoma of the urothelial tract. Eur J Cancer 39(13): 1866-1871, 2003.
    OpenUrlPubMed
    1. Jones WG,
    2. Sokal MP,
    3. Ostrowski MJ,
    4. Newling DW
    : A phase II study of epirubicin in advanced transitional cell bladder cancer. The Yorkshire Urological Cancer Research Group. Clin Oncol 5(1): 25-29, 1993.
    OpenUrl
    1. Giannotti P,
    2. Ambrogi F,
    3. Ciottoli GB
    : Lonidamine plus adriamycin versus adriamycin alone in the adjuvant treatment of recurrent papillary carcinomas of the urinary bladder. Oncology 41: 104-107, 1984.
    OpenUrlPubMed
    1. Kato T,
    2. Bilim V,
    3. Yuuki K,
    4. Naito S,
    5. Yamanobe T,
    6. Nagaoka A,
    7. Yano I,
    8. Akaza H,
    9. Tomita Y
    : Bacillus Calmette-Guerin and BCG cell wall skeleton suppressed viability of bladder cancer cells in vitro. Anticancer Res 30(10): 4089-4096, 2010.
    OpenUrlAbstract/FREE Full Text
    1. Brosman SA
    : Experience with Bacillus Calmette-Guerin in patients with superficial bladder carcinoma. J Urol 128(1): 27-30, 1982.
    OpenUrlPubMed
    1. Kosugi M,
    2. Miyajima A,
    3. Kikuchi E,
    4. Kosaka T,
    5. Horiguchi Y,
    6. Murai M
    : Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer. Hum Cell 20(1): 1-9, 2007.
    OpenUrlCrossRefPubMed
    1. Joly F,
    2. Houede N,
    3. Noal S,
    4. Chevreau C,
    5. Priou F,
    6. Chinet-Charrot P,
    7. Rolland F,
    8. Flechon A,
    9. Henry-Amar M,
    10. Culine S
    : Do patients with advanced urothelial carcinoma benefit from weekly paclitaxel chemotherapy? A GETUG phase II study. Clin Genitourin Cancer 7(2): 28-33, 2009.
    OpenUrlCrossRefPubMed
    1. Konstantakou EG,
    2. Voutsinas GE,
    3. Karkoulis PK,
    4. Aravantinos G,
    5. Margaritis LH,
    6. Stravopodis DJ
    : Human bladder cancer cells undergo cisplatin-induced apoptosis that is associated with p53-dependent and p53-independent responses. Int J Oncol 35(2): 401-416, 2009.
    OpenUrlPubMed
    1. Miyake H,
    2. Hara I,
    3. Gohji K,
    4. Yoshimura K,
    5. Arakawa S,
    6. Kamidono S
    : Expression of basic fibroblast growth factor is associated with resistance to cisplatin in a human bladder cancer cell line. Cancer Lett 123(2): 121-126, 1998.
    OpenUrlCrossRefPubMed
    1. Coppin CM,
    2. Gospodarowicz MK,
    3. James K,
    4. Tannock IF,
    5. Zee B,
    6. Carson J,
    7. Pater J,
    8. Sullivan LD
    : Improved local control of invasive bladder cancer by concurrent cisplatin and preoperative or definitive radiation. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 14(11): 2901-2907, 1996.
    OpenUrlAbstract
    1. Parris CN,
    2. Walker MC,
    3. Masters JR,
    4. Arlett CF
    : Inherent sensitivity and induced resistance to chemotherapeutic drugs and irradiation in human cancer cell lines: relationship to mutation frequencies. Cancer Res 50(23): 7513-7518, 1990.
    OpenUrlAbstract/FREE Full Text
    1. Sonpavde G,
    2. Jian W,
    3. Liu H,
    4. Wu MF,
    5. Shen SS,
    6. Lerner SP
    : Sunitinib malate is active against human urothelial carcinoma and enhances the activity of cisplatin in a preclinical model. Urol Oncol 27(4): 391-399, 2009.
    OpenUrlCrossRefPubMed
    1. Gallagher DJ,
    2. Milowsky MI,
    3. Gerst SR,
    4. Ishill N,
    5. Riches J,
    6. Regazzi A,
    7. Boyle MG,
    8. Trout A,
    9. Flaherty AM,
    10. Bajorin DF
    : Phase II study of sunitinib in patients with metastatic urothelial cancer. J Clin Oncol 28(8): 1373-1379, 2010.
    OpenUrlAbstract/FREE Full Text
    1. Mizutani Y,
    2. Nakao M,
    3. Ogawa O,
    4. Yoshida O,
    5. Bonavida B,
    6. Miki T
    : Enhanced sensitivity of bladder cancer cells to tumor necrosis factor related apoptosis inducing ligand mediated apoptosis by cisplatin and carboplatin. J Urol 165(1): 263-270, 2001.
    OpenUrlCrossRefPubMed
    1. Gallo Rolania FJ,
    2. Beneitez Alvarez M,
    3. Roa Luzuriaga M,
    4. de Blas Gomez V
    : Use of systemic carboplatin in superficial tumors of the bladder. Preliminary phase II study (toxicity). Arch Esp Urol 42(7): 652-654, 1989.
    OpenUrlPubMed
    1. Erlichman C,
    2. Vidgen D,
    3. Wu A
    : Antineoplastic drug cytotoxicity in a human bladder cancer cell line: implications for intravesical chemotherapy. Urol Res 15(1): 13-16, 1987.
    OpenUrlPubMed
    1. Kuroiwa T,
    2. Naito S,
    3. Hasuo K,
    4. Kishikawa T,
    5. Masuda K,
    6. Kumazawa J
    : Phase II study of a new combined primary chemotherapy regimen, intravenous methotrexate and vincristine and intraarterial adriamycin and cisplatin, for locally advanced urinary bladder cancer: Preliminary results. Cancer Chemother Pharmacol 35(5): 357-363, 1995.
    OpenUrlPubMed
    1. Huan SD,
    2. Aitken SE,
    3. Stewart DJ
    : A phase II study of 5-fluorouracil and high dose folinic acid in cisplatin-refractory metastatic bladder cancer. Ann Oncol 6(8): 836-837, 1995.
    OpenUrlPubMed
    1. Walker MC,
    2. Parris CN,
    3. Masters JR
    : Differential sensitivities of human testicular and bladder tumor cell lines to chemotherapeutic drugs. J Natl Cancer Inst 79(2): 213-216, 1987.
    OpenUrlCrossRefPubMed
    1. Sengor F,
    2. Beysel M,
    3. Erdogan K,
    4. Erol A,
    5. Tuzluoglu D
    : Intravesical epirubicin in the prophylaxis of superficial bladder cancer. Int Urol Nephrol 28(2): 201-206, 1996.
    OpenUrlPubMed
    1. Nakajima K,
    2. Hisazumi H,
    3. Kumaki O,
    4. Ueki O
    : Inhibition of cell growth by irradiation in combination with hyperthermia or anticancer drugs. Acta Radiol Oncol 22(6): 487-492, 1983.
    OpenUrlPubMed
    1. Turner AG,
    2. Durrant KR,
    3. Malpas JS
    : A trial of bleomycin versus adriamycin in advanced carcinoma of the bladder. Br J Urol 51(2): 121-124, 1979.
    OpenUrlCrossRefPubMed
    1. Yoon CY,
    2. Lee JS,
    3. Kim BS,
    4. Jeong SJ,
    5. Hong SK,
    6. Byun SS,
    7. Lee SE
    : Sunitinib malate synergistically potentiates antitumor effect of gemcitabine in human bladder cancer cells. Korean J Urol 52(1): 55-63, 2011.
    OpenUrlCrossRefPubMed
    1. Mohanty NK,
    2. Nayak RL,
    3. Vasudeva P,
    4. Arora RP
    : Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder - our experience. Urol Oncol 26(6): 616-619, 2008.
    OpenUrlCrossRefPubMed
    1. Pinto-Leite R,
    2. Arantes-Rodrigues R,
    3. Palmeira C,
    4. Colaço B,
    5. Lopes C,
    6. Colaço A,
    7. Costa C,
    8. Silva VM,
    9. Oliveira P,
    10. Santos L
    : Everolimus combined with cisplatin has a potential role in treatment of urothelial bladder cancer. Biomed Pharmacother doi: 10.1016/j.biopha.2012.11.007, 2012.
    1. Maruyama T,
    2. Yamamoto S,
    3. Qiu J,
    4. Ueda Y,
    5. Suzuki T,
    6. Nojima M,
    7. Shima H
    : Apoptosis of bladder cancer by sodium butyrate and cisplatin. J Infect Chemother 18(3): 288-295, 2012.
    OpenUrlPubMed
    1. Kassouf W,
    2. Luongo T,
    3. Brown G,
    4. Adam L,
    5. Dinney CP
    : Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer. J Urol 176(2): 787-792, 2006.
    OpenUrlCrossRefPubMed
    1. McKiernan JM,
    2. Masson P,
    3. Murphy AM,
    4. Goetzl M,
    5. Olsson CA,
    6. Petrylak DP,
    7. Desai M,
    8. Benson MC
    : Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy. J Clin Oncol 24(19): 3075-3080, 2006.
    OpenUrlAbstract/FREE Full Text
    1. Philips GK,
    2. Halabi S,
    3. Sanford BL,
    4. Bajorin D,
    5. Small EJ
    : A phase II trial of cisplatin (C), gemcitabine (G) and gefitinib for advanced urothelial tract carcinoma: Results of Cancer and Leukemia Group B (CALGB) 90102. Ann Oncol 20(6): 1074-1079, 2009.
    OpenUrlCrossRefPubMed
    1. Pauwels O,
    2. Gozy M,
    3. Van Houtte P,
    4. Pasteels JL,
    5. Atassi G,
    6. Kiss R
    : Cross resistance and collateral sensitivity between cytotoxic drugs and radiation in two human bladder cell lines. Radiother Oncol 39(1): 81-86, 1996.
    OpenUrlPubMed
    1. Bonfil RD,
    2. Gonzalez AD,
    3. Siguelboim D,
    4. Cuello Carrion FD,
    5. Ciocca DR,
    6. Villaronga A,
    7. Metz L,
    8. Mosso F,
    9. Fayad E,
    10. Reale M,
    11. Schmilovich AJ
    : Immunohistochemical analysis of Ki-67, p21WAF1/CIP1 and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial. BJU Int 88(4): 425-431, 2001.
    OpenUrlPubMed
    1. Chresta CM,
    2. Masters JR,
    3. Hickman JA
    : Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high BAX:BCL-2 ratio. Cancer Res 56(8): 1834-1841, 1996.
    OpenUrlAbstract/FREE Full Text
    1. Suzuki K
    : Phase II study of etoposide (VP-16-213) in genitourinary tumors. VP-16-213 Genitourinary Study Group. Gan To Kagaku Ryoho 13(9): 2772-2779, 1986 (in Japanese).
    OpenUrlPubMed
    1. Chiong E,
    2. Lee IL,
    3. Dadbin A,
    4. Sabichi AL,
    5. Harris L,
    6. Urbauer D,
    7. McConkey DJ,
    8. Dickstein RJ,
    9. Cheng T,
    10. Grossman HB
    : Effects of mTOR inhibitor everolimus (RAD001) on bladder cancer cells. Clin Cancer Res 17(9): 2863-2873, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Vasconcelos-Nobrega C,
    2. Pinto-Leite R,
    3. Arantes-Rodrigues R,
    4. Ferreira R,
    5. Brochado P,
    6. Cardoso ML,
    7. Palmeira C,
    8. Salvador A,
    9. Guedes-Teixeira CI,
    10. Colaco A,
    11. Palomino LF,
    12. Lopes C,
    13. Santos L,
    14. Oliveira PA
    : In vivo and in vitro effects of RAD001 on bladder cancer. Urol Oncol doi: 10.1016/j.urolonc.2011.11.002, 2011.
    1. Rexer H
    : Second line AUO (Working Group Urological Oncology) study AB 35/09 on metastasized urothelial carcinoma. Phase II study with RAD001 in combination with paclitaxel for patients with metastasized urothelial carcinoma of the urinary bladder after failure of platinum-based chemotherapy (CRAD001). Urologe A 50(11): 1464-1465, 2011.
    OpenUrlPubMed
    1. Piazza GA,
    2. Thompson WJ,
    3. Pamukcu R,
    4. Alila HW,
    5. Whitehead CM,
    6. Liu L,
    7. Fetter JR,
    8. Gresh WEJ,
    9. Klein-Szanto AJ,
    10. Farnell DR,
    11. Eto I,
    12. Grubbs CJ
    : Exisulind, a novel proapoptotic drug, inhibits rat urinary bladder tumorigenesis. Cancer Res 61(10): 3961-3968, 2001.
    OpenUrlAbstract/FREE Full Text
    1. Neri B,
    2. Doni L,
    3. Fulignati C,
    4. Gemelli MT,
    5. Turrini M,
    6. Di Cello V,
    7. Dominici A,
    8. Mottola A,
    9. Raugei A,
    10. Ponchietti R,
    11. Cini G
    : Gemcitabine plus epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: A phase II. Anticancer Res 22(5): 2981-2984, 2002.
    OpenUrlPubMed
    1. Engeler DS,
    2. Scandella E,
    3. Ludewig B,
    4. Schmid HP
    : Ciprofloxacin and epirubicin synergistically induce apoptosis in human urothelial cancer cell lines. Urol Int 88(3): 343-349, 2012.
    OpenUrlPubMed
    1. Ebisuno S,
    2. Inagaki T,
    3. Kohjimoto Y,
    4. Ohkawa T
    : The cytotoxic effect of fleroxacin and ciprofloxacin on transitional cell carcinoma in vitro. Cancer 80(12): 2263-2267, 1997.
    OpenUrlCrossRefPubMed
    1. Nishikawa T,
    2. Kohjimoto Y,
    3. Nishihata M,
    4. Ebisuno S,
    5. Hara I
    : Synergistic antitumor effects of fleroxacin with 5-fluorouracil in vitro and in vivo for bladder cancer cell lines. Urology 74(6): 1370-1376, 2009.
    OpenUrlCrossRefPubMed
    1. Gazzaniga P,
    2. Silvestri I,
    3. Gradilone A,
    4. Scarpa S,
    5. Morrone S,
    6. Gandini O,
    7. Gianni W,
    8. Frati L,
    9. Agliano AM
    : Gemcitabine-induced apoptosis in 5637 cell line: an in vitro model for high-risk superficial bladder cancer. Anticancer Drugs 18(2): 179-185, 2007.
    OpenUrlCrossRefPubMed
    1. Gunelli R,
    2. Bercovich E,
    3. Nanni O,
    4. Ballardini M,
    5. Frassineti GL,
    6. Giovannini N,
    7. Fiori M,
    8. Pasquini E,
    9. Ulivi P,
    10. Pappagallo GL,
    11. Silvestrini R,
    12. Zoli W
    : Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: A translational study. Br J Cancer 97(11): 1499-1504, 2007.
    OpenUrlPubMed
    1. Damaraju S,
    2. Damaraju VL,
    3. Mowles D,
    4. Sawyer MB,
    5. Damaraju S,
    6. Cass CE
    : Cytotoxic activity of gemcitabine in cultured cell lines derived from histologically different types of bladder cancer: Role of thymidine kinase 2. Biochem Pharmacol 79(1): 21-29, 2009.
    OpenUrlPubMed
    1. Mey V,
    2. Giovannetti E,
    3. De Braud F,
    4. Nannizzi S,
    5. Curigliano G,
    6. Verweij F,
    7. De Cobelli O,
    8. Pece S,
    9. Del Tacca M,
    10. Danesi R
    : In vitro synergistic cytotoxicity of gemcitabine and pemetrexed and pharmacogenetic evaluation of response to gemcitabine in bladder cancer patients. Br J Cancer 95(3): 289-297, 2006.
    OpenUrlCrossRefPubMed
    1. Galsky MD,
    2. Mironov S,
    3. Iasonos A,
    4. Scattergood J,
    5. Boyle MG,
    6. Bajorin DF
    : Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma. Invest New Drugs 25(3): 265-270, 2007.
    OpenUrlCrossRefPubMed
    1. Perabo FG,
    2. Lindner H,
    3. Schmidt D,
    4. Huebner D,
    5. Blatter J,
    6. Fimmers R,
    7. Muller SC,
    8. Albers P
    : Preclinical evaluation of gemcitabine/paclitaxel-interactions in human bladder cancer lines. Anticancer Res 23(6C): 4805-4814, 2003.
    OpenUrlPubMed
    1. Pinto-Leite R,
    2. Arantes-Rodrigues R,
    3. Palmeira C,
    4. Gaivao I,
    5. Cardoso ML,
    6. Colaco A,
    7. Santos L,
    8. Oliveira P
    : Everolimus enhances gemcitabine-induced cytotoxicity in bladder cancer cell lines. J Toxicol Environ Health A 75(13-15): 788-799, 2012.
    OpenUrlCrossRefPubMed
    1. Zhang C,
    2. Cai TY,
    3. Zhu H,
    4. Yang LQ,
    5. Jiang H,
    6. Dong XW,
    7. Hu YZ,
    8. Lin NM,
    9. He QJ,
    10. Yang B
    : Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1. Mol Cancer Ther 10(7): 1264-1275, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Kamat AM,
    2. Karashima T,
    3. Davis DW,
    4. Lashinger L,
    5. Bar-Eli M,
    6. Millikan R,
    7. Shen Y,
    8. Dinney CP,
    9. McConkey DJ
    : The proteasome inhibitor bortezomib synergizes with gemcitabine to block the growth of human 253JB-V bladder tumors in vivo. Mol Cancer Ther 3(3): 279-290, 2004.
    OpenUrlAbstract/FREE Full Text
    1. Rosenberg JE,
    2. Halabi S,
    3. Sanford BL,
    4. Himelstein AL,
    5. Atkins JN,
    6. Hohl RJ,
    7. Millard F,
    8. Bajorin DF,
    9. Small EJ
    : Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207. Ann Oncol 19(5): 946-950, 2008.
    OpenUrlCrossRefPubMed
    1. Ma Y,
    2. Yu WD,
    3. Trump DL,
    4. Johnson CS
    : 1,25D3 Enhances antitumor activity of gemcitabine and cisplatin in human bladder cancer models. Cancer 116(13): 3294-3303, 2010.
    OpenUrlCrossRefPubMed
    1. McHugh LA,
    2. Kriajevska M,
    3. Mellon JK,
    4. Griffiths TR
    : Combined treatment of bladder cancer cell lines with lapatinib and varying chemotherapy regimens-evidence of schedule-dependent synergy. Urology 69(2): 390-394, 2007.
    OpenUrlCrossRefPubMed
    1. Wulfing C,
    2. Machiels JP,
    3. Richel DJ,
    4. Grimm MO,
    5. Treiber U,
    6. De Groot MR,
    7. Beuzeboc P,
    8. Parikh R,
    9. Petavy F,
    10. El-Hariry IA
    : A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer 115(13): 2881-2890, 2009.
    OpenUrlCrossRefPubMed
    1. van der Heijden AG,
    2. Jansen CF,
    3. Verhaegh G,
    4. O'Donnell M A,
    5. Schalken JA,
    6. Witjes JA
    : The effect of hyperthermia on mitomycin-C induced cytotoxicity in four human bladder cancer cell lines. Eur Urol 46(5): 670-674, 2004.
    OpenUrlCrossRefPubMed
    1. Addeo R,
    2. Caraglia M,
    3. Bellini S,
    4. Abbruzzese A,
    5. Vincenzi B,
    6. Montella L,
    7. Miragliuolo A,
    8. Guarrasi R,
    9. Lanna M,
    10. Cennamo G,
    11. Faiola V,
    12. Del Prete S
    : Randomized phase III trial on gemcitabine versus mitomycin in recurrent superficial bladder cancer: Evaluation of efficacy and tolerance. J Clin Oncol 28(4): 543-548, 2010.
    OpenUrlAbstract/FREE Full Text
    1. Okamoto E,
    2. Kinne RK,
    3. Sokeland J
    : Interferons modify in vitro proliferation of human bladder transitional cell carcinoma in the presence of doxorubicin and mitomycin C. J Urol 156(4): 1492-1495, 1996.
    OpenUrlCrossRefPubMed
    1. van der Heijden AG,
    2. Verhaegh G,
    3. Jansen CF,
    4. Schalken JA,
    5. Witjes JA
    : Effect of hyperthermia on the cytotoxicity of four chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: An in vitro study. J Urol 173(4): 1375-1380, 2005.
    OpenUrlCrossRefPubMed
    1. Knuchel R,
    2. Hofstadter F,
    3. Jenkins WE,
    4. Masters JR
    : Sensitivities of monolayers and spheroids of the human bladder cancer cell line MGH-U1 to the drugs used for intravesical chemotherapy. Cancer Res 49(6): 1397-1401, 1989.
    OpenUrlAbstract/FREE Full Text
    1. Masters JR,
    2. McDermott BJ,
    3. Harland S,
    4. Bibby MC,
    5. Loadman PM
    : ThioTEPA pharmacokinetics during intravesical chemotherapy: The influence of dose and volume of instillate on systemic uptake and dose rate to the tumour. Cancer Chemother Pharmacol 38(1): 59-64, 1996.
    OpenUrlCrossRefPubMed
    1. Mackie SJ,
    2. Sharma DM,
    3. Cooper AJ,
    4. Harris NM,
    5. Lwaleed BA
    : Meglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: In vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin. Prostaglandins Leukot Essent Fatty Acids 75(6): 367-373, 2006.
    OpenUrlPubMed
    1. Seay TM,
    2. Peretsman SJ,
    3. Dixon PS
    : Inhibition of human transitional cell carcinoma in vitro proliferation by fluoroquinolone antibiotics. J Urol 155(2): 757-762, 1996.
    OpenUrlCrossRefPubMed
    1. Colombel M,
    2. Saint F,
    3. Chopin D,
    4. Malavaud B,
    5. Nicolas L,
    6. Rischmann P
    : The effect of ofloxacin on Bacillus Calmette-Guerin-induced toxicity in patients with superficial bladder cancer: Results of a randomized, prospective, double-blind, placebo controlled, multicenter study. J Urol 176(3): 935-939, 2006.
    OpenUrlCrossRefPubMed
    1. Vicari L,
    2. Musumeci T,
    3. Giannone I,
    4. Adamo L,
    5. Conticello C,
    6. De Maria R,
    7. Pignatello R,
    8. Puglisi G,
    9. Gulisano M
    : Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity. BMC Cancer 8: 212, 2008.
    OpenUrlPubMed
    1. Cubedo E,
    2. Cordeu L,
    3. Bandres E,
    4. Rebollo A,
    5. Malumbres R,
    6. Sanmartin C,
    7. Font M,
    8. Palop JA,
    9. Gacia-Foncillas J
    : New symmetrical quinazoline derivatives selectively induce apoptosis in human cancer cells. Cancer Biol Ther 5(7): 850-859, 2006.
    OpenUrlCrossRefPubMed
    1. Fechner G,
    2. Classen K,
    3. Schmidt D,
    4. Hauser S,
    5. Muller SC
    : Rapamycin inhibits in vitro growth and release of angiogenetic factors in human bladder cancer. Urology 73(3): 665-668, 2009.
    OpenUrlCrossRefPubMed
    1. Pinto-Leite R,
    2. Botelho P,
    3. Ribeiro E,
    4. Oliveira PA,
    5. Santos L
    : Effect of sirolimus on urinary bladder cancer T24 cell line. J Exp Clin Cancer Res 28: 3, 2009.
    OpenUrlPubMed
    1. Abramjuk C,
    2. Bueschges M,
    3. Schnorr J,
    4. Jung K,
    5. Staack A,
    6. Lein M
    : Divergent effects of taurolidine as potential anti-neoplastic agent: Inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo. Oncol Rep 22(2): 409-414, 2009.
    OpenUrlPubMed
    1. Simoens C,
    2. Lardon F,
    3. Pauwels B,
    4. De Pooter CM,
    5. Lambrechts HA,
    6. Pattyn GG,
    7. Breillout F,
    8. Vermorken JB
    : Comparative study of the radiosensitizing and cell cycle effects of vinflunine and vinorelbine, in vitro. BMC Cancer 8: 65, 2008.
    OpenUrlCrossRefPubMed
    1. Lee SJ,
    2. Cho YH,
    3. Park K,
    4. Kim EJ,
    5. Kang BS,
    6. Jung KH,
    7. Kim CH,
    8. Kim WJ,
    9. Moon SK
    : Inhibitory effects of the aqueous extract of Magnolia officinalis on the responses of human urinary bladder cancer 5637 cells in vitro and mouse urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in vivo. Phytother Res 23(1): 20-27, 2009.
    OpenUrlPubMed
    1. Bhattacharya A,
    2. Tang L,
    3. Li Y,
    4. Geng F,
    5. Paonessa JD,
    6. Chen SC,
    7. Wong MK,
    8. Zhang Y
    : Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis 31(2): 281-286, 2010.
    OpenUrlCrossRefPubMed
    1. Fabbri F,
    2. Brigliadori G,
    3. Ulivi P,
    4. Tesei A,
    5. Vannini I,
    6. Rosetti M,
    7. Bravaccini S,
    8. Amadori D,
    9. Bolla M,
    10. Zoli W
    : Pro-apoptotic effect of a nitric oxide-donating NSAID, NCX 4040, on bladder carcinoma cells. Apoptosis 10(5): 1095-1103, 2005.
    OpenUrlCrossRefPubMed
    1. Khwaja F,
    2. Allen J,
    3. Lynch J,
    4. Andrews P,
    5. Djakiew D
    : Ibuprofen inhibits survival of bladder cancer cells by induced expression of the p75NTR tumor suppressor protein. Cancer Res 64(17): 6207-6213, 2004.
    OpenUrlAbstract/FREE Full Text
    1. Andrews P,
    2. Zhao X,
    3. Allen J,
    4. Li F,
    5. Chang M
    : A comparison of the effectiveness of selected non-steroidal anti-inflammatory drugs and their derivatives against cancer cells in vitro. Cancer Chemother Pharmacol 61(2): 203-214, 2008.
    OpenUrlPubMed
    1. Roomi MW,
    2. Ivanov V,
    3. Kalinovsky T,
    4. Niedzwiecki A,
    5. Rath M
    : Antitumor effect of ascorbic acid, lysine, proline, arginine, and green tea extract on bladder cancer cell line T-24. Int J Urol 13(4): 415-419, 2006.
    OpenUrlPubMed
    1. Schwartz L,
    2. Abolhassani M,
    3. Guais A,
    4. Sanders E,
    5. Steyaert JM,
    6. Campion F,
    7. Israel M
    : A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: Preliminary results. Oncol Rep 23(5): 1407-1416, 2010.
    OpenUrlPubMed
    1. Hong SH,
    2. Choi YH
    : Bufalin induces apoptosis through activation of both the intrinsic and extrinsic pathways in human bladder cancer cells. Oncol Rep 27(1): 114-120, 2012.
    OpenUrlPubMed
    1. Zhang L,
    2. Chen W,
    3. Li X
    : A novel anticancer effect of butein: Inhibition of invasion through the ERK1/2 and NF-kappa B signaling pathways in bladder cancer cells. FEBS Lett 582(13): 1821-1828, 2008.
    OpenUrlCrossRefPubMed
    1. Beck TP,
    2. Kirsh EJ,
    3. Chmura SJ,
    4. Kovar DA,
    5. Chung T,
    6. Rinker-Schaeffer CW,
    7. Stadler WM
    : In vitro evaluation of calphostin C as a novel agent for photodynamic therapy of bladder cancer. Urology 54(3): 573-577, 1999.
    OpenUrlPubMed
    1. Farivar-Mohseni H,
    2. Kandzari SJ,
    3. Zaslau S,
    4. Riggs DR,
    5. Jackson BJ,
    6. McFadden DW
    : Synergistic effects of Cox-1 and -2 inhibition on bladder and prostate cancer in vitro. Am J Surg 188(5): 505-510, 2004.
    OpenUrlCrossRefPubMed
    1. Mohseni H,
    2. Zaslau S,
    3. McFadden D,
    4. Riggs DR,
    5. Jackson BJ,
    6. Kandzari S
    : COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer in vitro. J Surg Res 119(2): 138-142, 2004.
    OpenUrlCrossRefPubMed
    1. Dhawan D,
    2. Jeffreys AB,
    3. Zheng R,
    4. Stewart JC,
    5. Knapp DW
    : Cyclooxygenase-2 dependent and independent antitumor effects induced by celecoxib in urinary bladder cancer cells. Mol Cancer Ther 7(4): 897-904, 2008.
    OpenUrlAbstract/FREE Full Text
    1. Gee JR,
    2. Burmeister CB,
    3. Havighurst TC,
    4. Kim K
    : Cyclin-mediated G1 arrest by celecoxib differs in low versus high-grade bladder cancer. Anticancer Res 29(10): 3769-3775, 2009.
    OpenUrlAbstract/FREE Full Text
    1. Sabichi AL,
    2. Lee JJ,
    3. Grossman HB,
    4. Liu S,
    5. Richmond E,
    6. Czerniak BA,
    7. De la Cerda J,
    8. Eagle C,
    9. Viner JL,
    10. Palmer JL,
    11. Lerner SP
    : A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle-invasive bladder cancer. Cancer Prev Res 4(10): 1580-1589, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Gee J,
    2. Lee IL,
    3. Jendiroba D,
    4. Fischer SM,
    5. Grossman HB,
    6. Sabichi AL
    : Selective cyclooxygenase-2 inhibitors inhibit growth and induce apoptosis of bladder cancer. Oncol Rep 15(2): 471-477, 2006.
    OpenUrlPubMed
    1. Adhim Z,
    2. Matsuoka T,
    3. Bito T,
    4. Shigemura K,
    5. Lee KM,
    6. Kawabata M,
    7. Fujisawa M,
    8. Nibu K,
    9. Shirakawa T
    : In vitro and in vivo inhibitory effect of three COX-2 inhibitors and epithelial-to-mesenchymal transition in human bladder cancer cell lines. Br J Cancer 105(3): 393-402, 2011.
    OpenUrlCrossRefPubMed
    1. Mohammed SI,
    2. Dhawan D,
    3. Abraham S,
    4. Snyder PW,
    5. Waters DJ,
    6. Craig BA,
    7. Lu M,
    8. Wu L,
    9. Zheng R,
    10. Stewart J,
    11. Knapp DW
    : Cyclooxygenase inhibitors in urinary bladder cancer: In vitro and in vivo effects. Mol Cancer Ther 5(2): 329-336, 2006.
    OpenUrlAbstract/FREE Full Text
    1. Plissonnier ML,
    2. Fauconnet S,
    3. Bittard H,
    4. Lascombe I
    : The antidiabetic drug ciglitazone induces high-grade bladder cancer cell apoptosis through the up-regulation of TRAIL. PLoS One 6(12): e28354, 2011.
    OpenUrlPubMed
    1. Shen CH,
    2. Shee JJ,
    3. Wu JY,
    4. Lin YW,
    5. Wu JD,
    6. Liu YW
    : Combretastatin A-4 inhibits cell growth and metastasis in bladder cancer cells and retards tumour growth in a murine orthotopic bladder tumour model. Br J Pharmacol 160(8): 2008-2027, 2010.
    OpenUrlCrossRefPubMed
    1. Sun M,
    2. Yang Y,
    3. Li H,
    4. Su B,
    5. Lu Y,
    6. Wei Q,
    7. Fan T
    : The effect of curcumin on bladder cancer cell line EJ in vitro. Zhong Yao Cai 27(11): 848-850, 2004 (in Chinese).
    OpenUrlPubMed
    1. Tian B,
    2. Wang Z,
    3. Zhao Y,
    4. Wang D,
    5. Li Y,
    6. Ma L,
    7. Li X,
    8. Li J,
    9. Xiao N,
    10. Tian J,
    11. Rodriguez R
    : Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model. Cancer Lett 264(2): 299-308, 2008.
    OpenUrlCrossRefPubMed
    1. Cheng AL,
    2. Hsu CH,
    3. Lin JK,
    4. Hsu MM,
    5. Ho YF,
    6. Shen TS,
    7. Ko JY,
    8. Lin JT,
    9. Lin BR,
    10. Ming-Shiang W,
    11. Yu HS,
    12. Jee SH,
    13. Chen GS,
    14. Chen TM,
    15. Chen CA,
    16. Lai MK,
    17. Pu YS,
    18. Pan MH,
    19. Wang YJ,
    20. Tsai CC,
    21. Hsieh CY
    : Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4B): 2895-2900, 2001.
    OpenUrlPubMed
    1. Pichu S,
    2. Krishnamoorthy S,
    3. Shishkov A,
    4. Zhang B,
    5. McCue P,
    6. Ponnappa BC
    : Knockdown of Ki-67 by dicer-substrate small-interfering RNA sensitizes bladder cancer cells to curcumin-induced tumor inhibition. PLoS One 7(11): e48567, 2012.
    OpenUrlPubMed
    1. Okamoto A,
    2. Shirakawa T,
    3. Bito T,
    4. Shigemura K,
    5. Hamada K,
    6. Gotoh A,
    7. Fujisawa M,
    8. Kawabata M
    : Etodolac, a selective cyclooxygenase-2 inhibitor, induces upregulation of E-cadherin and has antitumor effect on human bladder cancer cells in vitro and in vivo. Urology 71(1): 156-160, 2008.
    OpenUrlCrossRefPubMed
    1. Speers AG,
    2. Lwaleed BA,
    3. Featherstone JM,
    4. Sallis BJ,
    5. Cooper AJ
    : Furosemide reverses multidrug resistance status in bladder cancer cells in vitro. J Clin Pathol 59(9): 912-915, 2006.
    OpenUrlAbstract/FREE Full Text
    1. Azuma H,
    2. Takahara S,
    3. Horie S,
    4. Muto S,
    5. Otsuki Y,
    6. Katsuoka Y
    : Induction of apoptosis in human bladder cancer cells in vitro and in vivo caused by FTY720 treatment. J Urol 169(6): 2372-2377, 2003.
    OpenUrlCrossRefPubMed
    1. Swellam T,
    2. Miyanaga N,
    3. Onozawa M,
    4. Hattori K,
    5. Kawai K,
    6. Shimazui T,
    7. Akaza H
    : Antineoplastic activity of honey in an experimental bladder cancer implantation model: In vivo and in vitro studies. Int J Urol 10(4): 213-219, 2003.
    OpenUrlCrossRefPubMed
    1. Liu H,
    2. Schwartz MJ,
    3. Hwang DH,
    4. Scherr DS
    : Tumour growth inhibition by an imidazoquinoline is associated with c-Myc down-regulation in urothelial cell carcinoma. BJU Int 101(7): 894-901, 2008.
    OpenUrlPubMed
    1. Arantes-Rodrigues R,
    2. Pinto-Leite R,
    3. Fidalgo-Gonçalves L,
    4. Gaivão I,
    5. Colaço A,
    6. Oliveira P,
    7. Santos L
    : Meloxicam synergistically enhances the in vitro effects of sunitinib malate on bladder cancer cells. J Appl Biomed 11: 79-92, 2013.
    OpenUrl
    1. Sun F,
    2. Zheng XY,
    3. Ye J,
    4. Wu TT,
    5. Wang J,
    6. Chen W
    : Potential anticancer activity of myricetin in human T24 bladder cancer cells both in vitro and in vivo. Nutr Cancer 64(4): 599-606, 2012.
    OpenUrlCrossRefPubMed
    1. Sato K,
    2. Yuasa T,
    3. Nogawa M,
    4. Kimura S,
    5. Segawa H,
    6. Yokota A,
    7. Maekawa T
    : A third-generation bisphosphonate, minodronic acid (YM529), successfully prevented the growth of bladder cancer in vitro and in vivo. Br J Cancer 95(10): 1354-1361, 2006.
    OpenUrlCrossRefPubMed
    1. Huguenin S,
    2. Vacherot F,
    3. Kheuang L,
    4. Fleury-Feith J,
    5. Jaurand MC,
    6. Bolla M,
    7. Riffaud JP,
    8. Chopin DK
    : Antiproliferative effect of nitrosulindac (NCX 1102), a new nitric oxide-donating non-steroidal anti-inflammatory drug, on human bladder carcinoma cell lines. Mol Cancer Ther 3(3): 291-298, 2004.
    OpenUrlAbstract/FREE Full Text
    1. Smakman N,
    2. Schaap N,
    3. Snijckers CM,
    4. Borel Rinkes IH,
    5. Kranenburg O
    : NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation. Urology 66(2): 434-440, 2005.
    OpenUrlCrossRefPubMed
    1. Ou TT,
    2. Wu CH,
    3. Hsu JD,
    4. Chyau CC,
    5. Lee HJ,
    6. Wang CJ
    : Paeonia lactiflora Pall inhibits bladder cancer growth involving phosphorylation of Chk2 in vitro and in vivo. J Ethnopharmacol 135(1): 162-172, 2011.
    OpenUrlCrossRefPubMed
    1. Cheng G,
    2. Xie L
    : Parthenolide induces apoptosis and cell cycle arrest of human 5637 bladder cancer cells in vitro. Molecules 16(8): 6758-6768, 2011.
    OpenUrlCrossRefPubMed
    1. Bai Y,
    2. Mao QQ,
    3. Qin J,
    4. Zheng XY,
    5. Wang YB,
    6. Yang K,
    7. Shen HF,
    8. Xie LP
    : Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo. Cancer Sci 101(2): 488-493, 2010.
    OpenUrlCrossRefPubMed
    1. Stocco B,
    2. Toledo K,
    3. Salvador M,
    4. Paulo M,
    5. Koyama N,
    6. Torqueti Toloi MR
    : Dose-dependent effect of resveratrol on bladder cancer cells: Chemoprevention and oxidative stress. Maturitas 72(1): 72-78, 2012.
    OpenUrlCrossRefPubMed
    1. Yeh CC,
    2. Kuo HM,
    3. Li TM,
    4. Lin JP,
    5. Yu FS,
    6. Lu HF,
    7. Chung JG,
    8. Yang JS
    : Shikonin-induced apoptosis involves caspase-3 activity in a human bladder cancer cell line (T24). In Vivo 21(6): 1011-1019, 2007.
    OpenUrlAbstract/FREE Full Text
    1. Zeng J,
    2. Sun Y,
    3. Wu K,
    4. Li L,
    5. Zhang G,
    6. Yang Z,
    7. Wang Z,
    8. Zhang D,
    9. Xue Y,
    10. Chen Y,
    11. Zhu G,
    12. Wang X,
    13. He D
    : Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria. Mol Cancer Ther 10(1): 104-116, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Ikemoto S,
    2. Sugimura K,
    3. Yoshida N,
    4. Yasumoto R,
    5. Wada S,
    6. Yamamoto K,
    7. Kishimoto T
    : Antitumor effects of Scutellariae radix and its components baicalein, baicalin, and wogonin on bladder cancer cell lines. Urology 55(6): 951-955, 2000.
    OpenUrlCrossRefPubMed
    1. Torti SV,
    2. Torti FM,
    3. Whitman SP,
    4. Brechbiel MW,
    5. Park G,
    6. Planalp RP
    : Tumor cell cytotoxicity of a novel metal chelator. Blood 92(4): 1384-1389, 1998.
    OpenUrlAbstract/FREE Full Text
    1. Yang S,
    2. Chen J,
    3. Guo Z,
    4. Xu XM,
    5. Wang L,
    6. Pei XF,
    7. Yang J,
    8. Underhill CB,
    9. Zhang L
    : Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther 2(1): 65-72, 2003.
    OpenUrlAbstract/FREE Full Text
    1. Zheng QY,
    2. Jin FS,
    3. Yao C,
    4. Zhang T,
    5. Zhang GH,
    6. Ai X
    : Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells. Biochem Biophys Res Commun 419(4): 741-747, 2012.
    OpenUrlCrossRefPubMed
    1. Konety BR,
    2. Lavelle JP,
    3. Pirtskalaishvili G,
    4. Dhir R,
    5. Meyers SA,
    6. Nguyen TS,
    7. Hershberger P,
    8. Shurin MR,
    9. Johnson CS,
    10. Trump DL,
    11. Zeidel ML,
    12. Getzenberg RH
    : Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo. J Urol 165(1): 253-258, 2001.
    OpenUrlCrossRefPubMed
    1. Yang HJ,
    2. Yen MC,
    3. Lin CC,
    4. Lin CM,
    5. Chen YL,
    6. Weng TY,
    7. Huang TT,
    8. Wu CL,
    9. Lai MD
    : A combination of the metabolic enzyme inhibitor APO866 and the immune adjuvant L-1-methyl tryptophan induces additive antitumor activity. Exp Biol Med 235(7): 869-876, 2010.
    OpenUrlCrossRefPubMed
    1. Sonoda T,
    2. Sugimura K,
    3. Ikemoto S,
    4. Kawashima H,
    5. Nakatani T
    : Significance of target cell infection and natural killer cells in the antitumor effects of Bacillus Calmette-Guerin in murine bladder cancer. Oncol Rep 17(6): 1469-1474, 2007.
    OpenUrlPubMed
    1. Lee JS,
    2. Chang JS,
    3. Lee JY,
    4. Kim JA
    : Capsaicin-induced apoptosis and reduced release of reactive oxygen species in MBT-2 murine bladder tumor cells. Arch Pharm Res 27(11): 1147-1153, 2004.
    OpenUrlCrossRefPubMed
    1. Horinaga M,
    2. Fukuyama R,
    3. Iida M,
    4. Yanaihara H,
    5. Nakahira Y,
    6. Nonaka S,
    7. Deguchi N,
    8. Asakura H
    : Enhanced antitumor effect of coincident intravesical gemcitabine plus BCG therapy in an orthotopic bladder cancer model. Urology 76(5): 1267 e1-6, 2010.
    OpenUrlPubMed
    1. Leite KR,
    2. Chade DC,
    3. Sanudo A,
    4. Sakiyama BY,
    5. Batocchio G,
    6. Srougi M
    : Effects of curcumin in an orthotopic murine bladder tumor model. Int Braz J Urol 35(5): 599-606, 2009.
    OpenUrlPubMed
    1. Chen JJ,
    2. Ye ZQ,
    3. Koo MW
    : Growth inhibition and cell cycle arrest effects of epigallocatechin gallate in the NBT-II bladder tumour cell line. BJU Int 93(7): 1082-1086, 2004.
    OpenUrlPubMed
    1. Mossberg AK,
    2. Hou Y,
    3. Svensson M,
    4. Holmqvist B,
    5. Svanborg C
    : HAMLET treatment delays bladder cancer development. J Urol 183(4): 1590-1597, 2010.
    OpenUrlCrossRefPubMed
    1. Selman SH,
    2. Keck RW
    : A comparative study of the inhibiting effects of mitomycin C and polyphenolic catechins on tumor cell implantation/growth in a rat bladder tumor model. J Urol 186(2): 702-706, 2011.
    OpenUrlPubMed
    1. Bhattacharya A,
    2. Li Y,
    3. Geng F,
    4. Munday R,
    5. Zhang Y
    : The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N-allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder cancer. Carcinogenesis 33(2): 394-398, 2012.
    OpenUrlCrossRefPubMed
    1. Ikemoto S,
    2. Sugimura K,
    3. Kuratukuri K,
    4. Nakatani T
    : Antitumor effects of lipoxygenase inhibitors on murine bladder cancer cell line (MBT-2). Anticancer Res 24(2B): 733-736, 2004.
    OpenUrlAbstract/FREE Full Text
    1. Nativ O,
    2. Aronson M,
    3. Medalia O,
    4. Moldavsky T,
    5. Sabo E,
    6. Ringel I,
    7. Kravtsov V
    : Anti-neoplastic activity of paclitaxel on experimental superficial bladder cancer: in vivo and in vitro studies. Int J Cancer 70(3): 297-301, 1997.
    OpenUrlCrossRefPubMed
    1. Garcia Mediero JM,
    2. Ferruelo Alonso A,
    3. Paez Borda A,
    4. Lujan Galan M,
    5. Angulo Cuesta J,
    6. Chiva Robles V,
    7. Berenguer Sanchez A
    : Effect of polyphenols from the Mediterranean diet on proliferation and mediators of in vitro invasiveness of the MB-49 murine bladder cancer cell line. Actas Urol Esp 29(8): 743-749, 2005.
    OpenUrlPubMed
    1. Wu CL,
    2. Ping SY,
    3. Yu CP,
    4. Yu DS
    : Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer. Kaohsiung J Med Sci 28(4): 194-203, 2012.
    OpenUrlPubMed
    1. Hong SH,
    2. Choi YS,
    3. Cho HJ,
    4. Lee JY,
    5. Hwang TK,
    6. Kim SW
    : Induction of apoptosis of bladder cancer cells by zinc-citrate compound. Korean J Urol 53(11): 800-806, 2012.
    OpenUrlPubMed
    1. Yanagisawa T,
    2. Suzuki T,
    3. Kudoh T,
    4. Oh SC
    : Effect of intravesical Bacillus Calmette-Guerin on N-butyl-N-(4-hydroxybutyl)-nitrosamine induced urinary bladder carcinogenesis in rats. Nihon Hinyokika Gakkai Zasshi 85(6): 945-952, 1994 (in Japanese).
    OpenUrlPubMed
    1. Tanaka S,
    2. Kudoh S,
    3. Mollik AU,
    4. Kudoh T,
    5. Kogawa T,
    6. Suzuki T
    : Histological study on intravesical instillation of Bacillus Calmette Guerin (BCG) and adriamycin for BBN-induced bladder tumor in rats. Nihon Hinyokika Gakkai Zasshi 83(3): 368-373, 1992 (in Japanese).
    OpenUrlPubMed
    1. Steinberg GD,
    2. Brendler CB,
    3. Squire RA,
    4. Isaacs JT
    : Experimental intravesical therapy for superficial transitional cell carcinoma in a rat bladder tumor model. J Urol 145(3): 647-653, 1991.
    OpenUrlPubMed
    1. Oliveira PA,
    2. Palmeira C,
    3. Colaco A,
    4. de la Cruz LF,
    5. Lopes C
    : DNA content analysis, expression of Ki-67 and p53 in rat urothelial lesions induced by N-butyl-N-(4-hydroxybutyl) nitrosamine and treated with mitomycin C and Bacillus Calmette-Guerin. Anticancer Res 26(4B): 2995-3004, 2006.
    OpenUrlAbstract/FREE Full Text
    1. Miyazaki J,
    2. Nishiyama H,
    3. Yano I,
    4. Nakaya A,
    5. Kohama H,
    6. Kawai K,
    7. Joraku A,
    8. Nakamura T,
    9. Harashima H,
    10. Akaza H
    : The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder carcinoma. Anticancer Res 31(6): 2065-2071, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Xiao Z,
    2. Hanel E,
    3. Mak A,
    4. Moore RB
    : Antitumor efficacy of intravesical BCG, gemcitabine, interferon-alpha and interleukin-2 as mono- or combination-therapy for bladder cancer in an orthotopic tumor model. Clin Med Insights Oncol 5: 315-323, 2011.
    OpenUrlPubMed
    1. Reis LO,
    2. Ferreira U,
    3. Billis A,
    4. Cagnon VH,
    5. Favaro WJ
    : Anti-angiogenic effects of the superantigen staphylococcal enterotoxin B and Bacillus Calmette-Guerin immunotherapy for nonmuscle invasive bladder cancer. J Urol 187(2): 438-445, 2012.
    OpenUrlPubMed
    1. Kosugi M,
    2. Miyajima A,
    3. Kikuchi E,
    4. Kosaka T,
    5. Horiguchi Y,
    6. Murai M,
    7. Oya M
    : Angiotensin II type 1 receptor antagonist enhances cis-dichlorodiammineplatinum-induced cytotoxicity in mouse xenograft model of bladder cancer. Urology 73(3): 655-660, 2009.
    OpenUrlCrossRefPubMed
    1. Kong C,
    2. Zhu Y,
    3. Sun C,
    4. Li Z,
    5. Sun Z,
    6. Zhang X,
    7. Takanaka I
    : Inhibition of tumor angiogenesis during cisplatin chemotherapy for bladder cancer improves treatment outcome. Urology 65(2): 395-399, 2005.
    OpenUrlCrossRefPubMed
    1. Brocks CP,
    2. Buttner H,
    3. Bohle A
    : Inhibition of tumor implantation by intravesical gemcitabine in a murine model of superficial bladder cancer. J Urol 174(3): 1115-1118, 2005.
    OpenUrlPubMed
    1. Nativ O,
    2. Dalal E,
    3. Laufer M,
    4. Sabo E,
    5. Aronson M
    : Antineoplastic effect of gemcitabine in an animal model of superficial bladder cancer. Urology 64(4): 845-848, 2004.
    OpenUrlPubMed
    1. Vasconcelos-Nobrega C,
    2. Colaco A,
    3. Santos L,
    4. Vala H,
    5. Palomino LF,
    6. Lopes C,
    7. Oliveira PA
    : Experimental study of the anticancer effect of gemcitabine combined with sirolimus on chemically induced urothelial lesions. Anticancer Res 31(5): 1637-1642, 2011.
    OpenUrlAbstract/FREE Full Text
    1. Zhang X,
    2. Jin L,
    3. Takenaka I
    : MVAC chemotherapy-induced apoptosis and p53 alterations in the rat model of bladder cancer. Urology 52(5): 925-931, 1998.
    OpenUrlPubMed
    1. Oliveira PA,
    2. Arantes-Rodrigues R,
    3. Sousa-Diniz C,
    4. Colaco A,
    5. Lourenco L,
    6. De La Cruz LF,
    7. Da Silva VM,
    8. Afonso J,
    9. Lopes C,
    10. Santos L
    : The effects of sirolimus on urothelial lesions chemically induced in ICR mice by BBN. Anticancer Res 29(8): 3221-3226, 2009.
    OpenUrlAbstract/FREE Full Text
    1. Cohen SM,
    2. Zenser TV,
    3. Murasaki G,
    4. Fukushima S,
    5. Mattammal MB,
    6. Rapp NS,
    7. Davis BB
    : Aspirin inhibition of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced lesions of the urinary bladder correlated with inhibition of metabolism by bladder prostaglandin endoperoxide synthetase. Cancer Res 41: 3355-3359, 1981.
    OpenUrlAbstract/FREE Full Text
    1. Klan R,
    2. Knispel HH,
    3. Meier T
    : Acetylsalicylic acid inhibition of N-butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats. J Cancer Res Clin Oncol 119(8): 482-485, 1993.
    OpenUrlCrossRefPubMed
    1. Rao KV,
    2. Detrisac CJ,
    3. Steele VE,
    4. Hawk ET,
    5. Kelloff GJ,
    6. McCormick DL
    : Differential activity of aspirin, ketoprofen and sulindac as cancer chemopreventive agents in the mouse urinary bladder. Carcinogenesis 17(7): 1435-1438, 1996.
    OpenUrlCrossRefPubMed
    1. Grubbs CJ,
    2. Lubet RA,
    3. Koki AT,
    4. Leahy KM,
    5. Masferrer JL,
    6. Steele VE,
    7. Kelloff GJ,
    8. Hill DL,
    9. Seibert K
    : Celecoxib inhibits N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder cancers in male B6D2F1 mice and female Fischer-344 rats. Cancer Res 60(20): 5599-5602, 2000.
    OpenUrlAbstract/FREE Full Text
    1. Parada B,
    2. Sereno J,
    3. Reis F,
    4. Teixeira-Lemos E,
    5. Garrido P,
    6. Pinto AF,
    7. Cunha MF,
    8. Pinto R,
    9. Mota A,
    10. Figueiredo A,
    11. Teixeira F
    : Anti-inflammatory, anti-proliferative and antioxidant profiles of selective cyclooxygenase-2 inhibition as chemoprevention for rat bladder carcinogenesis. Cancer Biol Ther 8(17): 1615-1622, 2009.
    OpenUrlPubMed
    1. Sereno J,
    2. Parada B,
    3. Reis F,
    4. Cunha FX,
    5. Teixeira-Lemos E,
    6. Garrido P,
    7. Pinto R,
    8. Rocha-Pereira P,
    9. Neto P,
    10. Ruivo J,
    11. Rodrigues-Santos P,
    12. Nunes S,
    13. Mota A,
    14. Figueiredo A,
    15. Teixeira F
    : Preventive but not curative efficacy of celecoxib on bladder carcinogenesis in a rat model. Mediators Inflamm 2010: 380937, 2010.
    OpenUrlPubMed
    1. Chihara Y,
    2. Fujimoto K,
    3. Miyake M,
    4. Hiasa Y,
    5. Hirao Y
    : Anti-tumor effect of cimetidine via inhibiting angiogenesis factors in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse and rat bladder carcinogenesis. Oncol Rep 22(1): 23-28, 2009.
    OpenUrlPubMed
    1. Watanabe FT,
    2. Chade DC,
    3. Reis ST,
    4. Piantino C,
    5. Dall' Oglio MF,
    6. Srougi M,
    7. Leite KR
    : Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model. Clinics 66(12): 2121-2124, 2011.
    OpenUrlPubMed
    1. Hattori K,
    2. Iida K,
    3. Joraku A,
    4. Tsukamoto S,
    5. Akaza H,
    6. Oyasu R
    : Chemopreventive effects of cyclooxygenase-2 inhibitor and epidermal growth factor-receptor kinase inhibitor on rat urinary bladder carcinogenesis. BJU Int 97(3): 640-643, 2006.
    OpenUrlCrossRefPubMed
    1. Lubet RA,
    2. Steele VE,
    3. Juliana MM,
    4. Grubbs CJ
    : Screening agents for preventive efficacy in a bladder cancer model: Study design, end points, and gefitinib and naproxen efficacy. J Urol 183(4): 1598-1603, 2010.
    OpenUrlCrossRefPubMed
    1. Henriques A,
    2. Arantes-Rodrigues R,
    3. Teixeira-Guedes CI,
    4. Faustino-Rocha AI,
    5. Pinho-Oliveira J,
    6. Talhada D,
    7. Teixeira JH,
    8. Andrade A,
    9. Colaço B,
    10. Cardoso MN,
    11. Pires MJ,
    12. Ferreira AMVD,
    13. Nunes FM,
    14. Oliveira PA
    : The effects of whole green tea on mouse bladder chemical carcinogenesis. Iran J Basic Med Sci, 2013, In Press.
    1. Lubet RA,
    2. Huebner K,
    3. Fong LY,
    4. Altieri DC,
    5. Steele VE,
    6. Kopelovich L,
    7. Kavanaugh C,
    8. Juliana MM,
    9. Soong SJ,
    10. Grubbs CJ
    : 4-Hydroxybutyl(butyl)nitrosamine-induced urinary bladder cancers in mice: characterization of FHIT and survivin expression and chemopreventive effects of indomethacin. Carcinogenesis 26(3): 571-578, 2005.
    OpenUrlCrossRefPubMed
    1. Holmang S,
    2. Cano M,
    3. Grenabo L,
    4. Hedelin H,
    5. Johansson SL
    : Effect of indomethacin on N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide-induced urinary tract carcinogenesis. Carcinogenesis 16(7): 1493-1498, 1995.
    OpenUrlCrossRefPubMed
    1. Okajima E,
    2. Denda A,
    3. Ozono S,
    4. Takahama M,
    5. Akai H,
    6. Sasaki Y,
    7. Kitayama W,
    8. Wakabayashi K,
    9. Konishi Y
    : Chemopreventive effects of nimesulide, a selective cyclooxygenase-2 inhibitor, on the development of rat urinary bladder carcinomas initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine. Cancer Res 58(14): 3028-3031, 1998.
    OpenUrlAbstract/FREE Full Text
    1. Yu A,
    2. Hashimura T,
    3. Nishio Y,
    4. Kanamaru H,
    5. Fukuzawa S,
    6. Yoshida O
    : Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis. Jpn J Cancer Res 83(9): 944-948, 1992.
    OpenUrlPubMed
    1. Okajima E,
    2. Ozono S,
    3. Endo T,
    4. Majima T,
    5. Tsutsumi M,
    6. Fukuda T,
    7. Akai H,
    8. Denda A,
    9. Hirao Y,
    10. Okajima E,
    11. Nishino H,
    12. Nir Z,
    13. Konishi Y
    : Chemopreventive efficacy of piroxicam administered alone or in combination with lycopene and beta-carotene on the development of rat urinary bladder carcinoma after N-butyl-N-(4-hydroxybutyl)nitrosamine treatment. Jpn J Cancer Res 88(6): 543-552, 1997.
    OpenUrlCrossRef
    1. D'Arca D,
    2. LeNoir J,
    3. Wildemore B,
    4. Gottardo F,
    5. Bragantini E,
    6. Shupp-Byrne D,
    7. Zanesi N,
    8. Fassan M,
    9. Croce CM,
    10. Gomella LG,
    11. Baffa R
    : Prevention of urinary bladder cancer in the FHIT knock-out mouse with rofecoxib, a Cox-2 inhibitor. Urol Oncol 28(2): 189-194, 2010.
    OpenUrlPubMed
    1. Singh RP,
    2. Tyagi A,
    3. Sharma G,
    4. Mohan S,
    5. Agarwal R
    : Oral silibinin inhibits in vivo human bladder tumor xenograft growth involving down-regulation of survivin. Clin Cancer Res 14(1): 300-308, 2008.
    OpenUrlAbstract/FREE Full Text
    1. Tyagi A,
    2. Raina K,
    3. Singh RP,
    4. Gu M,
    5. Agarwal C,
    6. Harrison G,
    7. Glode LM,
    8. Agarwal R
    : Chemopreventive effects of silymarin and silibinin on N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in male ICR mice. Mol Cancer Ther 6: 3248-3255, 2007.
    OpenUrlAbstract/FREE Full Text
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
In Vitro and In Vivo Experimental Models as Tools to Investigate the Efficacy of Antineoplastic Drugs on Urinary Bladder Cancer
REGINA ARANTES-RODRIGUES, AURA COLAÇO, ROSÁRIO PINTO-LEITE, PAULA A. OLIVEIRA
Anticancer Research Apr 2013, 33 (4) 1273-1296;
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords