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Sample records for bladder tumor response

  1. BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses.

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    Lamm, D L; Thor, D E; Winters, W D; Stogdill, V D; Radwin, H M

    1981-07-01

    Fifty-one patients with confirmed bladder cancer have enrolled in a prospective evaluation of BCG immunotherapy. Following resection of existing tumors, patients were stratified according to tumor grade and number of previous recurrences and randomly assigned to control or BCG treatment groups. Immunotherapy consisted of six weekly administrations of Pasteur strain BCG using 120 mg intravesically and 5 mg percutaneously. Immunotherapy side effects were minimal and no patient required postponement of BCG treatments. Eleven control (46%) compared with five (22%) BCG-treated patients had tumor recurrence (P = 0.078, chi 2). Prolongation of the disease-free interval with BCG treatment was significantly at the P = 0.016 level by Wilcoxon analysis. Four control and two BCG-treated patients had multiple recurrences. Comparing total episodes of recurrence, nineteen of 79 (24%) control and eight of 85 (7%) BCG group cystoscopic examinations revealed tumor (P = 0.006, chi 2). Immunologic correlates of response to immunotherapy were not statistically significant since only five BCG-treated patients had tumor recurrence. However, four of these five patients evidenced impaired LIF response to PPD at the time of tumor recurrence, and impairment of skin test reactivity and BCG humoral antibody response were more commonly seen in this subgroup of patients. PMID:7016300

  2. Imaging of urinary bladder tumors

    International Nuclear Information System (INIS)

    Full text: Primary bladder neoplasms account for 2%-6% of all tumors, with urinary bladder cancer ranked as the fourth most common cancer in males. Transitional cell carcinoma (TCC) is the most common subtype of urothelial tumour accounting for approximately 90% of all urothelial cancers. It is typically observed in men aged 50-70 years with history of smoking or occupational exposure to carcinogens. Most urothelial neoplasms are low-grade papillary tumors, with high incidence of recurrence, requires rigorous follow-up but have a relatively good prognosis. Other bladder neoplasm include squamous cell carcinoma accounts for 2%-15% mainly according to geographic location; adenocarcinoma - less than 2% /both occurring in the context of chronic bladder infection and irritation/; mesenchymal tumors in 5%, with the most common examples being rhabdomyosarcoma in children and leiomyosarcoma in adults. More rare mesenchymal tumors include paraganglioma, lymphoma, leiomyoma and solitary fibrous tumor which have no specific typical imaging findings to be differentiated. Multidetector computed tomography urography is an efficient tool for diagnosis and follow-up in patients with transitional cell carcinoma and it can be considered the primary radiologic method for detection, staging and assessment of the entire urothelium regarding the multicentric nature of TCC. MRI is rapidly expanding modality of choice especially in locally staging the tumor and in controversies. Accurate TNM staging is primordial in choosing treatment and prognosis for patients with bladder carcinoma. Correct interpretation and classification of the tumour is helpful for the urologists to determine further management in these cases. The learning objectives of the presentation are: to illustrate the spectrum of CT and MRI findings and to assess their clinical value in patients with transitional cell carcinoma and some other bladder neoplasm; to discuss the TNM staging based on the imaging findings; to be

  3. Inflammatory myofibroblastic tumor of the urinary bladder

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    Yagnik Vipul; Chadha Amit; Chaudhari Sanjay; Patel Keyuri

    2010-01-01

    Inflammatory myofibroblastic tumor (IMT) of bladder is an uncommon benign tumor of bladder, which is of unknown neoplastic potential, characterized by spindle cell proliferation with characteristic fibroinflammatory and pseudosarcomatous appearance. Essential criteria for the diagnosis of IMT are: spindle myoepithelial cell proliferation and lymphocytic infiltrate. Complete surgical resection is the treatment of choice.

  4. Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

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    Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

    1987-04-01

    Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG

  5. Tasquinimod modulates tumor-infiltrating myeloid cells and improves the antitumor immune response to PD-L1 blockade in bladder cancer

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    Nakhlé, Jessica; Pierron, Valérie; Bauchet, Anne-Laure; Plas, Pascale; Thiongane, Amath; Meyer-Losic, Florence; Schmidlin, Fabien

    2016-01-01

    ABSTRACT The infiltration of myeloid cells helps tumors to overcome immune surveillance and imparts resistance to cancer immunotherapy. Thus, strategies to modulate the effects of these immune cells may offer a potential therapeutic benefit. We report here that tasquinimod, a novel immunotherapy which targets S100A9 signaling, reduces the immunosuppressive properties of myeloid cells in preclinical models of bladder cancer (BCa). As single anticancer agent, tasquinimod treatment was effective in preventing early stage tumor growth, but did not achieve a clear antitumor effect in advanced tumors. Investigations of this response revealed that tasquinimod induces an increase in the expression of a negative regulator of T cell activation, Programmed-death-ligand 1 (PD-L1). This markedly weakens its antitumor immunity, yet provokes an “inflamed” milieu rendering tumors more prone to T cell-mediated immune attack by PD-L1 blockade. Interestingly, the combination of tasquinimod with an Anti-PD-L1 antibody enhanced the antitumor immune response in bladder tumors. This combination synergistically modulated tumor-infiltrating myeloid cells, thereby strongly affecting proliferation and activation of effector T cells. Together, our data provide insight into the rational combination of therapies that activate both innate and adaptive immune system, such as the association of S100A9-targeting agents with immune checkpoints inhibitors, to improve the response to cancer immunotherapeutic agents in BCa.

  6. Transurethral en bloc resection of bladder tumors

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    A. G. Martov

    2015-01-01

    Full Text Available Background. The high incidence of recurrent non-muscle-invasive bladder carcinoma (BC necessitates searches for new surgical methods. Objective: to comparatively evaluate the efficiency and safety of en block resection of bladder tumors versus transurethral resection (TUR. Subjects and methods. In January 2010 to June 2013, a total of 292 patients with primary and recurrent bladder tumor stages, cTa-T2, underwent transurethral endoscopic treatment (as TUR at the Unit of Minimally Invasive Urology, Moscow City Clinical Hospital Fifty-Seven. A major portion of these patients were included in the study of the efficiency and safety of en bloc TUR of bladder tumors. The criteria for study inclusion were primary or recurrent non-muscle-invasive bladder tumor measuring 1 to 3 cm, stage pTa-T1, signed informed consent to participate in the study and patients» readiness to undergo control examinations in inpatient setting for one year. The exclusion criteria were a confirmed or detected muscleinvasive tumor, multiple bladder involvement (> 3 tumors, as well as detected tumors spreading to the ureter, bladder neck, and prostatic urethra. The primary study endpoint was considered to be a recurrence of a tumor after TUR of the bladder (TURB. The secondary endpoint was the frequency of concealed bladder perforation, blood transfusions, recystoscopies for bladder tamponade, early recystoscopies to specify a BC stage, and the frequency of immediate intravesical injection of a chemical. For final analysis, the investigators selected 106 patients in a group where tumors were removed en bloc (a study group and 133 patients in a group where tumors were retrieved using traditional TURB (a control group. In the study group, the tumor was removed en bloc by a monopolar J-shaped electrode (sand wedge electrode in 45 patients, by a hook-like electrode in 14, by a hybrid procedure (hydropreparation and monopolar electrosurgery by a water-jet hybrid knife in 10, and by

  7. Transurethral en bloc resection of bladder tumors

    Directory of Open Access Journals (Sweden)

    A. G. Martov

    2015-03-01

    Full Text Available Background. The high incidence of recurrent non-muscle-invasive bladder carcinoma (BC necessitates searches for new surgical methods. Objective: to comparatively evaluate the efficiency and safety of en block resection of bladder tumors versus transurethral resection (TUR. Subjects and methods. In January 2010 to June 2013, a total of 292 patients with primary and recurrent bladder tumor stages, cTa-T2, underwent transurethral endoscopic treatment (as TUR at the Unit of Minimally Invasive Urology, Moscow City Clinical Hospital Fifty-Seven. A major portion of these patients were included in the study of the efficiency and safety of en bloc TUR of bladder tumors. The criteria for study inclusion were primary or recurrent non-muscle-invasive bladder tumor measuring 1 to 3 cm, stage pTa-T1, signed informed consent to participate in the study and patients» readiness to undergo control examinations in inpatient setting for one year. The exclusion criteria were a confirmed or detected muscleinvasive tumor, multiple bladder involvement (> 3 tumors, as well as detected tumors spreading to the ureter, bladder neck, and prostatic urethra. The primary study endpoint was considered to be a recurrence of a tumor after TUR of the bladder (TURB. The secondary endpoint was the frequency of concealed bladder perforation, blood transfusions, recystoscopies for bladder tamponade, early recystoscopies to specify a BC stage, and the frequency of immediate intravesical injection of a chemical. For final analysis, the investigators selected 106 patients in a group where tumors were removed en bloc (a study group and 133 patients in a group where tumors were retrieved using traditional TURB (a control group. In the study group, the tumor was removed en bloc by a monopolar J-shaped electrode (sand wedge electrode in 45 patients, by a hook-like electrode in 14, by a hybrid procedure (hydropreparation and monopolar electrosurgery by a water-jet hybrid knife in 10, and by

  8. Studies of experimental bladder tumors, 3

    International Nuclear Information System (INIS)

    Enzymatologic, histochemical and histologic investigations were performed on the effects of SLA, a β-glucoronidase inhibitor, and Linaic irradiation in an experimental BBN bladder tumor of rats. Bladder tumors were macroscopically thumb-head size in the cases with no treatment of with SLA application, but were shrunk by roentgen irradiation. The number of the rats with reduced tumor was respectively 3 in the group with roentgen irradiation. S-LDH activity of the cancer-carrying animals was markedly elevated as compared with that of the normal rat. SLA application caused no change in S-LDH activity of cancer-carrying animals, but roentgen irradiation resulted in a marked decrease in S-LDH activity of the similar animals with bladder tumors. The level of this decrease was dependent on the dosage of one time irradiation; no change was observed by 200, 300 and 500 rad, little decrease was seen by 750 rad, and marked decrease was observed after 1,000 and 1,500 rad radiation. Histological observation of the effects of irradiation could be summarized as follows. Histological changes were seen in the cases of macroscopic shrinkage by 3,000 rad irradiation. In this group, an individual variation was noticed not only macroscopically but microscopically. One time irradiation of 200, 300 and 500 rad resulted in no histological change, but that of 750, 1,000, and 1,500 rad caused a slight, but not marked, histological change. Tissue distribution of β-glucuronidase was examined by means of Naphthol-AS-BI-glucuronide method in the group without any treatment and the group with SLA administration. β-glucuronidase activity was noticed in the epithelial cells and interstitial stroma of the tumor tissue, but the effect of SLA on β-glucuronidase activity was not observed histochemically. (author)

  9. Computerized tomography and staging of bladder tumors

    International Nuclear Information System (INIS)

    Computed Tomography (CT) has been employed in 13 patients with bladder tumors; 8 of them subsequently underwent surgery. Concordance between CT and pathological staging ranged in 90% of accurate results. Our data are discussed and compared to those of other authors in the literature. Staging was carried out according to the International Union Against Cancer. CT proved to be very accurate in the assessment of local and regional spread of tumor, limphatic progression and early detection of ureteral obstruction, as well as diagnosis of distant metastasis in selected patients. In poor candidates for surgery CT provided invaluable data to be used for localizing fields of radiation therapy. CT is a very well tolerated procedure, it is therefore suitable in subsequent treatment control. (Author)

  10. TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW-DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA.

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    Choy, Kevin; Fidel, Janean

    2016-05-01

    Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross-sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once-daily fractions (Monday-Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first-line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction. PMID:26841125

  11. Superficial urinary bladder tumors treatment results: A 10-year experience

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    Stanković Jablan; Dinić Ljubomir; Pavlović Svetlana

    2007-01-01

    Background/Aim. The most common urinary bladder tumors are superficial tumors. Due to their tension to relapse and progress towards deeper layers after surgical therapy, an adequate therapy significantly contributed to the improvement of the results of urinary bladder tumors treatment. Staging and gradus of the tumor, presence of the carcinoma in situ (CIS) or relapses significantly influenced the choice of the therapy. The aim of this study was to ascertain the effectiveness of the intravesi...

  12. RARE CASE OF DESMOID TUMOR OF URINARY BLADDER

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    Chalapathy

    2015-08-01

    Full Text Available Desmoid tumor is a benign soft tissue tumor which belongs to a family of myofibroblastic fibromatoses. Occasionally, desmoid tumors have an unusual site of occurrence . We describe a case of incisional hernia in postmenopausal women with an intra operative incidental finding of a desmoid tumor from anterior wall of urinary bladder for which a wide excision was performed

  13. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    International Nuclear Information System (INIS)

    Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

  14. Tumor motion and deformation during external radiotherapy of bladder cancer

    International Nuclear Information System (INIS)

    Purpose: First, to quantify bladder-tumor motion in 3 dimensions during a 4-week to 5-week course of external radiotherapy. Second, to relate the motion to the tumor location on the bladder wall. Third, to extensively evaluate gross tumor volume (GTV) shape and volume changes during the course of the treatment. Methods and Materials: Multiple repeat computed tomography (CT) images were obtained for 21 bladder cancer patients. These scans were matched to the rigid bony anatomy. For each patient, the main direction and magnitude of the tumor movement was determined by use of principle-component analysis. To study GTV shape changes, all GTVs were registered to the GTV in the planning CT scan, and the residual shape errors were determined by measurement of edge variations perpendicular to the median surface. Results: Gross tumor volume translations were largest in cranial-caudal and anterior-posterior direction (SD, 0.1 to ∼0.9 cm). The translations were strongly correlated with the tumor location on the bladder wall. The average value of the local standard deviations of the GTV shape ranged from 0.1 to approximately 0.35 cm. Conclusions: Despite large differences in bladder filling, variations in GTV shape were small compared with variations in GTV position. Geometric uncertainties in the GTV position depended strongly on the tumor location on the bladder wall

  15. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

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    Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  16. Superficial urinary bladder tumors treatment results: A 10-year experience

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    Stanković Jablan

    2007-01-01

    Full Text Available Background/Aim. The most common urinary bladder tumors are superficial tumors. Due to their tension to relapse and progress towards deeper layers after surgical therapy, an adequate therapy significantly contributed to the improvement of the results of urinary bladder tumors treatment. Staging and gradus of the tumor, presence of the carcinoma in situ (CIS or relapses significantly influenced the choice of the therapy. The aim of this study was to ascertain the effectiveness of the intravesicelly applied BCG (Bacille Colmette - Guerin vaccine or chemiotherapy in the prevention of the relapses and further progression of superficial urinary bladder tumors. Methods. All of the diagnosed superficial tumors of bladder were removed by transurethral resection (TUR. After receiving the patohistological finding they were subjected to adjuvant therapy, immune BCG vaccine or chemiotherapy (epirubicin, doxorubicin, mitomycin-C. The third group did not accept adjuvant therapy, but had regularly scheduled cystoscopic controls. The appearance of relapses, progression of stage and grades of the tumor, as well as possible unwanted effects of adjuvant therapy were registered. Results. The applied immunotherapy (BCG influenced decreased tumor relapses (7% and statistically important difference between patients who had taken adjuvant chemotherapy (relapses 18.4% and those without this therapy was acknowledged. Grades of tumor did not show statistically significant difference on tumor relapse. A significantly longer period of time in the appearance of tumor relapse after BCG (29.33 months, had significant importance comparing to chemio (9.44 months or non-taken adjuvant therapy (9.84 months. Very small number of unwanted effects suggested an obligatory undertaking adjuvant therapy after TUR of superficial tumors. Conclusion. A significant decrease of relapses as well as avoidance of further progression of urinary bladder tumors, has introduced adjuvant therapy in

  17. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

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    Lamm, D.L.; Riggs, D.R.; DeHaven, J.I.; Bryner, R.W. (West Virginia Univ. School of Medicine, Morgantown (USA))

    1991-01-01

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone.

  18. Immunotherapy of murine bladder cancer by irradiated tumor vaccine

    International Nuclear Information System (INIS)

    This investigation explored the efficacy of irradiated autologous mouse bladder tumor (Ir-MBT2) as an active specific immunotherapeutic agent and as adjuvant therapy with Bacillus Calmette-Guerin (BCG) against a subcutaneously transplanted murine bladder tumor. Tumor incidence was significantly reduced in groups receiving BCG (27%, p less than 0.005) or Ir-MBT2 with BCG (53%, p less than 0.025), compared to control (93%). Survival was significantly improved in groups treated with BCG (100%, p less than 0.005), 10(5) Ir-MBT2 with BCG (53%, p less than 0.01), or 10(7) Ir-MBT2 with BCG (47%, p less than 0.025) compared with control (13%). Surprisingly, Ir-MBT2 consistently reduced the efficacy of BCG alone. Ir-MBT2 alone (10(7)) appeared to enhance tumor growth. Autologous irradiated bladder tumor vaccine, alone or in combination with BCG, displayed no immunotherapeutic advantage. The use of irradiated tumor cell vaccine for bladder cancer therapy may reduce the results achievable with BCG alone

  19. Diagnosing and Treating Inflammatory Myofibroblastic Tumor of the Bladder

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    Ridwan Alam

    2016-01-01

    Full Text Available Inflammatory myofibroblastic tumor (IMT is an uncommon condition that is rarely encountered in the urinary tract. In this report, we present a case of IMT of the bladder in a woman with multiple previous pelvic surgeries. We further review the relevant literature to highlight this rare but important clinical presentation.

  20. Recurrent and multiple bladder tumors show conserved expression profiles

    International Nuclear Information System (INIS)

    Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors

  1. Recurrent and multiple bladder tumors show conserved expression profiles

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    Knuutila Sakari

    2008-06-01

    Full Text Available Abstract Background Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors. Methods Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses. Results We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles. Conclusion Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.

  2. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model.

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    Scheepbouwer, Chantal; Meyer, Sandra; Burggraaf, Maroeska J; Jose, Jithin; Molthoff, Carla F M

    2016-01-01

    Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics. PMID:27533303

  3. A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model

    Science.gov (United States)

    Meyer, Sandra; Burggraaf, Maroeska J.; Jose, Jithin; Molthoff, Carla F. M.

    2016-01-01

    Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics. PMID:27533303

  4. Villous Tumor of the Urinary Bladder Resembling Low-grade Mucinous Neoplasm of the Appendix.

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    Ito, Ayako; Sakura, Yuma; Sugimoto, Mikio; Kakehi, Yoshiyuki; Kuroda, Naoto

    2016-05-01

    Mucinous neoplasms of the urinary tract are very rare. We present a 63-year-old-women who had a sessile papillary villous tumor in urinary bladder. Although transurethral resection of the bladder tumor (TURBT) was performed, the villous tumor repetitively recurred and gradually spread to the entire surface of bladder lumen. Histopathologic and immunohistochemical examination showed that the lesion was very similar to low-grade mucinous neoplasm arising in appendix vermiformis. There are no reports on appendiceal metaplasia of urinary bladder mucosa. In this case, we describe this unprecedented neoplasm as "villous tumor of the urinary bladder resembling low-grade mucinous neoplasm of the appendix." PMID:27169015

  5. Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder: case report

    International Nuclear Information System (INIS)

    The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor) of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms

  6. Holmium laser versus conventional transurethral resection of the bladder tumor

    Institute of Scientific and Technical Information of China (English)

    TENG Jing-fei; WANG Kai; YIN Le; QU Fa-jun; ZHANG Dong-xu; CUI Xin-gang; XU Dan-feng

    2013-01-01

    Background Transurethral resection of the bladder tumor (TURBT) remains the gold standard for non-muscle-invasive bladder cancer (NMIBC).Laser techniques have been widely used in urology.This analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor (HoLRBT) vs.TURBT.Methods A systemic search of MEDLINE,Embase,Web of Science,and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies.The pooled estimates of operation time,obturator nerve reflex rate,bladder perforation rate,bladder irrigation rate,catheterization time,hospital stay,and one-and two-year recurrence free survivals were calculated.Results Five studies were enrolled into our meta-analysis.No significant difference was observed in the operation time between groups (weighted mean difference (WMD) 1.01,95% confidential interval (95% CI)-3.52-5.54,P=0.66).The significant difference in the obturator nerve reflex (OR 0.05,95% CI 0.01-0.04,P=0.004),bladder perforation (OR 0.14,95% CI 0.03-0.61,P=0.009),bladder irrigation (OR 0.13,95% CI 0.04-0.45,P=0.001),catheterization time (WMD -0.96,95% CI-1.11 to-0.82,P <0.00001),and hospital stay (WMD-1.46,95% C1-1.65 to-1.27,P <0.00001) showed advantages of HoLRBT over TURBT.The 2-year recurrence free survival rate favors the HoLRBT group (OR 1.46,95%CI 1.02-2.11,P=0.04).Conclusions As a promising technique,HoLRBT is safe and efficient,and showed several advantages over TURBT.HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or Iow-orade early TNM-staoe urothelial carcinoma.

  7. Predictive factors for residual tumor and tumor upstaging on relook transurethral resection of bladder tumor in non-muscle invasive bladder cancer

    OpenAIRE

    Gill, Tejpal S.; Das, Ranjit K.; Supriya Basu; Dey, Ranjan K.; Subrata Mitra

    2014-01-01

    Context: Relook transurethral resection of bladder tumor (TURBT) improves the diagnostic and therapeutic efficacy of primary TURBT. However, it is still not established as to which category of patients would benefit most from this repeat invasive procedure. Aims: This prospective interventional study was designed to identify the category of patients with non-muscle invasive bladder cancer who may benefit from a routine relook procedure. Setting and Design: A total of 52 consecutive pa...

  8. Inflammatory myofibroblastic tumor of the bladder in a child: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Araujo Filho, Jose de Arimateia Batista, E-mail: ariaraujocg@hotmail.com [Radiology and Imaging Diagnosis, Instituto do Coracao (InCor) - Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil); Martines, Joao Augusto dos Santos; Martines, Brenda Margatho Ramos [Imaging Unit of Hospital Universitario - Universidade de Sao Paulo (HU-USP), Sao Paulo, SP (Brazil); Cavalcanti, Marcella Santos [Pathology, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HC-FMUSP), Sao Paulo, SP (Brazil); Cerri, Giovanni Guido; Castro, Claudio Campi de [Department of Radiology, Faculdade de Medicina da Universidade de Sao Paulo (FMUSP), Sao Paulo, SP (Brazil)

    2012-07-15

    Inflammatory myofibroblastic tumors rarely affect the urinary tract or children, and frequently mimic malignancy on imaging studies. According to the recent literature, only 35 cases of such bladder tumors in children have been reported. The authors present the case of a child with a bladder myofibroblastic tumor with favorable progression following complete surgical resection. (author)

  9. Microsatellite instability as prognostic marker in bladder tumors: a clinical significance

    OpenAIRE

    Mittal RD; Mandhani Anil; Vaish Minal; Mittal Balraj

    2005-01-01

    Abstract Background Carcinoma of urinary bladder is one of the leading causes of death in India. Successful treatment of bladder cancer depends on the early detection & specific diagnostic approaches. In the present study, microsatellite instability (MSI) has been evaluated as a prognostic marker in patients with superficial urinary bladder cancer in lower urinary tract for determining risk of recurrence. Methods A total of 44 patients with bladder tumors diagnosed with Transitional Cell Carc...

  10. Polycythemia vera revealed via a bladder tumor in a patient with erectile dysfunction: a case report

    OpenAIRE

    Bouchikhi, Ahmed-Amine; Tazi, Mohammed Fadl; Mellas, Soufiane; Amiroune, Driss; Elammari, Jalal Eddine; Khallouk, Abdelhak; El Fassi, Mohammed Jamal; Farih, Moulay Hassan

    2013-01-01

    Introduction Polycythemia vera is a polyglobular myeloproliferative syndrome related to the mutation of multipotent hemopoietic stem cells. This case report describes a patient whose bladder tumor was associated with polycythemia vera and erectile dysfunction. The association of bladder neoplasia with polycythemia vera and erectile dysfunction has not previously been reported in the literature. Case presentation A 40-year-old Moroccan man was followed up for a bladder tumor which manifested w...

  11. Clinical significance of transurethral tru-cut biopsy in confirmation of bladder tumor invasive character

    International Nuclear Information System (INIS)

    The objective of this study was to evaluate the feasibility of resection (TURBT) replacement in patients with strong suspicion of invasive bladder tumor by transurethral tru-cut biopsy carried out during cystoscopy. Fifty-eight patients (52 men and six women; mean age 65 years, range 43-79) presenting with extensive bladder tumor suggested by ultrasound and computed tomography were included in the study. Each patient was submitted to transurethral, cystoscopically-guided tru-cut biopsy of bladder tumor before the planned TURBT. Comparison of histopathological assessment of tissue cores, resection and radical cystectomy specimens was carried out. Histopathological analysis of resection specimens and tissue cores were in complete accordance with previous tissue cores assessment in terms of type and grade of bladder cancer. Histological type of bladder tumor revealed by tru-cut biopsy and radical cystectomy was identical in 56 (96.6%) cases. Tumor grade was the same in biopsy cores and radical cystectomy specimens in 55 (95%) cases. Endoscopic tru-cut bladder tumor biopsy allows us to collect sufficient amounts of tissue material for histopathological confirmation of detrusor muscle infiltration in patients presenting with bladder tumors suspected to cause muscle invasiveness. The procedure is carried out under cystoscopic control and is fast, efficient, safe, easy to perform and less invasive than standard TURB in cases of an extensive bladder tumor. (author)

  12. An Epigenomic Approach to Improving Response to Neoadjuvant Cisplatin Chemotherapy in Bladder Cancer.

    Science.gov (United States)

    Xylinas, Evanguelos; Hassler, Melanie R; Zhuang, Dazhong; Krzywinski, Martin; Erdem, Zeynep; Robinson, Brian D; Elemento, Olivier; Clozel, Thomas; Shariat, Shahrokh F

    2016-01-01

    Bladder cancer is among the five most common cancers diagnosed in the Western world and causes significant mortality and morbidity rates in affected patients. Therapeutic options to treat the disease in advanced muscle-invasive bladder cancer (MIBC) include cystectomy and chemotherapy. Neoadjuvant cisplatin-based combination chemotherapy is effective in MIBC; however, it has not been widely adopted by the community. One reason is that many patients do not respond to neoadjuvant chemotherapy, and no biomarker currently exists to identify these patients. It is also not clear whether a strategy to sensitize chemoresistant patients may exist. We sought to identify cisplatin-resistance patterns in preclinical models of bladder cancer, and test whether treatment with the epigenetic modifier decitabine is able to sensitize cisplatin-resistant bladder cancer cell lines. Using a screening approach in cisplatin-resistant bladder cancer cell lines, we identified dysregulated genes by RNA sequencing (RNAseq) and DNA methylation assays. DNA methylation analysis of tumors from 18 patients receiving cisplatin-based chemotherapy was used to confirm in vitro results. Cisplatin-resistant bladder cancer cells were treated with decitabine to investigate epigenetic sensitization of resistant cell lines. Our results show that HOXA9 promoter methylation status is associated with response to cisplatin-based chemotherapy in bladder cancer cell lines and in metastatic bladder cancer. Bladder cancer cells resistant to cisplatin chemotherapy can be sensitized to cisplatin by the DNA methylation inhibitor decitabine. Our data suggest that HOXA9 promoter methylation could serve as potential predictive biomarker and decitabine might sensitize resistant tumors in patients receiving cisplatin-based chemotherapy. PMID:27598218

  13. Detection of hyaluronic acid and laminin in serum of patients with urinary bladder tumors

    International Nuclear Information System (INIS)

    Objective: To investigate the serum Hyaluronic Acid (HA) and laminin (LN) level and its clinical significance in bladder tumors. Methods: Serum samples from 34 patients with bladder tumor and 30 cases as control group were analyzed by radioimmunoassay. Results: The results showed that the HA and LN levels of serum in patients with bladder tumors were significantly higher than that in control group (P<0.01) before operation, and decreased significantly after operation. The serum levels of HA and LN in infiltrated tumors were higher than that in superficial tumors (P<0.05). The markers in patients with lymph node metastasis were higher than that without lymph node metastasis (P<0.01). Conclusion: HA and LN take part in the malignant biology behavior of bladder tumors. They may be the important markers in assisting diagnosis and disease monitoring

  14. Intraoperative radiation therapy in patients with bladder cancer. A review of techniques allowing improved tumor doses and providing high cure rates without loss of bladder function

    International Nuclear Information System (INIS)

    Conventional external beam irradiation, using modern megavoltage techniques and doses that do not harm bladder function, will permanently eradicate local bladder cancer in 30% to 50% of patients, compared with 70% to 90% with cystectomy. In appropriately chosen patients, open surgery can safely provide excellent exposure for the selective delivery of more radiant energy directly to the tumor and less to the uninvolved portion of the bladder. Intraoperative radiation therapy, by either a removable radium or iridium implant or a large single dose of electrons, has been reported to be safe and can permanently cure the bladder of cancer and also preserve bladder function in more than 75% of patients with solitary tumors that invade into but not beyond the bladder muscle. With the increasing interest in and availability of intraoperative radiation therapy in the US, this curative and bladder-sparing treatment for operable patients with bladder cancer invading the trigone is appropriate for careful clinical trial. 13 references

  15. Factors related to recurrence of bladder transitional cell carcinoma after transurethral resection of bladder tumor (TUR-BT)

    International Nuclear Information System (INIS)

    The purpose of this study is to evaluate factors related to the recurrence of TCC (transitional cell carcinoma) in the urinary bladder after transurethal resection of bladder tumor (TUR-BT). We retrospectively reviewed 54 patients in whom TCC (transitional cell carcinoma) after TUR-BT had been confirmed. Recurrence was evaluated by US, CT, cystoscopy and urine smear during the follow-up period of 6 months. The multiplicity, shape, size, and calcification of TCC, as revealed by radiologic studies, were evaluated retrospectively before TUR-BT. After TUR-BT, the histologic grade and pathologic stage of TCC were evaluated. Radiologically, multiple and/or sessile type TCC had a higher recurrence rate than the single and/or pedunculated type. Pathologically, when the grade and stage of bladder tumor were higher, recurrent rates were higher. (author). 17 refs., 3 tabs., 3 figs

  16. A Large Bladder Tumor Covered With a Thick “Shell” of Necrotic Material

    Science.gov (United States)

    Wang, Lei; Zhou, Zhe; Gong, Miao-zi; Pan, Dong-liang; Zhang, Xiang-hua; Li, Ning-chen; Na, Yan-qun

    2016-01-01

    Abstract Bladder tumor arising in a spina bifida patient is rare and may be clinically latent. We report the case of a 61-year-old female patient with spina bifida, neurogenic bladder, and a history of recurrent urinary tract infections. A B-ultrasound and non-contrast computed tomography scan did not reveal any bladder mass, but an unexplained “well-filled” bladder was observed, which was confusing as the catheter was present and open. However, a subsequent cystoscopic evaluation revealed a large bladder mass measuring 9.5 × 9.0 × 6.5 cm3, which almost filled the entire bladder. The mass had coarse and flocculent surface and seemed to be free from each observed wall of the urinary bladder. It was diagnosed as an infectious necrotic mass based on its appearance. During transurethral resection of the mass, a bladder tumor was suspected as small blood vessels and bleeding appeared within the inner layer of the mass. Pathological examination revealed necrotic material, inflammatory cells, and urothelial carcinoma cells. Then, a radical cystectomy was performed, and the pathological results indicated stage pT3bN0M0 transitional cell carcinoma. In the gross specimen, the base of the tumor measured 3 × 3 cm2 on the top of the back wall of the bladder. Bladder tumors may have atypical presentations in patients with spina bifida. Regular screening is helpful for earlier detection and improving outcomes of bladder tumors in such patients. PMID:27100442

  17. Inflammatory pseudotumor of the urinary bladder: A case series among more than 2,000 urinary bladder tumor cases

    Directory of Open Access Journals (Sweden)

    Mohamed M Elawdy

    2016-01-01

    Full Text Available “Inflammatory pseudotumor” (IPT has infrequently been reported in the medical journals. A retrospective analysis was conducted among more than 2,000 bladder tumor cases from January 1999 to December 2012 looking for patients with IPT in the final diagnosis. Six patients were found with median tumor size of 3.5 cm (range: 3–8 cm; computed tomography and/or magnetic resonance imaging was used to diagnose the tumor. All patients had complete resection of the tumors. On a median follow-up of 6 years (range: 2–10 years, no recurrences for IPT have been observed in all patients. We concluded that IPT is a rare disease of the urinary bladder and should be regarded with a high degree of suspicion. Although an extensive workup may be needed for definite diagnosis, it is worth to avoid unnecessary chemoradiotherapy or radical surgeries.

  18. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    Science.gov (United States)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  19. A Large Bladder Tumor Covered With a Thick “Shell” of Necrotic Material

    OpenAIRE

    Wang, Lei; Zhou, Zhe; Gong, Miao-zi; Pan, Dong-liang; ZHANG, XIANG-HUA; Li, Ning-chen; Na, Yan-qun

    2016-01-01

    Abstract Bladder tumor arising in a spina bifida patient is rare and may be clinically latent. We report the case of a 61-year-old female patient with spina bifida, neurogenic bladder, and a history of recurrent urinary tract infections. A B-ultrasound and non-contrast computed tomography scan did not reveal any bladder mass, but an unexplained “well-filled” bladder was observed, which was confusing as the catheter was present and open. However, a subsequent cystoscopic evaluation revealed a ...

  20. Cystitis glandularis forming a tumorous lesion in the urinary bladder: A rare appearance of disease

    OpenAIRE

    Shigehara, Kazuyoshi; Miyagi, Tohru; Nakashima, Takao; Shimamura, Masayoshi

    2008-01-01

    We report a rare appearance of cystitis glandularis forming a tumorous lesion with blueberry spots in the urinary bladder. A 49-year-old woman was admitted to our hospital with pollakisuria and recurrent gross hematuria. Urine examination showed no pyuria. Computed tomography (CT) scan showed an extravesical invasive mass and cystoscopy revealed a non-papillary tumor with blueberry spots in the bladder. Transurethral resection (TUR) was performed. Histopathological examination revealed cystit...

  1. Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation

    International Nuclear Information System (INIS)

    Purpose: Several groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TUR-B) and radiochemotherapy (RCT). As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma. Methods and Materials: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT. Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables. Results: A high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0.001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years. Conclusion: Patients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT

  2. Relationship between thermometry results and tumor response in thermoradiotherapy

    International Nuclear Information System (INIS)

    Clinical results of thermoradiotherapy for various tumors at Kyoto University were reviewed with a special attention to the relationship between thermometry results and tumor response. Thermometry for superficial and subsurface tumors were satisfactory, and continuous multipoint thermometry could be performed for the tumors. Thermal parameters predicting complete tumor regression were minimum tumor temperature, minimum equivalent time at 43degC, and number of the treatment goal heat sessions. On the other hand, thermal data obtained were insufficient for deep-seated tumors, and no significant relationship could be demonstrated between tumor response and thermal parameters for deep-seated tumors. On the other hand, significant correlation between tumor degeneration and intravesical temperatures was demonstrated for bladder tumors. Until non-invasive thermometry is available clinically, temperature measurements of bladder or rectal cavity can be an alternative method of direct insertion of thermal probes into the pelvic tumors. Because a significant relationship between certain thermal parameters and tumor response was demonstrated for superficial tumors, stringent quality control of thermometry is required for the success of clinical hyperthermia of both superficial and deep-seated tumors. (author)

  3. Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

    International Nuclear Information System (INIS)

    In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

  4. Trace metals and over-expression of metallothioneins in bladder tumoral lesions: a case-control study

    Directory of Open Access Journals (Sweden)

    Cymbron Teresa

    2009-07-01

    Full Text Available Abstract Background Previous studies have provided some evidence of a possible association between cancer and metallothioneins. Whether this relates to an exposure to carcinogenic metals remains unclear. Methods In order to examine the association between the expression of metallothioneins and bladder tumors, and to compare the levels of arsenic, cadmium, chromium, lead and nickel in animals with bladder tumors and animals without bladder tumors, 37 cases of bovine bladder tumors and 17 controls were collected. The detection and quantification of metallothioneins in bladder tissue of both cases and controls was performed by immunohistochemistry. And the quantification of metals in tissue and hair was assessed by inductively coupled plasma – mass spectrometry. Results Increased expression of metallothioneins was associated with bladder tumors when compared with non-tumoral bladder tissue (OR = 9.3, 95% CI: 1.0 – 480. The concentrations of cadmium, chromium, lead and nickel in hair of cases were significantly higher than those of controls. However, as for the concentration of metals in bladder tissue, the differences were not significant. Conclusion Though the sample size was small, the present study shows an association between bladder tumors and metallothioneins. Moreover, it shows that concentrations of metals such as cadmium, chromium, lead and nickel in hair may be used as a biomarker of exposure.

  5. Lewis antigen mediated adhesion of freshly removed human bladder tumors to E-selectin

    DEFF Research Database (Denmark)

    Skorsteensgaard, Karna; Vestergaard, Else Marie; Langkilde, Niels; Christensen, Lise Lotte; Wolf, Hans; Ørntoft, Torben Falck

    1999-01-01

    PURPOSE: Twenty fresh surgical specimens of human bladder tumors were tested for their ability to adhere to recombinant P and E-selectin. The adhesion was correlated to immunological detection of carbohydrate structures. MATERIALS AND METHODS: A static titertray assay with immobilized selectins and...... appropriate controls was used for bladder tumor cell adhesion. On the same tumors expression of carbohydrate structures was examined by immunohistochemistry and Western blotting. RESULTS: No tumor bound to P-selectin. Nine tumors showed a high number of cells binding to E-selectin, 5 showed intermediate...... binding, and 6 showed only rare binding. The specificity of the binding was verified by inhibition with EDTA, by blocking antibodies to E-selectin, and by an acrylamide based sLe(x) (Galbeta1-4 [Fucalpha1-3]GlcNAc-) polymer. The binding was significantly more frequent (p <0.045) in superficial tumors than...

  6. The Potential Value of EGFR and P53 Immunostaining in Tumors of the Urinary Bladder

    Directory of Open Access Journals (Sweden)

    Ibrahim N

    2009-01-01

    Full Text Available The expression of EGFR and p53 has not been adequately studied as a prognostic tool in urinary bladder tumors. We analyzed 74 bladder cancer samples from Egypt for EGFR and p53 expression using immunohistochemistry. The tumors were of different histological types, grades and clinical stages, and with established lymph node status. Almost 61% of the tumors showed positive membranous EGFR expression and 74.3% had positive nuclear staining of p53. Analysis of correlation of the IHC staining with clinical variables showed a significant correlation only between EGFR expression and histological type (p=0.002, ANOVA, in that the expression was higher in squamous cell carcinomas than in other histological types. There were no significant correlations between p53 or EGFR with the other clinicopathological variables, including age, sex, staging, grading, and lymph node status. Further studies are needed to determine if EGFR and p53 might be used as prognostic tools in bladder cancer.

  7. Urinary bladder tumors among atomic bomb survivors Hiroshima and Nagasaki, 1961-1972

    International Nuclear Information System (INIS)

    A study was made of the relationship of radiation dose to the incidence of urinary bladder tumors among atomic bomb survivors and controls in the RERF Life Span Study extended sample. A total of 112 cases of urinary bladder tumors was identified among approximately 99,000 subjects in this fixed cohort during 1961-72. Morphologic diagnoses were available for 86 cases (76.8%), cystoscopy alone for 21 cases (18.7%), and only the cause of death recorded on death certificates for 5 cases (4.5%). Urothelial carcinoma (transitional cell carcinoma) is the most common type of urinary bladder tumor for which morphologic diagnoses are available. The 1961-72 incidence rate was calculated using 106 cases identified as urinary bladder tumors. Although the crude annual incidence rate in the high dose group (100 rad or more) is elevated in both cities and both sexes, all nine cases with this dose were aged 40 years or more at the time of the bomb (ATB). The standardized relative risk adjusted for city and sex for those of age 40 or more ATB in the high dose group is 1.8 in comparison with the control group and this is a suggestive statistical difference. A statistically significant elevation of risk occurs in the high dose group for urothelial carcinoma and adenocarcinoma of the urinary bladder among those aged 40 or more ATB. (author)

  8. A New Method of Establishing Orthotopic Bladder Transplantable Tumor in Mice

    International Nuclear Information System (INIS)

    The present study aims to find a convenient, rapid, and stable method to establish bladder tumor in mice. Female Balb/C-nu-nu nude mice (or female T739 mice) were narcotized by sodium pentobarbital at a dosage of 60 mg/kg. The stylet of the 24# venous retention needles was bent in a 5° to 7° angle at a distance of 15 mm from the needlepoint to form a circle with 2.61 mm to 3.66 mm radius when the stylet is rotated. The pipe casing was lubricated with liquid paraffin, and inserted into the bladder cavity. The drift angle stylet was inserted into the pipe casing slowly, rotated for five times, and then pulled out. A cell suspension (0.1 mL) of approximately 1×106 T24 cells (or BTT cells) was then injected immediately. A total of 60 T739 mice and 60 Balb/C-nu-nu nude mice were inoculated with BTT cells and T24 cells, respectively. The bladder tumor incidence and the average survival time of the tumor-bearing mice were 100% and (26.69±9.24) d and 100% and (34.59±9.8) d for the T739 mice and Balb/C-nu-nu nude mice, respectively. Using the drift angle stylet to injure the mucous membrane of the urinary bladder can establish a stable bladder transplantable tumor model in mice

  9. Detection of Serum Hyaluronic Acid and Laminin in Patients with Bladder Tumors

    Institute of Scientific and Technical Information of China (English)

    李令勋; 丁国富

    2003-01-01

    In order to investigate the changes of serum hyaluronic acid (HA) and laminin (LN) levels and their clinical implication in the patients with bladder tumors, the serum HA and LN levels in 34 patients with bladder tumor and 30 cases of control group were detected by radioimmunoassay before and after operation. The results showed that the serum HA and LN levels in the patients with bladder tumors were significantly higher than those in control group (P<0. 01) before operation, and decreased significantly after operation (P<0. 05). The serum levels of HA and LN in infiltration tumors were higher than those in superficial tumors (P<0.05). The serum HA and LN levels in patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.01 ). The investigation revealed that HA and LN might be involved in the malignant biology behavior of bladder tumors and could be used as important markers of assistant diagnosis and condition monitoring.

  10. Updating computed tomography of bladder carcinoma in assessing response to immunotherapy and attenuated irradiation

    International Nuclear Information System (INIS)

    Computed tomography was utilized as part of the surgical-pathological-radiological evaluation of 21 patients who were treated for bladder carcinoma with attenuated irradiation and immunotherapy. Fifteen patients had moderately infiltrative (Stage Tsub(2a-b) or less) disease and it was found that a routine high resolution CT technique using a modern fast scanner delineated the tumor in most cases. More accurate assessment of tumor response to therapy and evaluation of tumor progression was facilitated using a gas insufflation technique combined with intravenous contrast infusion. This was followed in selected cases by quantitative measurements of CT attenuation values using a recently introduced CT software program. Using this program, individual pixel values were obtained in selected areas and evaluation of the resulting numerical data and pixel histograms aided in the differentiation of tumor tissue from adjacent bladder wall and mapped out areas of tumor necrosis. Our preliminary observations suggest that quantitative CT studies incorporating assessment of printouts of attenuation values of adjacent pixels within a region of interest will improve the delineation of smaller (Tsub(2a)/Tsub(2b)) lesions and will aid objective characterization of tumor tissue during and following therapy. (orig.)

  11. Bladder Tumor in Women with Microscopic Hematuria: An Iranian Experience and a Review of the Literature

    Science.gov (United States)

    Abbaszadeh, Shahin; Taheri, Saeed; Nourbala, Mohammad Hossein

    2009-01-01

    Aim. In this study we report our experience with microhematuria and its relation with bladder tumors in Iranian women. Materials and Methods. Overall 249 women were evaluated. Microscopic hematuria was defined as three or more red blood cells per high-power field on at least two different occasions. Patients with a history of gross hematuria or coagulation disorders, having organic diseases, urinary stones, urinary tract infections, nephrological diseases, and local lesions such as urethral caruncle were excluded from the study population. Final diagnosis of malignant tumors was done with cystoscopy and biopsy specimen pathological assessment in all cases. Results. Age for the study population was 49.7 ± 11.8 years. 95 (38%) of patients were identified during routine check up and presenting symptoms in other patients were frequency, dysuria, stress urge incontinence, urge incontinence, feeling of incomplete urine emptying, and flunk pain, respectively. Finally, 7 (2.8%) of study subjects were confirmed as having bladder tumors. One of tumor cases was diagnosed 24 months after initial assessments. Patients with bladder tumor were significantly older; more frequently had diverticulum in their bladder wall (P < .05). Conclusion. Female microscopic hematuria is relevant and deserves evaluations, especially in elderly patients. Patients whose reason for microhematuria would not be diagnosed at the initial evaluations should be followed. PMID:19639044

  12. Photodynamic therapy: development of a treatment and dosimetry system adapted to superficial tumors of the bladder

    Science.gov (United States)

    Lignon, Dominique; Jaboin, Y.; Wolf, D.; Meunier-Reynes, Anne; Guillemin, Francois H.

    1993-06-01

    Superficial tumors of the bladder or in situ carcinoma could be interesting indications of Photodynamic Therapy (PDT), since a total mutilating cystectomy could be avoided. The plurifocality of the lesions requires a treatment of the whole mucose; the quantity of light energy must be homogenous and sufficient to induce a therapeutic effect, still non toxic for normal tissues. We therefore developed a system of treatment and intravesical dosimetry control so that the operator can have precise information on the light repartition in the bladder in real time to enable him to optimize the positioning of the irradiation source. This intravesical device consists of twelve light sensors with optical fiber distributed symmetrically against the walls of the bladder; the emitting source is constituted of a scattering isotropic sphere. The signals emitted by the sensors are converted into tension. The acquisition part of the system values consists of two parts : an analogic part, the values are multiplexed on a same oscilloscope track to see in real time their evolution according to the position of the emitting source. The other part is constituted by the numeric acquisition of values for further analysis. We developed, from a mathematical modelisation of the bladder, a centering program of the diffusor that indicates its position in the bladder, as well as a cartography program where the bladder is re-built by interpolation with the different lighting levels.

  13. DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

    International Nuclear Information System (INIS)

    Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence. A set of 4 genes, including CDH1 (E-cadherin), SFN (stratifin), RARB (retinoic acid receptor, beta) and RASSF1A (Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters. CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group. Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a

  14. A new non-muscle-invasive bladder tumor-homing peptide identified by phage display in vivo

    Science.gov (United States)

    YANG, XIAOFENG; ZHANG, FAN; LUO, JUNQIAN; PANG, JIANZHI; YAN, SANHUA; LUO, FANG; LIU, JIEHAO; WANG, WEI; CUI, YONGPING; SU, XIXI

    2016-01-01

    Bladder cancer is common and widespread, and its incidence is increasing. Many new diagnostic methods combined with state-of-the-art technology have been introduced in cystoscopy to collect real-time images of the bladder mucosa for diagnosis, but often miss inconspicuous early-stage tumors. Fluorophore-labeled peptides with high sensitivity and specificity for cancer would be a desirable tool for the detection and treatment of tiny or residual bladder tumors. Phage display and the human non-muscle-invasive bladder cancer cell line BIU-87 were used to identify a peptide. The isolated phage display peptide (CSSPIGRHC, named NYZL1) was tested in vitro for its binding specificity and affinity. Accumulation into xenograft tumors in a nude mouse model was analyzed with FITC-labeled NYZL1. NYZL1, with strong tumor-homing ability, was identified by in vivo phage library selection in the bladder cancer model. The NYZL1 phage and synthetic FITC-labeled NYZL1 peptides bound to tumor tissues and cells, but were hardly detected in normal control organs. Notably, accumulation of FITC-NYZL1 in bladder tumor cells was time-dependent. Biodistribution studies of xenografts of BIU-87 cells showed accumulation of injected FITC-NYZL1 in the tumors, and the bound peptide could not be removed by perfusion after 24 h. The mouse model of bladder tumor showed increased fluorescence intensity in the tumor-bearing bladder in comparison with normal bladder tissues after 4–6 h. In conclusion, NYZL1 may represent a lead peptide structure applicable in the development of optical molecular imaging. PMID:27221614

  15. Targeting bladder tumor cells in voided urine of Chinese patients with FITC-CSNRDARRC peptide ligand

    Directory of Open Access Journals (Sweden)

    Jia XY

    2012-05-01

    Full Text Available Xing-You Jia1, Qi Yu2, Zhe-Hui Zhang3, Xiao-Feng Yang11School of the First Clinical Hospital, Shanxi Medical University, Taiyuan, Shanxi, China; 2Department of Information Management, Shanxi Medical University, Taiyuan, Shanxi, China; 3Research Center for Philosophy of Science and Technology, Shanxi University, Taiyuan, Shanxi, ChinaObjective: To study the practicality of the FITC-CSNRDARRC peptide ligand (containing the Cys–Ser–Asn–Arg–Asp–Ala–Arg–Arg–Cys nonapeptide in diagnosing and monitoring bladder tumors.Materials and methods: Between March 2011 and September 2011, 80 consecutive patients with radiographic abnormalities, localizing hematuria, other symptoms, or signs were studied using the FITC-CSNRDARRC ligand, urinary cytology (UC, and fluorescence in situ hybridization (FISH. The sensitivity and specificity of these three technologies were determined and compared. Cystoscopy and tissue biopsy were taken as the “gold standards” for bladder tumor diagnosis in this study.Results: Twenty-nine out of 80 patients were diagnosed with a bladder tumor via histopathological examination. The FITC-CSNRDARRC ligand was positive in 23 out of 29 bladder tumor patients and produced false negatives in six (20.69% patients. The UC was positive in six out of 29 bladder tumor patients and produced false negatives in 23 (79.31% patients. The FISH was positive in 21 out of 29 bladder tumor patients and produced false negatives in eight (27.59% patients. The overall sensitivity as verified by the FITC-CSNRDARRC ligand was much higher than in UC (79.31% versus 20.69%, P < 0.001 and was slightly higher than in FISH (79.31% versus 72.41%, P = 0.625. The sensitivity of FISH was significantly higher than that of UC (72.41% versus 20.69%, P < 0.001. Sensitivities of the FITC-CSNRDARRC ligand and UC by grade were 58.33% versus 8.3% for low-grade (LG tumors (P = 0.031 and 94.12% versus 29.41% for high-grade (HG tumors (P = 0.003, respectively

  16. A Large Bladder Tumor Covered With a Thick "Shell" of Necrotic Material: Misdiagnosis of a Patient With Spina Bifida.

    Science.gov (United States)

    Wang, Lei; Zhou, Zhe; Gong, Miao-Zi; Pan, Dong-Liang; Zhang, Xiang-Hua; Li, Ning-Chen; Na, Yan-Qun

    2016-04-01

    Bladder tumor arising in a spina bifida patient is rare and may be clinically latent.We report the case of a 61-year-old female patient with spina bifida, neurogenic bladder, and a history of recurrent urinary tract infections. A B-ultrasound and non-contrast computed tomography scan did not reveal any bladder mass, but an unexplained "well-filled" bladder was observed, which was confusing as the catheter was present and open. However, a subsequent cystoscopic evaluation revealed a large bladder mass measuring 9.5 × 9.0 × 6.5 cm, which almost filled the entire bladder. The mass had coarse and flocculent surface and seemed to be free from each observed wall of the urinary bladder. It was diagnosed as an infectious necrotic mass based on its appearance.During transurethral resection of the mass, a bladder tumor was suspected as small blood vessels and bleeding appeared within the inner layer of the mass. Pathological examination revealed necrotic material, inflammatory cells, and urothelial carcinoma cells. Then, a radical cystectomy was performed, and the pathological results indicated stage pT3bN0M0 transitional cell carcinoma. In the gross specimen, the base of the tumor measured 3 × 3 cm on the top of the back wall of the bladder.Bladder tumors may have atypical presentations in patients with spina bifida. Regular screening is helpful for earlier detection and improving outcomes of bladder tumors in such patients. PMID:27100442

  17. Detection of bovine papillomavirus type 14 DNA sequences in urinary bladder tumors in cattle.

    Science.gov (United States)

    Roperto, Sante; Munday, John S; Corrado, Federica; Goria, Maria; Roperto, Franco

    2016-07-15

    Bovine papillomavirus type 14 (BPV-14) is a novel Deltapapillomavirus (δPV) which is most closely related to BPV-1, -2, and -13, well-known members of the δPV genus. So far BPV-14 has been detected in cutaneous neoplastic lesions in cattle and in feline sarcoids. As BPV-14 may share biological and pathological properties with BPV-1, -2 and -13, it has been hypothesized that, like other δPVs, BPV-14 could be associated with bovine bladder neoplasia. In this study, 50 tumors of the urinary bladder of cattle were diagnosed. DNA was extracted from all tumor samples as well as from 25 normal bladder samples and submitted to BPV-14 L1 PCR and subsequent amplicon sequencing analysis. BPV-14 L1 DNA sequences of specific 195bp amplicons were obtained from 17 of 50 (34%) tumor DNA isolates; no BPV-14 DNA was detected from 25 normal samples. Amplicons revealed a 99% homology with the corresponding BPV-14 L1 DNA region (GenBank accession number KP276343.1). Co-infections by two or three δPV types were also seen. This study reveals the presence of BPV-14 DNA alone or in combination with other δPV DNA in bovine bladder tumors alone and suggests that BPV-14 could also be involved in bladder neoplasia as its E5 oncoprotein has the potential to induce cell proliferation. Furthermore, this is the first study to show the presence of BPV-14 in Europe, suggesting that BPV-14, like other δPVs, has a worldwide distribution. PMID:27283849

  18. Androgenic dependence of exophytic tumor growth in a transgenic mouse model of bladder cancer: a role for thrombospondin-1

    Directory of Open Access Journals (Sweden)

    Yao Jorge L

    2008-04-01

    Full Text Available Abstract Background Steroid hormones influence mitogenic signaling pathways, apoptosis, and cell cycle checkpoints, and it has long been known that incidence of bladder cancer (BC in men is several times greater than in women, a difference that cannot be attributed to environmental or lifestyle factors alone. Castration reduces incidence of chemically-induced BC in rodents. It is unclear if this effect is due to hormonal influences on activation/deactivation of carcinogens or a direct effect on urothelial cell proliferation or other malignant processes. We examined the effect of castration on BC growth in UPII-SV40T transgenic mice, which express SV40 T antigen specifically in urothelium and reliably develop BC. Furthermore, because BC growth in UPII-SV40T mice is exophytic, we speculated BC growth was dependent on angiogenesis and angiogenesis was, in turn, androgen responsive. Methods Flat panel detector-based cone beam computed tomography (FPDCT was used to longitudinally measure exophytic BC growth in UPII-SV40T male mice sham-operated, castrated, or castrated and supplemented with dihydrotestosterone (DHT. Human normal bladder and BC biopsies and mouse bladder were examined quantitatively for thrombospondin-1 (TSP1 protein expression. Results Mice castrated at 24 weeks of age had decreased BC volumes at 32 weeks compared to intact mice (p = 0.0071 and castrated mice administered DHT (p = 0.0233; one-way ANOVA, JMP 6.0.3, SAS Institute, Inc.. Bladder cancer cell lines responded to DHT treatment with increased proliferation, regardless of androgen receptor expression levels. TSP1, an anti-angiogenic factor whose expression is inhibited by androgens, had decreased expression in bladders of UPII-SV40T mice compared to wild-type. Castration increased TSP1 levels in UPII-SV40T mice compared to intact mice. TSP1 protein expression was higher in 8 of 10 human bladder biopsies of normal versus malignant tissue from the same patients. Conclusion

  19. Tissue responses to hexyl 5-aminolevulinate-induced photodynamic treatment in syngeneic orthotopic rat bladder cancer model: possible pathways of action

    Science.gov (United States)

    Arum, Carl-Jørgen; Gederaas, Odrun A.; Larsen, Eivind L. P.; Randeberg, Lise L.; Hjelde, Astrid; Krokan, Hans E.; Svaasand, Lars O.; Chen, Duan; Zhao, Chun-Mei

    2011-02-01

    Orthotopic bladder cancer model in rats mimics human bladder cancer with respect to urothelial tumorigenesis and progression. Utilizing this model at pT1 (superficial stage), we analyze the tissue responses to hexyl 5-aminolevulinate-induced photodynamic therapy (HAL-PDT). In comparison to untreated rats, HAL-PDT causes little change in tumor-free rat bladder but induces inflammatory changes with increased lymphocytes and mononuclear cell infiltration in rat bladders with tumor. Immunohistochemistry reveals that HAL-PDT is without effect on proliferating cell nuclear antigen expression within the tumor and increases caspase-3 expression in both normal urothelium and the tumor. Transmission electron microscopy reveals severe mitochondrial damage, formations of apoptotic bodies, vacuoles, and lipofuscin bodies, but no microvillus-formed niches in HAL-PDT-treated bladder cancer rats. Bioinformatics analysis of the gene expression profile indicates an activation of T-cell receptor signaling pathway in bladder cancer rats without PDT. HAL-PDT increases the expression of CD3 and CD45RA in the tumor (determined by immunohistochemistry). We suggest that pathways of action of HAL-PDT may include, at least, activations of mitochondrial apoptosis and autophagy, breakdown of cancer stem cell niches, and importantly, enhancement of T-cell activation.

  20. The Vascular-Targeting Fusion Toxin VEGF121/rGel Inhibits the Growth of Orthotopic Human Bladder Carcinoma Tumors

    Directory of Open Access Journals (Sweden)

    Khalid Mohamedali

    2005-10-01

    Full Text Available Vascular endothelial growth factor. (VEGF and its receptors. (FLT-1 and KDR are overexpressed by human bladder cancer cells and tumor endothelial cells, respectively. Strategies that target VEGF receptors hold promise as antlanglogenic therapeutic approaches to bladder cancer. A fusion protein of VEGF121 and the plant toxin gelonin (rGel was constructed, expressed in bacteria, purified to homogeneity. Cytotoxicity experiments of VEGF121/rGel on the highly metastatic 253J B-V human bladder cancer cell line demonstrated that the VEGF121/rGel does not specifically target these cells, whereas Western blot analysis showed no defectable expression of KDR. Treatment with VEGF121/rGel against orthotopically implanted 253J B-V xenografts in nude mice resulted in a significant suppression of bladder tumor growth (-60% inhibition; P < .05 compared to controls. lmmunohistochemistry studies of orthotopic 253J B-V tumors demonstrated that KDR is highly overexpressed in tumor vasculature. Immunofluorescence staining with antibodies to CD-31 (blood vessel endothelium and reel demonstrated a dramatic colocalization of the construct on tumor neovasculature. Treated tumors also displayed an increase in terminal deoxynucleotidyl transferase-mediated dUTPblotin end labeling staining compared to controls. Thus, VEGF121/rGel inhibits the growth of human bladder cancer by cytotoxic effects directed against the tumor vascular supply and has significant potential as a novel antlangiogenic therapeutic against human bladder cancer.

  1. Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients

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    Mohamed Azza M

    2011-04-01

    Full Text Available Abstract Background/Objective Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones. Methods This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO, fructosamine, lactate dehydrogense (LDH, aspartate aminotransferase (AST, alanine aminotransferase (ALT, total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE and tumor necrosis factor alpha (TNF-α. In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK, lactate dehydrogenase (LDH, aspartate aminotransferase (AST and alanine aminotransferase (ALT. Results Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-α than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients. Conclusions It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer.

  2. Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne B; Dyrskjøt, Lars; von der Maase, Hans;

    2007-01-01

    and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry in...... strong independent prognostic factors for response and survival after cisplatin-containing chemotherapy in patients with advanced bladder cancer.......PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...

  3. Calpain3 is expressed in a proteolitically active form in papillomavirus-associated urothelial tumors of the urinary bladder in cattle.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available BACKGROUND: Calpain 3 (Capn3, also named p94, is a skeletal muscle tissue-specific protein known to be responsible for limb-girdle muscular dystrophy type 2A (LGMD2A. Recent experimental studies have hypothesized a pro-apoptotic role of Capn3 in some melanoma cell lines. So far the link between calpain3 and tumors comes from in vitro studies. The objective of this study was to describe Capn3 activation in naturally occurring urothelial tumors of the urinary bladder in cattle. METHODS AND FINDINGS: Here we describe, for the first time in veterinary and comparative oncology, the activation of Capn3 in twelve urothelial tumor cells of the urinary bladder of cattle. Capn3 protein was initially identified with nanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC-MS/MS in a co-immunoprecipitation experiment on E2F3, known to be a transcription factor playing a crucial role in bladder carcinogenesis in humans. Capn3 expression was then confirmed by reverse transcription polymerase chain reaction (RT-PCR. Finally, the Ca(2+-dependent proteolytic activity of Capn3 was assayed following ion exchange chromatography. Morphologically, Capn3 expression was documented by immunohistochemical methods. In fact numerous tumor cells showed an intracytoplasmic immunoreactivity, which was more rarely evident also at nuclear level. In urothelial tumors, bovine papillomavirus type 2 (BPV-2 DNA was amplified by PCR and the expression of E5 protein, the major oncogenic protein of BVP-2, was detected by western blotting, immunohistochemistry, and immunofluorescence. E2F3 overexpression and pRb protein downregulation were shown by western blotting. CONCLUSION: The role of capn3 protein in urothelial cancer of the urinary bladder remains to be elucidated: further studies would be required to determine the precise function of this protease in tumor development and progression. However, we suggest that activated Capn3 may be involved in molecular

  4. Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn syndrome.

    Science.gov (United States)

    Marte, Antonio; Indolfi, Paolo; Ficociello, Carmine; Russo, Daniela; Oreste, Matilde; Bottigliero, Gaetano; Gualdiero, Giovanna; Barone, Ciro; Vigliar, Elena; Indolfi, Cristiana; Casale, Fiorina

    2013-01-01

    Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm described in several tissues and organs including genitourinary system, lung, head, and neck. The etiology of IMT is contentious, and whether it is a postinflammatory process or a true neoplasm remains controversial. To our knowledge, we report the first reported case of IMT of urinary bladder in a pediatric patient with Wolf-Hirschhorn (WHS). We also review the literature about patients with associated neoplasia. PMID:24024066

  5. Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors

    Institute of Scientific and Technical Information of China (English)

    Nan YANG; Sheng-hua LI; Yun-zhe L(U); Li-shan CHEN; Da-ming REN

    2011-01-01

    Aim: To examine whether attenuated Salmonella typhimurium (S typhimurium) could be used as an anti-cancer agent or a tumortargeting vehicle for delivering shRNA-expressing pDNA into cancer cells in a mouse tumor model.Methods: Mouse bladder transitional cancer cell line (BTT-T739) expressing GFP was used, in which the GFP expression level served as an indicator of RNA interference (RNAi). BTT-T739-GFP tumor-bearing mice (4-6 weeks) were treated with S typhimurium carrying plasmids encoding shRNA against gfp or scrambled shRNA. The mRNA and protein expression levels of GFP were assessed 5 d after the bacteria administration, and the antitumor effects of S typhimurium were evaluated.Results: In BTT-T739-GFP tumor-bearing mice, S typhirnurium (1×109 cfu, po) preferentially accumulated within tumors for as long as 40 d, and formed a tumor-to-normal tissue ratio that exceeded 1000/1. S typhimurium carrying plasmids encoding shRNA against gfp inhibited the expression of GFP in tumor cells by 73.4%. Orally delivered S typhimurium significantly delayed tumor growth and prolonged the survival of tumor-bearing mice.Conclusion: This study demonstrates that attenuated S typhimurium can be used for both delivering shRNA-expressing vectors into tumor cells and eliciting RNAi, thus exerting anti-tumor activity, which may represent a new strategy for the treatment of solid tumors.

  6. Ruguo key genes and tumor driving factors identification of bladder cancer based on the RNA-seq profile

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    Zhang M

    2016-05-01

    Full Text Available Minglei Zhang,1 Hongyan Li,2 Di Zou,3 Ji Gao2 1Department of Orthopedics, Division of Tumor and Trauma Surgery, 2Department of Urology, China–Japan Union Hospital of Jilin University, 3Department of Nephrology, The First Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China Aim: This study aimed to select several signature genes associated with bladder cancer, thus to investigate the possible mechanism in bladder cancer.Methods: The mRNA expression profile data of GSE31614, including ten bladder tissues and ten control samples, was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs in bladder cancer samples compared with the control samples were screened using the Student’s t-test method. Functional analysis for the DEGs was analyzed using the Database for Annotation, Visualization, and Integrated Discovery from the Gene Ontology database, followed by the transcription function annotation of DEGs from Tumor-Associated Gene database. Motifs of genes that had transcription functions in promoter region were analyzed using the Seqpos.Results: A total of 1,571 upregulated and 1,507 downregulated DEGs in the bladder cancer samples were screened. ELF3 and MYBL2 involved in cell cycle and DNA replication were tumor suppressors. MEG3, APEX1, and EZH2 were related with the cell epigenetic regulation in bladder cancer. Moreover, HOXB9 and EN1 that have their own motif were the transcription factors.Conclusion: Our study has identified several key genes involved in bladder cancer. ELF3 and MYBL2 are tumor suppressers, HOXB9 and EN1 are the main regulators, while MEG3, APEX1, and EZH2 are driving factors for bladder cancer progression. Keywords: bladder cancer, differentially expressed genes, tumor driving factor, function analysis

  7. Tumor-specific immunotherapy of murine bladder cancer with butanol-extracted antigens and ethylchlorformate polymerized tumor protein.

    Science.gov (United States)

    Rochester, M G; Sarosdy, M F; Pickett, S H; Stogdill, B J; Lamm, D L

    1988-09-01

    Successful treatment of superficial bladder cancer using nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) has been well documented. Investigation of two potential tumor-specific immunotherapeutic agents using a murine transitional-cell carcinoma model (MBT-2) is reported. The survival of mice immunized with tumor proteins obtained by treating tumor cells with either 1-butanol or ethylchlorformate was compared to the survival of animals immunized with BCG. Long-term immunity conferred by each of these agents was also assessed. Significant protection by both agents was noted in all treatment groups compared to controls. Long-term immunity was also found to result from treatment with both investigational agents as well as with BCG. Butanol-extracted antigens and ethylchlorformate polymerized tumor protein may be useful as immunotherapeutic alternatives to BCG. PMID:3411695

  8. Adult urinary bladder tumors with rabdomyosarcomatous differentiation: Clinical, pathological and immunohistochemical studies

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    Zhang Paul J

    2011-07-01

    Full Text Available Abstract Adult rhabdomyosarcoma (RMS in the urinary bladder is rare, and is the subject of case reports and small series. It consists of sheets of small round blue cells with high nuclear cytoplasmic ratio, brisk mitosis and apoptosis. In this study, we reported one case of pure rhabdomyosarcoma and two cases of urothelial carcinomas with extensive rhabdomyosarcomatous differentiation. In addition, their immunohistochemical profile was compared to that of small cell carcinoma of the bladder. Our study showed that sufficient sampling was critical for the diagnosis of urothelial carcinoma with extensive rhabdomyosarcomatous differentiation. As adult RMS in the bladder and urothelial carcinoma with rhabdomyosarcomatous differentiation shared morphological features with small cell carcinoma of the bladder, appropriate immunohistochemical stains were necessary in the differential diagnosis. We showed both rhabdomyosarcoma and rhabdomyosarcomatous areas of the urothelial carcinoma were positive for myogenin, negative for cytokeratin and chromogranin stains. In contrast, small cell carcinoma was positive for cytokeratin, and 7 out of 9 cases were also positive for chromogranin. Both rhabdomyosarcoma and small cell carcinoma could be positive for synaptophysin, a potential pitfall to avoid. In addition, all of the tumors with rhabdomyosarcomatous differentiation were negative for FKHR rearrangement.

  9. Contrast-enhanced computed tomography of the primary tumor in muscle invasive carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Patients with muscle invasive carcinoma of the urinary bladder were examined with contrast-enhanced CT of the primary tumor. A specially designed technique was developed to increase the diagnostic potential of CT. The most important points about the technique were controlled filling of the bladder, the use of thin slices, series of scans before and after intravenous injection of contrast medium, and long scanning times in the precontrast series. The absorbed dose to the patient resulting from the new technique was found to be within the range of the dose from urography or barium enema. This dose was considered to be acceptable given the diagnostic gain of the procedure. Features of irradiated bladder tumors were analysed to find which parameter correlated with persistent malignancy. High contrast enhancement of a tumor relative to the bladder wall was found to be the best indicator of a malignant tumour after irradiation. 127 refs

  10. Perioperative search for circulating tumor cells in patients undergoing radical cystectomy for bladder cancer

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    Karl A

    2009-11-01

    Full Text Available Abstract Objective Despite having an organ confined tumor stage at the time of radical cystectomy, a certain number of bladder cancer patients will develop local or distant metastases over time. Currently there are no reliable serum markers for monitoring and evaluating risk profiles of urothelial cancers. Several studies suggest that detection of Circulating Tumor Cells (CTC may correlate with disease status and prognosis at baseline and early in the treatment of cancers. The presence of CTCs in whole blood before and during radical cystectomy could provide further information on disease status, and could be used as an indicator to determine the need for adjuvant or even perioperative chemotherapy. Methods From 03/2009 to 05/2009, five patients with histologically proven transitional cell carcinoma of the urinary bladder participated in this study. All patients were admitted to the hospital for radical cystectomy (rCx. A standard or extended lymph node dissection was performed in all cases. Preoperative CT or MRI scans revealed no distant or local metastases. Median age was 66.8 years (55-81 yrs. After obtaining informed consent from each patient, approximately 30 mL of peripheral blood was taken immediately before rCx and again during surgical removal of the urinary bladder from the patients' body. As additional parameters, operation time (OR for surgical removal of the bladder and the amount of blood volume that was used for the detection of CTCs were recorded. Obtained blood samples were processed using the Cell-Search System (Veridex© within 48 hours of collection. CTCs were identified and quantitated using the Cell-Search System, followed by re-evaluation of the provided results by specially trained and experienced personal. (CS, SH Results CTCs were detected before and during surgical removal of the urinary bladder in one of five patients (20%. In the one patient positive for CTC, two CTCs were detected in the blood sample that was

  11. Evaluation of Urinary Nuclear Matrix Protein-22 as Tumor Marker Versus Tissue Polypeptide Specific Antigen in Bilharzial and Bladder Cancer

    International Nuclear Information System (INIS)

    Urinary nuclear matrix protein-22 (NMP-22) and tissue polypeptide specific antigen (TPS) were determined as potential marker for early detection of bladder tumors in patients with high risk (Bilharzial-patients), monitoring and follow up bladder cancer patients. The objective was to determine sensitivity and specificity of markers for bilharzial and cancer lesions. The levels of two parameters were determined pre and post operation. A total of 110 individuals, 20 healthy, 20 bilharzial patients and 70 bladder cancer patients with confirmed diagnosis were investigated. Urine samples were assayed for NMP-22 and TPS test kits. Some bladder cancer patients were selected to follow up. NMP-22 showed highly significant increase (P,0.001) more than TPS (P<0.01) in bladder cancer patients when compared with bilharzial and control group. Overall sensitivity is 7.8% for TPS and 98.5% for NMP-22

  12. Centrosome clustering and cyclin D1 gene amplification in double minutes are common events in chromosomal unstable bladder tumors

    International Nuclear Information System (INIS)

    Aneuploidy, centrosome abnormalities and gene amplification are hallmarks of chromosome instability (CIN) in cancer. Yet there are no studies of the in vivo behavior of these phenomena within the same bladder tumor. Twenty-one paraffin-embedded bladder tumors were analyzed by conventional comparative genome hybridization and fluorescence in situ hybridization (FISH) with a cyclin D1 gene (CCND1)/centromere 11 dual-color probe. Immunofluorescent staining of α, β and γ tubulin was also performed. Based on the CIN index, defined as the percentage of cells not displaying the modal number for chromosome 11, tumors were classified as CIN-negative and CIN-positive. Fourteen out of 21 tumors were considered CIN-positive. All T1G3 tumors were included in the CIN-positive group whereas the majority of Ta samples were classified as CIN-negative tumors. Centrosome clustering was observed in six out of 12 CIN-positive tumors analyzed. CCND1 amplification in homogeneously staining regions was present in six out of 14 CIN-positive tumors; three of them also showed amplification of this gene in double minutes. Complex in vivo behavior of CCND1 amplicon in bladder tumor cells has been demonstrated by accurate FISH analysis on paraffin-embedded tumors. Positive correlation between high heterogeneity, centrosome abnormalities and CCND1 amplification was found in T1G3 bladder carcinomas. This is the first study to provide insights into the coexistence of CCND1 amplification in homogeneously staining regions and double minutes in primary bladder tumors. It is noteworthy that those patients whose tumors showed double minutes had a significantly shorter overall survival rate (p < 0.001)

  13. Response evaluation criteria of chemotherapy for bladder cancer. Intra-observer and inter-observer variability in measurement of local response with magnetic resonance imaging

    International Nuclear Information System (INIS)

    Various evaluation criteria have been used in clinical trials and clinical practice in chemotherapy for bladder cancer. Although tumor, nodes and metastasis (TNM) staging system is used for bladder cancer with muscular invasion, the standardized criteria are Response Evaluation Criteria In Solid Tumors (RECIST). To date, the use of RECIST for bladder cancer has not been well assessed. We elucidated the intra- and inter-observer reproducibility of the evaluation criteria with magnetic resonance imaging (MRI) in the present retrospective study. Eligible 41 patients had two courses of the chemotherapy. Three investigators evaluated the MRI twice. Four criteria, RECIST, World Health Organization criteria (WHO), modified RECIST (the shortest diameter perpendicular to RECIST), and T-factor were compared using the kappa statistics. Mean intra-observer agreements of these four criteria were 0.81, 0.67, 0.80, and 0.44, respectively. Median inter-observer agreements were 0.82, 0.78, 0.69, and 0.57, respectively. The proportion of agreement of the response between RECIST and modified RECIST was 78% (Spearman's rho=.800) with higher response in modified RECIST. From our findings, modified RECIST is recommended as the preferred criteria for bladder cancer. However, validation should be performed in the future studies comparing the efficacy and clinical outcomes such as survival and pathological findings. (author)

  14. Labelling of anti-human bladder tumor chimeric antibody with 99Tcm and radioimmunoimaging of bladder carcinoma xenograft in nude mice

    International Nuclear Information System (INIS)

    Objective: To study the in vitro immunoreactivity and in vivo tissue distribution, tumor targeting property of anti-human bladder tumor human-murine chimeric antibody (ch-BDI) labeled with 99Tcm and to investigate its possibility for being used in guiding diagnosis and guiding therapy of bladder cancer. Methods: The ch-BDI was labeled with 99Tcm by improved Schwarz method and the labeled antibody was purified by Sephadex G-50. Labeling yield and radiochemical purity were measured by paper chromatography. The immunoreactive fraction and association constant (Ka) were measured by Lindmo method and Scatchard analysis, respectively. 11.1 MBq (30 μg) 99Tcm-ch-BDI was intravenously injected into nude mice bearing human bladder cancer xenografts in the right thigh and radioimmunoimaging (RII) was performed 2, 6, 20 and 24 h postinjection. The images were processed by region of interest (ROI) method to acquire the counts of whole body and the tumor and the counts ratios of tumor to contralateral normal tissue or to tissues of other non-tumor bearing organs. The mice were killed after 24 h postinjection imaging and tissue distribution was measured. %ID/g and target to nontarget (T/NT) ratios were calculated. Results: The labeling yield and radiochemical purity of 99Tcm-ch-BDI were (66.5±7.3)% and >90%, respectively. The immunoreactive fraction was 76% and Ka was 3.56 x 109 L/mol. RII showed that the tumor was clearly visualized 6 h postinjection and becoming clearer along with time prolonging. The radioactivity of whole body decreased rapidly with time, whereas the radioactivity of the tumor decreased slowly. The T/NT ratios was increased with time. Biodistribution results showed that tumor uptake was 17.4%ID/g 24 h postinjection. T/NT ratios were very high except for the kidney. T/NT ratios for brain, muscle, intestinal wall, bone and heart wall were 136.0, 55.1, 39.3, 29.7 and 27.9, respectively. Conclusion: 99Tcm-ch-BDI exhibits excellent immunoreactivity and tumor

  15. Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines

    International Nuclear Information System (INIS)

    The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin

  16. Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment.

    Science.gov (United States)

    Noguera-Ortega, Estela; Blanco-Cabra, Núria; Rabanal, Rosa Maria; Sánchez-Chardi, Alejandro; Roldán, Mónica; Guallar-Garrido, Sandra; Torrents, Eduard; Luquin, Marina; Julián, Esther

    2016-01-01

    The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines' production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID:27265565

  17. Mycobacteria emulsified in olive oil-in-water trigger a robust immune response in bladder cancer treatment

    Science.gov (United States)

    Noguera-Ortega, Estela; Blanco-Cabra, Núria; Rabanal, Rosa Maria; Sánchez-Chardi, Alejandro; Roldán, Mónica; Guallar-Garrido, Sandra; Torrents, Eduard; Luquin, Marina; Julián, Esther

    2016-01-01

    The hydrophobic composition of mycobacterial cell walls leads to the formation of clumps when attempting to resuspend mycobacteria in aqueous solutions. Such aggregation may interfere in the mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve the immunotherapeutic activity of Mycobacterium brumae, we designed different emulsions and demonstrated their efficacy. The best formulation was initially selected based on homogeneity and stability. Both olive oil (OO)- and mineral oil-in-water emulsions better preserved the mycobacteria viability and provided higher disaggregation rates compared to the others. But, among both emulsions, the OO emulsion increased the mycobacteria capacity to induce cytokines’ production in bladder tumor cell cultures. The OO-mycobacteria emulsion properties: less hydrophobic, lower pH, more neutralized zeta potential, and increased affinity to fibronectin than non-emulsified mycobacteria, indicated favorable conditions for reaching the bladder epithelium in vivo. Finally, intravesical OO-M. brumae-treated mice showed a significantly higher systemic immune response, together with a trend toward increased tumor-bearing mouse survival rates compared to the rest of the treated mice. The physicochemical characteristics and the induction of a robust immune response in vitro and in vivo highlight the potential of the OO emulsion as a good delivery vehicle for the mycobacterial treatment of bladder cancer. PMID:27265565

  18. Alternativas Terapéuticas en las neoplasias vesicales caninas Therapeutic options in canine bladder tumors

    Directory of Open Access Journals (Sweden)

    R.L. Rovere

    2002-01-01

    Full Text Available Las neoplasias vesicales en caninos representan menos del 1% de los tumores presentes en esta especie. El tratamiento quirúrgico se indica en tumores benignos y como complemento de la quimioterapia y radioterapia. Para la quimioterapia se emplean más frecuentemente la doxorrubicina, el 5-fluorouracilo, la ciclofosfamida, la vincristina y cisplatino. La asociación de la doxorrubicina-ciclofosfamida por vía sistémica en asociación con el cisplatino intravesical, sería un tratamiento recomendable, en particular en los casos de carcinoma de células de transiciónThe canine urinary bladder tumors represent less than 1% of all tumors present in this species. Surgical treatment is indicated in benign tumors and combined with chemotherapy or radiotherapy. Doxorubicin, 5 fluorouracil, cyclophosphamide, vincristine and cisplatin are the drugs mostly used for chemotherapy. Systemic Doxorubicin-ciclophosphamide therapy in association with intravesical cisplatin therapy are recommended, particularly in transitional cell carcinoma

  19. A study of brain MRI findings and clinical response of bladder empting failure in brain bladder

    Energy Technology Data Exchange (ETDEWEB)

    Miyakoda, Keiichi (Yamashina Aiseikai Hospital, Kyoto (Japan)); Watanabe, Kousuke

    1993-02-01

    In 45 patients (38 males and 7 females; average age:78 years) with brain bladder, who did not have any peripheral neuropathies and spinal disturbance, cerebral findings of MRI (1.5 T) T[sub 2] enhanced image were analyzed in comparison with those of 7 control patients with normal urination after BPH operations. Patients with neurogenic bladder were divided into three groups as follows: 33 patients with a chief complaint of urinary disturbance (Group I), 9 patients with urinary incontinence (Group II) and 3 patients with balanced bladder (Group III). High frequency of lacune (24%) of the globus pallidus and low signalling of the corpus striatum (30%) was found in Group I patients, but low frequency in other Group patients and control patients. Furthermore, pathologic changes with various grades in the globus pallidus were observed in 91% of Group I patients. In the treatment of urinary disturbance, a high improvement rate of micturition disorder (77%) was obtained in patients treated with a combination of dantrolene and TURp (TUIbn for females). However, patients who had clear lacune of the globus pallidus showed the low improvement rate. It should be possible that the globus pallidus contributes to control the movement of the external sphincter and the pelvic base muscles as well as other striated muscles. Moreover, lacune was rarely found in the urination center of the brain-stem on MRI. (author).

  20. Origins of Bladder Cancer.

    Science.gov (United States)

    Czerniak, Bogdan; Dinney, Colin; McConkey, David

    2016-05-23

    Bladder cancer, one of the most frequently occurring human cancers, develops via two tracks referred to as papillary and nonpapillary that correspond to clinically different forms of the disease. Most bladder cancers are chemically induced, with tobacco smoking being the leading risk factor. Recent advances in bladder cancer research have enhanced our understanding of the origin of this disease from urothelial progenitor cells via field effects along papillary/luminal and nonpapillary/basal pathways. Evident from the outset of the disease, the diversity of the luminal and basal pathways, together with cell lineage tracing studies, postulates the origin of molecularly distinct subtypes from different uroprogenitor cells. The molecular mechanisms initiating field effects involve a new class of genes referred to as forerunner (FR) genes that generally map around major tumor suppressors such as RB1. These genes are silenced, predominantly by hypermethylation and less frequently by mutations, and drive the expansion of intraurothelial preneoplastic cells. Different FR genes are involved in various molecular subtypes of bladder cancer and they sensitize the uroprogenitor cells to the development of luminal and basal bladder cancers in animal models. In human bladder cancer, luminal and basal forms have dissimilar clinical behavior and response to conventional and targeted chemotherapeutic manipulations. These new research developments hold the promise of expanding our armamentarium of diagnostic and treatment options for patients with bladder cancer and improving our ability to select patients most likely to respond to a specific therapy. PMID:26907529

  1. Effects of tumor necrosis factor-alpha and interferon-gamma on expressions of matrix metalloproteinase-2 and -9 in human bladder cancer cells.

    Science.gov (United States)

    Shin, K Y; Moon, H S; Park, H Y; Lee, T Y; Woo, Y N; Kim, H J; Lee, S J; Kong, G

    2000-10-31

    We have investigated the effects of tumor necrosis factor-alpha (TNF-alpha) and interferon (INF-gamma), the potent Bacillus Calmette-Guerin (BCG)-induced cytokines on the production of MMP-2, MMP-9, TIMP-1, TIMP-2 and MT1-MMP in high grade human bladder cancer cell lines, T-24, J-82 and HT-1376 cell lines. MMP-2 expression and activity were decreased in T-24 cells treated with both cytokines in a dose dependent manner. However, J-82 cells treated with TNF-alpha and INF-gamma revealed dose dependent increases of MMP-9 expression and activity with similar baseline expression and activity of MMP-2. HT-1376 cells after exposure to TNF-alpha only enhanced the expression and activity of MMP-9. These results indicate that TNF-alpha and INF-gamma could regulate the production of MMP-2 or MMP-9 on bladder cancer cells and their patterns of regulation are cell specific. Furthermore, this diverse response of bladder cancer cells to TNF-alpha and INF-gamma suggests that BCG immunotherapy may enhance the invasiveness of bladder cancer in certain conditions with induction of MMPs. PMID:10996723

  2. Bovine Papillomavirus Type 2 Infection and a Series of Mesenchymal Tumors of the Urinary Bladder in Cattle

    Directory of Open Access Journals (Sweden)

    Manuela Martano

    2013-01-01

    Full Text Available This report describes the histopathology of two hundred and fifty-three mesenchymal tumors of the urinary bladder in cattle grazing on lands rich in bracken fern. Approximately 80% were hemangiomas and angiosarcomas. Hemangioma (capillary, cavernous, and large vessels was the most frequent mesenchymal tumor and was more common than angiosarcoma. Although the appearance of endothelial cells can vary remarkably, epithelioid angiosarcomas, often containing multinucleated cells, were the most frequent malignant vascular tumors. Hemangiopericytoma and tumors of muscle and soft connective tissue origin, alone and/or in association with tumor-like lesions, were less frequently seen. Furthermore, forty-five cases of intravascular papillary endothelial hyperplasia (IPEH, a lesion not previously reported in the urinary bladder of cattle, were also described. Bovine papillomavirus type-2 DNA was amplified in tumor samples. Forty vascular tumors were investigated by dual-labeling immunofluorescence, and, for the first time, a coexpression of E5 and platelet-derived growth factor β receptor (PDGFβR was shown to occur. The results show that the BPV-2 E5 oncoprotein binds to the activated form of the PDGFβ receptor thus playing an important role in mesenchymal as well as epithelial carcinogenesis of the urinary bladder. Furthermore, these findings demonstrate that BPV-2 infects both epithelial and mesenchymal cells.

  3. Evaluation of the performance of a p53 sequencing microarray chip using 140 previously sequenced bladder tumor samples

    DEFF Research Database (Denmark)

    Wikman, Friedrik; Lu, Ming-Lan; Andersen, Thomas Thykjær;

    2000-01-01

    available chip and describes a method to increase the specificity of the chip. Methods: DNA from 140 human bladder tumors was extracted and subjected to a multiplex-PCR before loading onto the p53 GeneChip from Affymetrix. The same samples were previously sequenced by manual dideoxy sequencing. In addition...

  4. Human Adipose Derived Stem Cells Induced Cell Apoptosis and S Phase Arrest in Bladder Tumor

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2015-01-01

    Full Text Available The aim of this study was to determine the effect of human adipose derived stem cells (ADSCs on the viability and apoptosis of human bladder cancer cells. EJ and T24 cells were cocultured with ADSCs or cultured with conditioned medium of ADSCs (ADSC-CM, respectively. The cell counting and colony formation assay showed ADSCs inhibited the proliferation of EJ and T24 cells. Cell viability assessment revealed that the secretions of ADSCs, in the form of conditioned medium, were able to decrease cancer cell viability. Wound-healing assay suggested ADSC-CM suppressed migration of T24 and EJ cells. Moreover, the results of the flow cytometry indicated that ADSC-CM was capable of inducing apoptosis of T24 cells and inducing S phase cell cycle arrest. Western blot revealed ADSC-CM increased the expression of cleaved caspase-3 and cleaved PARP, indicating that ADSC-CM induced apoptosis in a caspase-dependent way. PTEN/PI3K/Akt pathway and Bcl-2 family proteins were involved in the mechanism of this reaction. Our study indicated that ADSCs may provide a promising and practicable manner for bladder tumor therapy.

  5. Total intravenous general anesthesia with laryngeal mask airway for transurethral resection of bladder tumor

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To observe the advantage of total intravenous anesthesia for transurethral resection of bladder tumor (TURBT). Methods: Sixty ASA Ⅰ-Ⅱ patients undergoing TURBT were randomly assigned to 2 groups. Spinal anesthesia with 0.75% pure bupivacaine (8-12 mg) was applied to patients in Group Ⅰ (n= 30). Patients in Group Ⅱ (n=30) received total intravenous anesthesia with continuous infusion of Propofol and Remifentanil; and a laryngeal mask was used to ensure the airway and ventilation. BP, HR, SPO2 and pertinent side effects were monitored and recorded. Results: The patients in group Ⅱ experienced more stable hemodynamics than those in group Ⅰ. Obturator nerve reflex was observed in 15 (50.0%) patients in Group Ⅰ, but none (0%) in Group Ⅱ (P<0.01). Conclusion: Total intravenous anesthesia with laryngeal mask is a safe, reliable, controllable and simple manual for patient undergoing TURBT.

  6. Activation of Nerve Growth Factor-Induced Bα by Methylene-Substituted Diindolylmethanes in Bladder Cancer Cells Induces Apoptosis and Inhibits Tumor GrowthS⃞

    OpenAIRE

    Dae Cho, Sung; Lee, Syng-Ook; Chintharlapalli, Sudhakar; Abdelrahim, Maen; Khan, Shaheen; Yoon, Kyungsil; Kamat, Ashish M.; Safe, Stephen

    2010-01-01

    Nerve growth factor-induced B (NGFI-B) genes are orphan nuclear receptors, and NGFI-Bα (Nur77, TR3) is overexpressed in bladder tumors and bladder cancer cells compared with nontumorous bladder tissue. 1,1-Bis(3′-indolyl)-1-(p-methoxyphenyl)-methane (DIM-C-pPhOCH3) and 1,1-bis(3′-indolyl)-1-(p-phenyl)methane have previously been identified as activators of Nur77, and both compound...

  7. Independent Component Analysis Uncovers the Landscape of the Bladder Tumor Transcriptome and Reveals Insights into Luminal and Basal Subtypes

    Directory of Open Access Journals (Sweden)

    Anne Biton

    2014-11-01

    Full Text Available Extracting relevant information from large-scale data offers unprecedented opportunities in cancerology. We applied independent component analysis (ICA to bladder cancer transcriptome data sets and interpreted the components using gene enrichment analysis and tumor-associated molecular, clinicopathological, and processing information. We identified components associated with biological processes of tumor cells or the tumor microenvironment, and other components revealed technical biases. Applying ICA to nine cancer types identified cancer-shared and bladder-cancer-specific components. We characterized the luminal and basal-like subtypes of muscle-invasive bladder cancers according to the components identified. The study of the urothelial differentiation component, specific to the luminal subtypes, showed that a molecular urothelial differentiation program was maintained even in those luminal tumors that had lost morphological differentiation. Study of the genomic alterations associated with this component coupled with functional studies revealed a protumorigenic role for PPARG in luminal tumors. Our results support the inclusion of ICA in the exploitation of multiscale data sets.

  8. Bovine Papillomavirus Type 2 Infection and Microscopic Patterns of Urothelial Tumors of the Urinary Bladder in Water Buffaloes

    Directory of Open Access Journals (Sweden)

    Paola Maiolino

    2013-01-01

    Full Text Available Microscopic patterns of thirty-four urothelial tumors of the urinary bladder of water buffaloes from the Marmara and Black Sea Regions of Turkey are here described. All the animals grazed on lands rich in bracken fern. Histological diagnosis was assessed using morphological parameters recently suggested for the urinary bladder tumors of cattle. Papillary carcinoma was the most common neoplastic lesion (22/34 observed in this study, and low-grade carcinoma was more common (seventeen cases than high-grade carcinoma (five cases. Papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP, and invasive carcinomas were less frequently seen. Carcinoma in situ (CIS was often detected associated with some papillary and invasive carcinomas. De novo (primary CIS was rare representing 3% of tumors of this series. A peculiar feature of the most urothelial tumors was the presence in the tumor stroma of immune cells anatomically organized in tertiary lymphoid organs (TLOs. Bovine papillomavirus type-2 (PV-2 E5 oncoprotein was detected by molecular and immunohistochemistry procedures. Early protein, E2, and late protein, L1, were also detected by immunohistochemical studies. Morphological and molecular findings show that BPV-2 infection contributes to the development of urothelial bladder carcinogenesis also in water buffaloes.

  9. Genetic Evidence in Melanoma and Bladder Cancers that p16 and p53 Function in Separate Pathways of Tumor Suppression

    OpenAIRE

    Gruis, Nelleke A.; Weaver-Feldhaus, Jane; Liu, Qingyun; Frye, Cheryl; Eeles, Rosalind; Orlow, Irene; Lacombe, Louis; Ponce-Castaneda, Veronica; Lianes, Pilar; Latres, Esther; Skolnick, Mark; Cordon-Cardo, Carlos; Kamb, Alexander

    1995-01-01

    The 9p21 region of human chromosome 9 is a hot spot for chromosomal aberrations in both cultured cell lines and primary tumors. This region contains a gene, P16 (also called MTS1, CDKN2 and p16INK4), that encodes a presumptive negative cell cycle regulator called p16. P16 is deleted or mutated at high frequency in a variety of tumor cell lines including melanoma and bladder carcinoma lines. As such, it is likely to be a tumor suppressor gene. Here we show that P16 is mutated in primary bladde...

  10. Bladder tumors:dynamic contrast-enhanced axial imaging, multiplanar reformation, three-dimensional reconstruction and virtual cystoscopy using helical CT

    Institute of Scientific and Technical Information of China (English)

    王东; 张挽时; 熊明辉; 喻敏; 徐家兴

    2004-01-01

    Background There have been few studies to evaluate the effects of helical CT on bladder tumor. This study was to evaluate the clinical applications of helical CT dynamic contrast-enhanced axial imaging, multiplanar reformation (MPR), three-dimensional (3D) reconstruction and virtual cystoscopy (CTVC) in bladder tumors. Methods The precontrast and four-phase postcontrast helical CT scans were performed in 42 patients with bladder tumors confirmed by conventional cystoscopy and pathology. MPR, 3D and CTVC images were generated from the volumetric data of the excretory phase. The results were then compared with the findings of conventional cystoscopy and surgery in a double-blinded mode. Results The sensitivity of the axial, 3D and CTVC images in detecting the bladder tumors were 90.8%, 76.9% and 95.4% respectively. The dynamic contrast-enhanced axial images could provide excellent intramural and extravesical information, and the accuracy in preoperative tumor staging was 87.7%. MPR could directly demonstrate the origin and extravesical invasions of the tumors and their relation to the ureter. 3D and CTVC images were useful for displaying the surface morphology of the tumor and the relationship between the tumor and the ureteric orifices, whereas CTVC could depict the tumors smaller than 5 mm that were not seen on the axial images.Conclusions The combination of axial, MPR, 3D and CTVC images with helical CT can provide comprehensive information on bladder tumor.

  11. Independent position correction on tumor and lymph nodes; consequences for bladder cancer irradiation with two combined IMRT plans

    International Nuclear Information System (INIS)

    The application of lipiodol injections as markers around bladder tumors combined with the use of CBCT for image guidance enables daily on-line position correction based on the position of the bladder tumor. However, this might introduce the risk of underdosing the pelvic lymph nodes. In this study several correction strategies were compared. For this study set-up errors and tumor displacements for ten complete treatments were generated; both were based on the data of 10 bladder cancer patients. Besides, two IMRT plans were made for 20 patients, one for the elective field and a boost plan for the tumor. For each patient 10 complete treatments were simulated. For each treatment the dose was calculated without position correction (option 1), correction on bony anatomy (option 2), on tumor only (option 3) and separately on bone for the elective field (option 4). For each method we analyzed the D99% for the tumor, bladder and lymph nodes and the V95% for the small intestines, rectum, healthy part of the bladder and femoral heads. CTV coverage was significantly lower with options 1 and 2. With option 3 the tumor coverage was not significantly different from the treatment plan. The ΔD99% (D99%, option n - D99%, treatment plan) for option 4 was small, but significant. For the lymph nodes the results from option 1 differed not significantly from the treatment plan. The median ΔD99% of the other options were small, but significant. ΔD99% for PTVbladder was small for options 1, 2 and 4, but decreased up to -8.5 Gy when option 3 was applied. Option 4 is the only method where the difference with the treatment plan never exceeds 2 Gy. The V95% for the rectum, femoral heads and small intestines was small in the treatment plan and this remained so after applying the correction options, indicating that no additional hot spots occurred. Applying independent position correction on bone for the elective field and on tumor for the boost separately gives on average the best target

  12. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26). CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests

  13. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Koutsilieris Michael

    2011-08-01

    Full Text Available Abstract Background The diagnostic value and prognostic significance of circulating tumor cell (CTC detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Methods Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+ and negative likelihood ratios (LR- of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Results Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%; specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%, 3.77 (95%CI, 1.95-7.30 and 0.72 (95%CI, 0.64-0.81. CTC-positive patients were significantly more likely to have advanced (stage III-IV disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26. Conclusions CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests.

  14. Acrolein- and 4-Aminobiphenyl-DNA adducts in human bladder mucosa and tumor tissue and their mutagenicity in human urothelial cells

    OpenAIRE

    Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Hu, Yu; Chen, Wei-Sheng; Chou, David; Yan LIU; Donin, Nicholas; Huang, William C; Lepor, Herbert; Wu, Xue-Ru; Wang, Hailin; Beland, Frederick A.; Tang, Moon-shong

    2014-01-01

    Tobacco smoke (TS) is a major cause of human bladder cancer (BC). Two components in TS, 4-aminobiphenyl (4-ABP) and acrolein, which also are environmental contaminants, can cause bladder tumor in rat models. Their role in TS related BC has not been forthcoming. To establish the relationship between acrolein and 4-ABP exposure and BC, we analyzed acrolein-deoxyguanosine (dG) and 4-ABP-DNA adducts in normal human urothelial mucosa (NHUM) and bladder tumor tissues (BTT), and measured their mutag...

  15. The role of succinylcholine in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors

    International Nuclear Information System (INIS)

    Objective was to present our 8 year experience in the prevention of the obturator nerve reflex during transurethral resection of bladder tumors. This study was performed in Ataturk University Hospital between 1999 and 2007. We retrospectively reviewed the records of 89 patients with inferolateral bladder tumors, who underwent transurethral resection under epidural or general anesthesia and requested obturator nerve reflex inhibition. Epidural anesthesia was administered to 57 patients, while the remaining 32 patients underwent general anesthesia via mask; and succinylcholine was administered prior to resection. Of the 57 patients received epidural anesthesia, 18 were diagnosed as inferolateral bladder tumors during endoscopy and had to undergo general anesthesia. Obturator nerve block was attempted preoperatively in 39 patients. However, a nerve identification failure, hematoma and 4 obturator nerve reflex events, despite the block, were observed and these patients were subjected to general anesthesia with succinylcholine. Fifty-six patients (32 patients initially had general anesthesia and 24 converted from epidural to general anesthesia) were all given succinylcholine prior to resection. Due to its mechanisms of action, succinylcholine is completely effective and represents a simple alternative to obturator nerve block. No contraction was observed in any patient given succinylcholine. (author)

  16. Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors

    Directory of Open Access Journals (Sweden)

    Pop LA

    2016-06-01

    Full Text Available Laura A Pop,1,* Valentina Pileczki,1,2,* Roxana M Cojocneanu-Petric,1 Bogdan Petrut,3,4 Cornelia Braicu,1 Ancuta M Jurj,1 Rares Buiga,5 Patriciu Achimas-Cadariu,6,7 Ioana Berindan-Neagoe1,8 1The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 2Department of Analytical Chemistry, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 3Department of Surgery II – Urology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 4Department of Urology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 5Department of Pathology, The Oncology Institute “Prof. Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 6Department of Surgery, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 7Department of Surgical Oncology and Gynecological Oncology, Iuliu Haţieganu University of Medicine and Pharmacy, 8Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania *These authors contributed equally to this work Background: Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors. Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods: The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three

  17. [Descriptive study of bladder tumors in the district of Levante-Alto Almanzora].

    Science.gov (United States)

    Hita Rosino, E; Jiménez Verdejo, A; Mellado Mesa, P; López Hidalgo, J; Sánchez Fornieles, E; Grau Civit, J

    2001-06-01

    We present our series of operater bladder cancers in this District and the annual incidence in the period 1996 at 1998, as web as they are distributed by sex, age and smoking in the population; neoplasic stage and relapse were also studied. 61 patients were treated and un found global half incidence of 19.8 for 10(5) inhabitant-year (h-a), while for sexes it was of 4.22 for 10(5) h-y for women and of 15.58 for 10(5) h-y males. 78.69% was male with a masculinity rate of 3.69. The most frequent age group was starting from the seventh decade with 50.81% of our series. There was 36% of intervened patients that they were smoking, while 29.5% had relationship with other factors of risk like hydrocarbons and pesticidas. The superficial tumors were the most frequent with 86.88% of the cases, on the other hand the undifferentiated neoplastics was not very frequent with 13.21%, increasing these neoplastics with the age. In the follow up there were relapses in 36% of the people, being bigger in the T1 of our series. The occupational factors in this district can explain the high frequency in the female sex, although analytic studies are needed to check it. PMID:11512509

  18. Characterization of bladder sensory neurons in the context of myelination, receptors for pain modulators, and acute responses to bladder inflammation

    OpenAIRE

    Shelley L Forrest; Osborne, Peregrine B.; Keast, Janet R.

    2013-01-01

    Bladder sensation is mediated by lumbosacral dorsal root ganglion neurons and is essential for normal voiding and nociception. Numerous electrophysiological, structural and molecular changes occur in these neurons following inflammation. Defining which neurons undergo these changes is critical for understanding the mechanism underlying bladder pain and dysfunction. Our first aim was to define the chemical classes of bladder sensory neurons that express receptors for the endogenous modulators ...

  19. Prospective evaluation of the effect of ionizing radiation on the bladder tumor-associated (BTA) urine test

    International Nuclear Information System (INIS)

    Purpose: To prospectively evaluate the effect of ionizing radiation on the results of the bladder tumor-associated antigen (BTA) test. By examining this question, we sought to determine its potential use as a monitoring test for the detection of recurrent transitional carcinoma of the bladder in patients who have received prior radiotherapy for bladder preservation. Materials and Methods: Between February 1996 and April 1997, 18 patients with nonbladder pelvic malignancies and no history of bladder cancer, received irradiation to the bladder. These patients were prospectively evaluated using the BTA test at the end of the external-beam radiation (EBRT) and at 3-month follow-up intervals. Urine cytology was analyzed in 16 of the 18 patients at the end of EBRT. A median of 3 separate measurements were made (range 1-6) on each patient. The median dose of EBRT was 50.4 Gy (range 30-68Gy). Seven patients underwent brachytherapy as part of their treatment course. BTA results and time intervals were recorded and analyzed using univariate and Kaplan-Meyer methodologies. Results: A total of 10 (56%) of the 18 patients had a positive BTA test at some time following completion of EBRT. Of the 10 positive tests, 9 returned to negative in a median of 42 weeks from completion of EBRT. Treatment with chemotherapy, brachytherapy, calculated bladder dose, and total external beam dose did not significantly influence either the number of positive tests or the time to resolution of the positive test in this small group of patients. All screened urine samples were negative for malignant cells and 11 (69%) of 16 showed changes consistent with ionizing radiation. Conclusion: Our findings support the hypothesis that ionizing radiation can cause transient positive results in the BTA test, but that these normalize with time. Although it requires further testing, it seems that the BTA test may be useful in the detection of recurrence in patients with bladder cancer who have been treated with

  20. Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Guancial

    Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

  1. Loss of the urothelial differentiation marker FOXA1 is associated with high grade, late stage bladder cancer and increased tumor proliferation.

    Directory of Open Access Journals (Sweden)

    David J DeGraff

    Full Text Available Approximately 50% of patients with muscle-invasive bladder cancer (MIBC develop metastatic disease, which is almost invariably lethal. However, our understanding of pathways that drive aggressive behavior of MIBC is incomplete. Members of the FOXA subfamily of transcription factors are implicated in normal urogenital development and urologic malignancies. FOXA proteins are implicated in normal urothelial differentiation, but their role in bladder cancer is unknown. We examined FOXA expression in commonly used in vitro models of bladder cancer and in human bladder cancer specimens, and used a novel in vivo tissue recombination system to determine the functional significance of FOXA1 expression in bladder cancer. Logistic regression analysis showed decreased FOXA1 expression is associated with increasing tumor stage (p<0.001, and loss of FOXA1 is associated with high histologic grade (p<0.001. Also, we found that bladder urothelium that has undergone keratinizing squamous metaplasia, a precursor to the development of squamous cell carcinoma (SCC exhibited loss of FOXA1 expression. Furthermore, 81% of cases of SCC of the bladder were negative for FOXA1 staining compared to only 40% of urothelial cell carcinomas. In addition, we showed that a subpopulation of FOXA1 negative urothelial tumor cells are highly proliferative. Knockdown of FOXA1 in RT4 bladder cancer cells resulted in increased expression of UPK1B, UPK2, UPK3A, and UPK3B, decreased E-cadherin expression and significantly increased cell proliferation, while overexpression of FOXA1 in T24 cells increased E-cadherin expression and significantly decreased cell growth and invasion. In vivo recombination of bladder cancer cells engineered to exhibit reduced FOXA1 expression with embryonic rat bladder mesenchyme and subsequent renal capsule engraftment resulted in enhanced tumor proliferation. These findings provide the first evidence linking loss of FOXA1 expression with histological subtypes

  2. The role of PD-L1 in the radiation response and clinical outcome for bladder cancer

    OpenAIRE

    Chun-Te Wu; Wen-Cheng Chen; Ying-Hsu Chang; Wei-Yu Lin; Miao-Fen Chen

    2016-01-01

    Identification of potential factors that can stratify a tumor’s response to specific therapies will aid in the selection of cancer therapy. The aim was to highlight the role of programmed cell death 1 ligand 1 (PD-L1) in bladder cancer. In this study, 92 of muscle-invasive bladder cancers and 28 of non- muscle invasive bladder cancers were selected for immunohistochemical staining analysis. Furthermore, human and murine bladder cancer cell lines were used to examine the correlation between PD...

  3. VALIDATION OF NEUROTENSIN TETRA-BRANCHED PEPTIDES AS TUMOR TARGETING AGENTS IN PANCREAS, COLON AND BLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. Ravenni

    2012-05-01

    Full Text Available The identification of new tumor targeting agents, which might allow either cancer cell tracing or ther- apy, is a crucial issue in cancer research. Membrane receptors for endogenous peptides such as neu- rotensin, somatostatin, bombesin and many others are over-expressed in different human cancers and could therefore be targeted as tumor-specific antigens. In the meantime the extremely short half-life of pep- tides impeded their development for effective pep- tide-based tumor targeting strategies. We synthesized tetra-branched neurotensin peptides (NT4, which ensure extremely long half-life main- taining peptide specificity and increasing avidity through multimeric binding. Moreover this bio-syn- thetical strategy allows a considerable modularity of peptides through the conjugation of different func- tional unit, such as fluorophore, radioactive moieties or chemotherapeutic drugs. Aim of our studies is to validate NT4 for cancer cell tracing in different human tumors. In this view we use fluorophore-conjugated NT4 to discriminate be- tween tumor and healthy tissue obtained by surgical samples from pancreas, colon and bladder carcinoma. Peptide binding on tumor and healthy biopsies was measured in each patient by quantitative analysis of confocal microscopy images. These results show a considerable difference in fluorescence emission be- tween healthy and tumor samples in colon, pancreas and bladder cancer, opening the way to the develop- ment of NT4 as selective diagnostic tools for these pathologies. Moreover our peptides can be conju- gated with different chemotherapeutic moieties in order to allow the selective killing of tumor cells.

  4. TOX3 (TNRC9) overexpression in bladder cancer cells decreases cellular proliferation and triggers an interferon-like response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Mansilla, Francisco; Andersen, Lars Dyrskjøt; Thorsen, Kasper; Fristrup, Niels; Brems-Eskildsen, Anne Sofie; Madsen, Pia Pinholt; Sørensen, Karina Dalsgaard; Borre, Michael; Ørntoft, Torben Falck

    2013-01-01

    cell extracts with an artificial “GAS”-DNA element resulted in an enrichment of the GAS containing DNA-sequence, providing evidence for a potential interaction of TOX3 with the GAS-sequence of STAT1. Conclusions These results provide evidence for an alternative activation of the downstream interferon......Background Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+-dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes and...... identification and immunoprecipitation studies were used for DNA binding studies. Results Microarray transcript profiling of 89 bladder biopsies showed a significant upregulation of TOX3 (p< 10-4) in non-muscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...

  5. TOX3 (TNRC9) Over Expression in Bladder Cancer Cells Decreases Cellular Proliferation and Triggers an Interferon-Like Response

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Mansilla Castaño, Francisco; Dyrskjøt, Lars;

    2013-01-01

    identification and immunoprecipitation studies were used for DNA binding studies. Results: Microarray transcript profiling of 89 bladder biopsies showed a significant up-regulation of TOX3 (p<10-4) in non-muscle invasive (Ta-T1) bladder tumors compared to muscle-invasive (T2-T4) bladder tumors and normal...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS...... expressing cell extracts with an artificial “GAS”- DNA element resulted in an enrichment of the GAS containing DNA-sequence, providing evidence for a potential interaction of TOX3 with the GAS-sequence of STAT1. Conclusions: These results provide evidence for an alternative activation of the downstream...

  6. Bladder Tumor Recurrence after Primary Surgery for Transitional Cell Carcinoma of the Upper Urinary Tract

    OpenAIRE

    Oehlschläger, Sven; Baldauf, Anka; Wiessner, Diana; Gellrich, Jörg; Hakenberg, Oliver W; Wirth, Manfred P.

    2014-01-01

    Objective: Primary transitional cell carcinoma (TCC) of the upper urinary tract represents 6–8% of all TCC cases. Nephroureterectomy with removal of a bladder cuff is the treatment of choice. The rates of TCC recurrence in the bladder after primary upper urinary tract surgery described in the literature range between 12.5 and 37.5%. In a retrospective analysis we examined the occurrence of TCC after nephroureterectomy for upper tract TCC in patients without a previous history of bladder TCC a...

  7. Design of peptide-conjugated glycol chitosan nanoparticles for near infrared fluorescent (NIRF) in vivo imaging of bladder tumors

    Science.gov (United States)

    Key, Jaehong; Dhawan, Deepika; Knapp, Deborah W.; Kim, Kwangmeyung; Kwon, Ick Chan; Choi, Kuiwon; Leary, James F.

    2012-03-01

    Enhanced permeability and retention (EPR) effects for tumor treatment have been utilized as a representative strategy to accumulate untargeted nanoparticles in the blood vessels around tumors. However, the EPR effect itself was not sufficient for the nanoparticles to penetrate into cancer cells. For the improvement of diagnosis and treatment of cancer using nanoparticles, many more nanoparticles need to specifically enter cancer cells. Otherwise, can leave the tumor area and not contribute to treatment. In order to enhance the internalization process, specific ligands on nanoparticles can help their specific internalization in cancer cells by receptor-mediated endocytosis. We previously developed glycol chitosan based nanoparticles that suggested a promising possibility for in vivo tumor imaging using the EPR effect. The glycol chitosan nanoparticles showed a long circulation time beyond 1 day and they were accumulated predominantly in tumor. In this study, we evaluated two peptides for specific targeting and better internalization into urinary bladder cancer cells. We conjugated the peptides on to the glycol chitosan nanoparticles; the peptide-conjugated nanoparticles were also labeling with near infrared fluorescent (NIRF) dye, Cy5.5, to visualize them by optical imaging in vivo. Importantly real-time NIRF imaging can also be used for fluorescence (NIRF)-guided surgery of tumors beyond normal optical penetration depths. The peptide conjugated glycol chitosan nanoparticles were characterized with respect to size, stability and zeta-potential and compared with previous nanoparticles without ligands in terms of their internalization into bladder cancer cells. This study demonstrated the possibility of our nanoparticles for tumor imaging and emphasized the importance of specific targeting peptides.

  8. Adult urinary bladder tumors with rabdomyosarcomatous differentiation: Clinical, pathological and immunohistochemical studies

    OpenAIRE

    Zhang Paul J; Bing Zhanyong

    2011-01-01

    Abstract Adult rhabdomyosarcoma (RMS) in the urinary bladder is rare, and is the subject of case reports and small series. It consists of sheets of small round blue cells with high nuclear cytoplasmic ratio, brisk mitosis and apoptosis. In this study, we reported one case of pure rhabdomyosarcoma and two cases of urothelial carcinomas with extensive rhabdomyosarcomatous differentiation. In addition, their immunohistochemical profile was compared to that of small cell carcinoma of the bladder....

  9. Promotion in urinary bladder carcinogenesis.

    OpenAIRE

    Cohen, S M

    1983-01-01

    Aromatic amines, including 2-naphthylamine, 4-aminobiphenyl and benzidine, are known urinary bladder carcinogens in man and other species, but in rodents, aromatic amines and amides have usually induced liver tumors, occasionally also with tumors of the bladder and other tissues. Variations in organ specificity are related to differences in metabolism; for the production of bladder tumors, the rates of acetylation and deacetylation appear to be critical. Bladder specific carcinogens in rodent...

  10. Feasibility of laser-integrated high intensity focused ultrasound (HIFU) treatment for bladder tumors: in vitro study (Conference Presentation)

    Science.gov (United States)

    Nguyen, Van Phuc; Park, Suhyun; Oh, Junghwan; Kang, Hyun Wook

    2016-02-01

    Previous studies have shown that photothemal therapy combined with high intensity focused ultrasound (HIFU) can provide a promising method to achieve rapid thermal coagulation during surgical procedures. The current study investigated the feasibility of the laser-integrated high intensity focused ultrasound (HIFU) application to treat bladder tumors by enhancing thermal effects and therapeutic depth in vitro. To generate thermal coagulation, a single element HIFU transducer with a central frequency of 2.0 MHz was used to transmit acoustic energy to 15 fresh porcine bladders injected with an artificial tumor (100 µl gelatin and hemoglobin solution) in vitro. Simultaneously, an 80-W 532-nm laser system was also implemented to induce thermal necrosis in the targeted tissue. The intensity of 570 W/cm2 at the focus of HIFU and laser energy of 0.9 W were applied to all the samples for 40 s. The temperature rise increased up to about 1.6 or 3 folds (i.e., ΔT=32±3.8 K for laser-integrated HIFU, ΔT=20±6.5 K for HIFU only, and ΔT=11±5.6 K for laser only). The estimated lesion depth also increased by 1.3 and 2 folds during the dual-thermal treatment, in comparison with the treatment by either HIFU or laser. The results indicated that the laser-integrated HIFU treatment can be an efficient hyperthermic method for tumor coagulation.

  11. Are tumor-to-tumor differences in oxygenation responsible for the heterogeneity in the response of tumors to therapy

    International Nuclear Information System (INIS)

    Individual tumors from the same transplanted tumor line often show very different responses to the same treatments, even when the tumors are implanted into similar sites in similar hosts and studied at the same time. The cause of this heterogeneity is unknown; either tumor or host factors could be responsible. Solid tumors contain large numbers of viable hypoxic cells, which are resistant to both radiotherapy and chemotherapy and limit the response of tumors to intensive treatments. To determine whether differences in the proportion of hypoxic cells in the tumors produce the observed variability in therapeutic sensitivity, the authors compared the radiation responses of normally-aerated tumors and tumors made artificially hypoxic. If large tumor-to-tumor differences in oxygenation exist, data from normally-aerated tumors should be more variable than data from hypoxic tumors (which should all be brought to uniform hypoxia and uniform radioresistance). Analysis of data from several tumor systems revealed the variability in the radiation responses of hypoxic tumors to be at least as great as that for aerobic tumors. Thus, factors other than differences in oxygenation must produce the heterogeneity in tumor radiation response

  12. Radiation responses of human bladder cancer assessed in vitro or as xenografts in immune-deprived mice

    International Nuclear Information System (INIS)

    The response to radiation of cells derived from transitional cell carcinoma (TCC) of the human bladder has been studied. In vitro radiation survival curves for two established cell lines, RT-4 and MGH-U1, and for a cell line HB-10 derived recently from biopsy of a metastatic lymph node were characterized by values of D0 and anti n in the range of 1.1-1.5 Gy and 2-7 respectively. The oxygen enhancement ratio of HB-10 cells was 2.8. Xenografts derived from the line HB-10 were irradiated in vivo under both aerobic and hypoxic conditions and cell survival was assessed in agar. Both aerobic and hypoxic survival curves were similar to that obtained for irradiation of hypoxic HB-10 cells in culture. Another tumor line, HB-15, derived from a cystoscopic biopsy of primary TCC, was maintained by transplantation of xenografts. Regrowth curves for HB-15 xenografts after radiation doses of 10 or 20 Gy were parallel to the growth curve for untreated controls but with volume reduced by factors of about 5 and 20 respectively. Cells derived from TCC of the human bladder exhibit parameters of radiation survival similar to those of other mammalian cells, and that xenografts derived from such cells contain a high proportion of hypoxic cells

  13. Assessment of angiogenic factor, vascular endothelial growth factor, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical Bacillus Calmette-Guerin

    Directory of Open Access Journals (Sweden)

    Kerigh Behzad

    2010-01-01

    Full Text Available Background and Aim: Bladder tumor is one of the most common genitourinary tumors. Management of non-muscle invasive (NMI bladder tumors is primarily by transurethral resection (TURBT followed by intravesical immunotherapy or chemotherapy. Bacillus Calmette-Guerin (BCG is the most effective adjuvant therapy in NMI bladder tumor. Since angiogenesis is an essential factor in solid tumor progression and vascular endothelial growth factor (VEGF is an important factor in angiogenesis, the aim of this study is the assessment of angiogenic factor, VEGF, serum and urine level changes in superficial bladder tumor immunotherapy by intravesical BCG. Materials and Methods: A total of 23 patients with bladder transitional cell carcinoma (TCC in stage Ta/T1 or carcinoma insitu (CIS, low or high grade, which passed a 2-4 week period from TURBT participated in this study. Blood and urine samples were obtained at first and sixth sessions before instillation of BCG. Enzyme-linked immunosorbent assay (ELISA method was used to obtain VEGF level in samples. Results: Urine and serum VEGF levels did not change significantly before and after BCG therapy. Changes in VEGF level were significantly different neither in low grade against high grade tumors nor in stage T1 against stage Ta tumors. A significant difference in VEGF level was seen between low grade and high grade tumors in serum after BCG therapy (P=0.007; but not in urine samples. Conclusion: Although intravesical BCG possesses anti-angiogenic activity, it seems that it exerts its effect through pathways other than VEGF, especially in low grade tumors.

  14. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chakiba, Camille [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Cornelis, François [Department of Radiology, Pellegrin Hospital, Bordeaux (France); Descat, Edouard [Department of Radiology, Saint-Augustin Clinic, Bordeaux (France); Gross-Goupil, Marine [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Sargos, Paul [Department of Radiotherapy, Bergonié Cancer Institute, Bordeaux (France); Roubaud, Guilhem [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Houédé, Nadine, E-mail: nadine.houede@chu-nimes.fr [Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux (France); Department of Medical Oncology, Nimes University Hosptital, Nîmes (France)

    2015-06-15

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI{sub 35s}) and venous phases (rSI{sub 80s}) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI{sub 80s} was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

  15. Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

    International Nuclear Information System (INIS)

    Highlights: • DCE-MRI parameters could be useful biomarker for patients with localized bladder carcinoma. • Rate of relapse is lower for good responders assessed by DCE-MRI. • The use of DCE-MRI parameters may improve the standardization of patients’ selection before surgery. - Abstract: Objectives: To evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. Methods: From 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI35s) and venous phases (rSI80s) of each tumour was obtained. Histological response was assessed and outcomes were recorded. Results: Histological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P = 0.03). After treatment, rSI80s was significantly different between pCR and non-pCR patients (P = 0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. Conclusion: Our results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery

  16. Clinical predictive factors of pathologic tumor response

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Chi Hwan; Kim, Won Dong; Lee, Sang Jeon; Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of)

    2012-09-15

    The aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer. The study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used. Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response. Tumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR. Pretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

  17. Does Neutrophil-to-Lymphocyte Ratio Has a Value in Predicting BCG Recurrence in Bladder Tumor Patients

    Directory of Open Access Journals (Sweden)

    Ahmet Camtosun

    2016-01-01

    Full Text Available Aim: To evaluate the prognostic value of preoperative neutrophil to lymphocyte ratio after intravesical Bacillus Calmette-Guérin (BCG treatment in non-muscle-invasive bladder cancer (NMIBC. Material and Method: The data of 70 patients, operated for urothelial carcinoma and treated with BCG after the diagnose of NMIBC at Türkiye Yüksek Ižhtisas Hastanesi between 2007-2013, were reviewed retrospectively. Patients’ preoperative complete blood counter results and first cystoscopic examination findings were recorded.Results: Median follow-up was 26 months. Tumor recurrence was identified at 26 patients (Group 2 among the 70 patients. In 44 patients there was no tumor recurrence (Group 1.  Neutrophil/lyphocyte ratio, multiplicity of tumor and cis frequency were increased statistically in Group 2 (P=0.001, P=0.005, P=0.007, respectively. Discussion: This study showed that, preoperative high neutrophil/lyphocyte ratio, multiplicity of tumor and cis precence can be used as independent criterias for predicting tumor recurrence after intravesical Bacillus Calmette-Guérin (BCG treatment in NMIBC.

  18. Experimental rat bladder urothelial cell carcinoma models

    OpenAIRE

    Arentsen, Harm C.; Hendricksen, Kees; Oosterwijk, Egbert; Witjes, J Alfred

    2009-01-01

    Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the...

  19. Small cell carcinoma of the urinary bladder

    OpenAIRE

    Terada, Tadashi

    2012-01-01

    Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positi...

  20. Invasive bladder cancer: treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation

    International Nuclear Information System (INIS)

    Purpose: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies. Methods and Materials: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor. Results: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy. Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy. Clinical 'complete responders' (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation. Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy. Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%. When these are combined, clinical complete response rates of from 65 to 80% can be achieved. Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor. Conclusions: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact. These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age. Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical

  1. [Specific types of bladder cancer].

    Science.gov (United States)

    Bertz, S; Hartmann, A; Knüchel-Clarke, R; Gaisa, N T

    2016-02-01

    Bladder cancer shows rare variants and special subtypes with diverse prognostic importance and therefore may necessitate different therapeutic approaches. For pathologists it is important to histologically diagnose and specify such variants. Nested variants of urothelial carcinoma with inconspicuous, well-formed tumor cell nests present with an aggressive course. The plasmacytoid variant, which morphologically resembles plasma cells is associated with a shorter survival time and a high frequency of peritoneal metastasis. Micropapillary urothelial carcinoma with small papillary tumor cell islands within artificial tissue retraction spaces and frequent lymphovascular invasion also has a poor prognosis. Other important rare differential variants listed in the World Health Organization (WHO) classification are microcystic, lymphoepithelioma-like, sarcomatoid, giant cell and undifferentiated urothelial carcinomas. Additionally, there are three special types of bladder cancer: squamous cell carcinoma, adenocarcinoma and small cell neuroendocrine carcinoma of the bladder. These tumors are characterized by pure squamous cell or glandular differentiation and are sometimes less responsive to adjuvant (chemo)therapy. Small cell carcinoma of the bladder mimics the neuroendocrine features of its pulmonary counterpart, shows an aggressive course but is sensitive to (neo-)adjuvant chemotherapy. The morphology and histology of the most important variants and special types are discussed in this review. PMID:26782034

  2. Determinates of tumor response to radiation: Tumor cells, tumor stroma and permanent local control

    International Nuclear Information System (INIS)

    Background and purpose: The causes of tumor response variation to radiation remain obscure, thus hampering the development of predictive assays and strategies to decrease resistance. The present study evaluates the impact of host tumor stromal elements and the in vivo environment on tumor cell kill, and relationship between tumor cell radiosensitivity and the tumor control dose. Material and methods: Five endpoints were evaluated and compared in a radiosensitive DNA double-strand break repair-defective (DNA-PKcs−/−) tumor line, and its DNA-PKcs repair competent transfected counterpart. In vitro colony formation assays were performed on in vitro cultured cells, on cells obtained directly from tumors, and on cells irradiated in situ. Permanent local control was assessed by the TCD50 assay. Vascular effects were evaluated by functional vascular density assays. Results: The fraction of repair competent and repair deficient tumor cells surviving radiation did not substantially differ whether irradiated in vitro, i.e., in the absence of host stromal elements and factors, from the fraction of cells killed following in vivo irradiation. Additionally, the altered tumor cell sensitivity resulted in a proportional change in the dose required to achieve permanent local control. The estimated number of tumor cells per tumor, their cloning efficiency and radiosensitivity, all assessed by in vitro assays, were used to predict successfully, the measured tumor control doses. Conclusion: The number of clonogens per tumor and their radiosensitivity govern the permanent local control dose

  3. Molecular detection of noninvasive and invasive bladder tumor tissues and exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes.

    Science.gov (United States)

    Sathyanarayana, Ubaradka G; Maruyama, Riichiroh; Padar, Asha; Suzuki, Makoto; Bondaruk, Jolanta; Sagalowsky, Arthur; Minna, John D; Frenkel, Eugene P; Grossman, H Barton; Czerniak, Bogdan; Gazdar, Adi F

    2004-02-15

    Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize and grow, cancer cells must invade and destroy the basement membrane. Our previous work has shown that epigenetic inactivation is a major mechanism of silencing LN5 genes in lung cancers. We extended our methylation studies to resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and voided urine; n = 71) and correlated the data with clinicopathologic findings. Nonmalignant urothelium had uniform expression of LN5 genes and lacked methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and there was excellent concordance between methylation in tumors and corresponding exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were correlated significantly with several parameters of poor prognosis (tumor grade, growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas methylation of LAMC2 and methylation index were associated with shortened patient survival. Of particular interest, methylation frequencies of LAMA3 helped to distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest that methylation of LN5 genes has potential clinical applications in bladder cancers. PMID:14973053

  4. Muscle invasive bladder cancer in Upper Egypt: the shift in risk factors and tumor characteristics

    International Nuclear Information System (INIS)

    In Egypt, where bilharziasis is endemic, bladder cancer is the commonest cancer in males and the 2nd in females; squamous cell carcinoma (SCC) is the commonest type found, with a peculiar mode of presentation. The aim of this study is to identify and rank the risk factors of muscle invasive bladder cancer (MIBC) in Upper Egypt and describe its specific criteria of presentation and histopathology. This is an analytical, hospital based, case controlled study conducted in south Egypt cancer institute through comparing MIBC cases (n = 130) with age, sex and residence matched controls (n = 260) for the presence of risk factors of MIBC. Data was collected by personal interview using a well designed questionnaire. Patients' records were reviewed for histopathology and Radiologic findings. The risk factors of MIBC were positive family history [Adjusted odds ratio (AOR) = 7.7], exposure to pesticides [AOR = 6.2], bladder stones [AOR = 5], consanguinity [AOR = 3.9], recurrent cystitis [AOR = 3.1], bilharziasis [odds ratio (OR) = 5.8] and smoking [OR = 5.3]. SCC represented 67.6% of cases with burning micturition being the presenting symptom in 73.8%. MIBC in Upper Egypt is usually of the SCC type (although its percentage is decreasing), occurs at a younger age and presents with burning micturition rather than hematuria. Unlike the common belief, positive family history, parents' consanguinity, exposure to pesticides and chronic cystitis seem to play now more important roles than bilharziasis and smoking in the development of this disease in this area

  5. Hormonal component of tumor photodynamic therapy response

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush

    2008-02-01

    The involvement of adrenal glucocorticoid hormones in the response of the treatment of solid tumors by photodynamic therapy (PDT) comes from the induction of acute phase response by this modality. This adrenal gland activity is orchestrated through the engagement of the hypothalamic-pituitary-adrenal hormonal axis incited by stress signals emanating from the PDT-treated tumor. Glucocorticoid hormone activity engendered within the context of PDT-induced acute phase response performs multiple important functions; among other involvements they beget acute phase reactant production, systemic neutrophil mobilization, and control the production of inflammation-modulating and immunoregulatory proteins.

  6. Urinary Bladder Transitional Cell Carcinogenesis Is Associated with Down-Regulation of NF1 Tumor Suppressor Gene in Vivo and in Vitro

    OpenAIRE

    Aaltonen, Vesa; Boström, Peter J.; Söderström, Karl-Ove; Hirvonen, Outi; Tuukkanen, Juha; Nurmi, Martti; Laato, Matti; Peltonen, Juha

    1999-01-01

    The NF1 gene product (neurofibromin) is known to act as a tumor suppressor protein by inactivating ras. The best documented factors involved in urinary bladder transitional cell carcinoma (TCC) are ras proto-oncogene activation and p53 suppressor gene mutations. This is the first study reporting alterations in NF1 gene expression in TCC. We examined NF1 gene expression in a total of 29 surgical urinary bladder TCC specimens representing grades 1 to 3 and in three cell lines, RT4, 5637, and T2...

  7. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    Science.gov (United States)

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented. PMID:9807870

  8. Compensatory Paracrine Mechanisms That Define The Urothelial Response to Injury in Partial Bladder Outlet Obstruction

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, James; Lendvay, Thomas S.; Sweet, Robert; Han, Chang-Hee; Soygur, Tarkan; Cheng, Jan-Fang; Plaire, J. Chadwick; Charleston, Jay S.; Charleston, Lynne B.; Bagai, Shelly; Cochrane, Kimberly; Rubio, Eric; Bassuk, James A.; Fuchs, Elaine

    2007-06-21

    Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functional protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.

  9. Impact of proteomics on bladder cancer research

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromova, Irina; Moreira, José Manuel Alfonso;

    2004-01-01

    Detecting bladder cancer at an early stage and predicting how a tumor will behave and act in response to therapy, as well as the identification of new targets for therapeutic intervention, are among the main areas of research that will benefit from the current explosion in the number of powerful ...

  10. URACHAL CARCINOMA IN BLADDER

    Institute of Scientific and Technical Information of China (English)

    薛丽燕; 吕宁; 何祖根; 林冬梅; 刘秀云

    2004-01-01

    Objective: To investigate the clinicopathologic features and diagnostic criteria of urachal carcinoma in the bladder.Methods: Seven cases of urachal carcinoma in the bladder were analyzed retrospectively. Results: All the tumors were found locating in the dome of bladder. Of them, 4 were mucinous adenocarcinoma, one was well differentiated papillary enteric adenocarcinoma, one was well differentiated squamous carcinoma, and one was neuroendocrine carcinoma. Cystomorphous urachal remnants were found in 4 cases. The main complaint was hematuria and all patients underwent partial excision of bladder and urachus. Conclusion: Mucinous adenocarcinoma is the main histo-pathological type, and cystomorphous urachal remnants are often accompanied with urachal carcinoma in the bladder. The key diagnostic criteria of urachal carcinoma in bladder are site and histopathology. And to examine the specimens carefully to find the urachal remnants is important.

  11. Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro

    Directory of Open Access Journals (Sweden)

    Wang S

    2014-08-01

    Full Text Available Shuo Wang,1 Yonghua Wang,1 Jing Liu,2 Shixiu Shao,1 Xianjun Li,1 Jiannan Gao,1 Haitao Niu,1 Xinsheng Wang1 1Department of Urology, 2Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China Objective: The aim of this study was to examine whether short hairpin RNA (shRNA expressing lentiviral particles targeting B7-H1 infection could result in B7-H1 knockdown on dendritic cells (DCs and to investigate whether B7-H1 silencing could augment the immune function of DCs and further elicit a more potent anti-tumor immune effect against bladder cancer cells in vitro. Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells, were infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1. After that, the infected DCs were pulsed by tumor antigens and used to stimulate cytotoxic T lymphocytes-based anti-tumor effect in vitro. Results: The lentivirus-mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs. Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the secretion of interleukin-12, but down-regulated interleukin-10 secretion. And more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC vaccine in vitro was also potentially augmented. Conclusion: This study suggests that a combination of B7-H1 knockdown and target antigen delivery could augment anti-tumor effects in vitro, which potentially provides a novel strategy in the immunotherapy of bladder cancer. Keywords: B7-H1, bladder cancer, dendritic cell, vaccine, immunotherapy

  12. Stepwise Application of Urine Markers to Detect Tumor Recurrence in Patients Undergoing Surveillance for Non-Muscle-Invasive Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Tilman Todenhöfer

    2014-01-01

    Full Text Available Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH, immunocytology (uCyt+, and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5% patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH showed NPVs for high-risk recurrences (G3/Cis/pT1 of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.

  13. Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer

    International Nuclear Information System (INIS)

    Bacillus Calmette Guérin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy. Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-γ ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-α and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry. Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-γ release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1

  14. Liposome-administered tetramethylhematoporphyrin (TMHP) as a photodynamic agent for bladder tumor cells

    Science.gov (United States)

    Reich, Ella D.; Bachor, Ruediger; Miller, Kurt; Koenig, Karsten; Hautmann, Richard E.

    1993-06-01

    This study was made in order to determine whether liposomes can bind and deliver the photosensitizer to human bladder carcinoma cells and how effective the photodynamic activity of this photosensitizer is. TMHP (synthesized by Prof. Muller v.d. Haegen) was incorporated into small unilamellar vesicles of DPPC, following the procedure described by Jori et al TMHP was used in a dosage of 2.5, 5, 10, and 20 (mu) g/ml on two different cell lines. Cellular uptake of TMHP in liposomes was observed by fluorescence microscopy. Dark toxicity became evident, when doses of 10 and 20 (mu) g/ml TMHP encapsulated in liposomes were compared to control liposomes without photosensitizer. PDT was performed after sensitization of cells for one hour using an argon-pumped dye laser at 630 nm and a power density of 30 mW/cm2. Irradiation with 3,6 and 7,2 Joule/cm2 resulted in a decreasing survival rate. This study demonstrates PDT-efficiency being dependent on the dose of liposome-encapsulated TMHP as well as the fluence rate. There is also a difference in cell survival according to the cell line.

  15. Alternativas Terapéuticas en las neoplasias vesicales caninas Therapeutic options in canine bladder tumors

    OpenAIRE

    R.L. Rovere; A. ALCOBA

    2002-01-01

    Las neoplasias vesicales en caninos representan menos del 1% de los tumores presentes en esta especie. El tratamiento quirúrgico se indica en tumores benignos y como complemento de la quimioterapia y radioterapia. Para la quimioterapia se emplean más frecuentemente la doxorrubicina, el 5-fluorouracilo, la ciclofosfamida, la vincristina y cisplatino. La asociación de la doxorrubicina-ciclofosfamida por vía sistémica en asociación con el cisplatino intravesical, sería un tratamiento recomendabl...

  16. HPLC assisted Raman spectroscopic studies on bladder cancer

    Science.gov (United States)

    Zha, W. L.; Cheng, Y.; Yu, W.; Zhang, X. B.; Shen, A. G.; Hu, J. M.

    2015-04-01

    We applied confocal Raman spectroscopy to investigate 12 normal bladder tissues and 30 tumor tissues, and then depicted the spectral differences between the normal and the tumor tissues and the potential canceration mechanism with the aid of the high-performance liquid chromatographic (HPLC) technique. Normal tissues were demonstrated to contain higher tryptophan, cholesterol and lipid content, while bladder tumor tissues were rich in nucleic acids, collagen and carotenoids. In particular, β-carotene, one of the major types of carotenoids, was found through HPLC analysis of the extract of bladder tissues. The statistical software SPSS was applied to classify the spectra of the two types of tissues according to their differences. The sensitivity and specificity of 96.7 and 66.7% were obtained, respectively. In addition, different layers of the bladder wall including mucosa (lumps), muscle and adipose bladder tissue were analyzed by Raman mapping technique in response to previous Raman studies of bladder tissues. All of these will play an important role as a directive tool for the future diagnosis of bladder cancer in vivo.

  17. Identifying distinct classes of bladder carcinoma using microarrays

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Andersen, Thomas Thykjær; Kruhøffer, Mogens; Jensen, Jens Ledet; Marcussen, Niels; Dutoit, Stephen Jacques Hamilton; Wolf, Hans; Ørntoft, Torben Falck

    2003-01-01

    immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis...

  18. Retinoblastoma protein expression is an independent predictor of both radiation response and survival in muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Agerbaek, M; Alsner, J; Marcussen, N;

    2003-01-01

    The objective of the study was to investigate the predictive value of various clinical, biochemical, and histopathological parameters, with special emphasis on the expression of the retinoblastoma protein (pRB), on the radiation response in bladder cancer. In order to obtain a truly objective...

  19. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

    The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

  20. Bladder Management

    Science.gov (United States)

    ... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

  1. Implication of ultrasound bladder parameters on treatment response in patients with benign prostatic hyperplasia under medical management

    Directory of Open Access Journals (Sweden)

    Rajeev Thekumpadam Puthenveetil

    2015-10-01

    Conclusion: Ultrasound bladder parameters are useful tools for measuring the treatment response in BPH patients. Our study shows that RI and DWT significantly correlate with the treatment response in BPH patients. More importantly, pretreatment values of increased IPP and PUA determines the non-improvement of symptoms in BPH patients. Our study suggests the importance of transabdominal ultrasonography (KUB–P with Doppler for evaluating treatment responses to medical management.

  2. Small cell carcinoma of the urinary bladder: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ismaili Nabil

    2009-01-01

    Full Text Available Small cell carcinoma of the bladder (SCCB is extremely rare. In this paper, we present a case of metastatic SCCB managed by chemotherapy and we would provide a brief review of the epidemiology, clinical features, diagnosis, pathologic features, staging, treatment, and prognosis of SCCB. A 52-year-old man was admitted with signs and symptoms suggestive of a bladder cancer. Computed tomography of the pelvis and abdomen showed a large tumor at the right bladder wall, measuring 10 cm in diameter, and a multinodular liver disease. Diagnosis of small cell carcinoma was established from the histological study of the transurethral resection of the bladder tumor. The patient received 12 cycles of platinum-based chemotherapy with a good partial response of bladder tumor and liver metastasis. The patient is still alive, 18 months after diagnosis.

  3. Tumor neuroectodérmico primitivo da bexiga urinária: uma rara neoplasia Primitive neuroectodermal tumor of the urinary bladder: a rare neoplasm

    Directory of Open Access Journals (Sweden)

    Daniel Cury Ogata

    2010-02-01

    Full Text Available Os autores relatam o caso de paciente do sexo feminino, 52 anos, com queixas de hematúria macroscópica e dor pélvica. Foi realizado exame ultrassonográfico, que mostrou massa expansiva em assoalho vesical. A cistoscopia confirmou a presença dessa lesão, sendo realizada biópsia. O exame histológico revelou neoplasia de pequenas células. A análise imuno-histoquímica foi necessária para elucidação diagnóstica. O referido exame demonstrou positividade para os marcadores EWS-FLI1, CD99 e S-100. O diagnóstico foi de tumor neuroectodérmico primitivo. A paciente foi tratada com quimioterapia adjuvante. Depois de sete meses de seguimento, a paciente encontra-se livre de doença.The authors report the case of a 52 year-old woman that presented macroscopic hematuria and pelvic pain. Ultrasound examination was performed, which showed an expansive mass in the bladder floor. A cystoscopy confirmed the presence of this lesion and a biopsy was carried out. Histological analysis showed a small cell neoplasm. The immunohistochemical analysis was required to establish diagnosis. This analysis revealed positivity for EWS-FLI1, CD99 and S-100. The conclusive diagnosis was primitive neuroectodermal tumor. The patient was treated with chemotherapy. After a seven month follow-up period, the patient is disease-free.

  4. Productive infection of bovine papillomavirus type 2 in the urothelial cells of naturally occurring urinary bladder tumors in cattle and water buffaloes.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available BACKGROUND: Papillomaviruses (PVs are highly epitheliotropic as they usually establish productive infections within squamous epithelia of the skin, the anogenital tract and the oral cavity. In this study, early (E and late (L protein expression of bovine papillomavirus type 2 (BPV-2 in the urothelium of the urinary bladder is described in cows and water buffaloes suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. METHODS AND FINDINGS: E5 protein, the major oncoprotein of the BPV-2, was detected in all tumors. L1 DNA was amplified by PCR, cloned and sequenced and confirmed to be L1 DNA. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection was detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the neoplastic urothelium. Finally, the early protein E2, required for viral DNA replication and known to be a pivotal factor for both productive and persistent infection, was detected by Western blot and immunohistochemically. Electron microscopic investigations detected electron dense particles, the shape and size of which are consistent with submicroscopic features of viral particles, in nuclei of neoplastic urothelium. CONCLUSION: This study shows that both active and productive infections by BPV-2 in the urothelium of the bovine and bubaline urinary bladder can occur in vivo.

  5. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

    Directory of Open Access Journals (Sweden)

    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  6. A rare case of pure small cell carcinoma of urinary bladder

    OpenAIRE

    Sunita Singh; Divya Srivastava; Hemant Yadav; Rajeev Sen

    2014-01-01

    Bladder cancer is the second most common urologic malignancy. Up to 95% of the urinary bladder tumors are of epithelial origin, from which 90% are transitional neoplasms. However, small cell carcinoma of the urinary bladder is rare tumor accounting for

  7. Inhibition of telomerase with human telomerase reverse transcriptase antisense enhances tumor necrosis factor-a-induced apoptosis in bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao-dong; CHEN Yi-rong

    2007-01-01

    Background Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells.Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity. This study investigated the effect of the telomerase inhibition with an hTERT antisense oligodeoxynucleotide (ODN) in bladder cancer cells (T24) on tumor necrosis factor-o (TNF-α)-induced apoptosis.Methods Antisense phosphorothioate oligodeoxynucleotide (AS PS-ODN) was synthesized and purified. Telomerase activity was measured by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). hTERT mRNA expression was measured by reverse transcription polymerase chain reaction (RT-PCR) assay and a gel-image system.hTERT protein was detected by immunochemistry and flow cytometry. Cell viability was measured by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium (MTT) assay. Cell apoptosis was observed by a morphological method and determined by flow cytometry.Results AS PS-ODN significantly inhibited telomerase activity and decreased the levels of hTERT mRNA which preceded the decline in the telomerase activity. AS PS-ODN significantly reduced the percentage of positive cells expressing hTERT protein following the decline of hTERT mRNA levels. There was no difference seen in the telomerase activity, hTERT mRNA expression or the protein levels between the sense phosphorothioate oligodeoxynucleotide (SPS-ODN) and the control group. AS PS-ODN treatment significantly decreased the cell viability and enhanced the apoptotic rate of T24 cells in response to TNF-α while there was no difference in cell viability and apoptotic rate between the S PS-ODN and the control group.Conclusions AS PS-ODN can significantly inhibit telomerase activity by downregulating the hTERT mRNA and protein expression. Treatment with AS PS-ODN may be a potential and most promising strategy for bladder cancer with telomerase

  8. Productive infection of bovine papillomavirus type 2 in the placenta of pregnant cows affected with urinary bladder tumors.

    Directory of Open Access Journals (Sweden)

    Sante Roperto

    Full Text Available Papillomaviruses (PVs are believed to be highly epitheliotropic as they usually establish productive infections within stratified epithelia. In vitro, various PVs appear to complete their entire life-cycle in different trophoblastic cell lines. In this study, infection by and protein expression of bovine papillomavirus type 2 (BPV-2 in the uterine and chorionic epithelium of the placenta has been described in four cows suffering from naturally occurring papillomavirus-associated urothelial bladder tumors. E5 oncoprotein was detected both by Western blot analysis and immunohistochemically. It appears to be complexed and perfectly co-localized with the activated platelet-derived growth factor ß receptor (PDGFßR by laser scanning confocal microscopy. The activated PDGFßR might be involved in organogenesis and neo-angiogenesis rather than in cell transformation during pregnancy. The major capsid protein, L1, believed to be only expressed in productive papillomavirus infection has been detected by Western blot analysis. Immunohistochemical investigations confirmed the presence of L1 protein both in the cytoplasm and nuclei of cells of the uterine and chorionic epithelium. Trophoblastic cells appear to be the major target for L1 protein expression. Finally, the early protein E2, required for viral DNA replication and known to be expressed during a productive infection, has been detected by Western blot and immunohistochemically. Electron microscopic investigations detected viral particles in nuclei of uterine and chorionic epithelium. This study shows that both active and productive infections by BPV-2 in the placenta of pregnant cows can occur in vivo.

  9. Extraskeletal myxoid chondrosarcoma: tumor response to sunitinib

    Directory of Open Access Journals (Sweden)

    Stacchiotti Silvia

    2012-10-01

    Full Text Available Abstract Background Extraskeletal myxoid chondrosarcoma (EMCS is a rare soft tissue sarcoma of uncertain differentiation, characterized in most cases by a translocation that results in the fusion protein EWSR1-CHN (the latter even called NR4A3 or TEC. EMCS is marked by >40% incidence of metastases in spite of its indolent behaviour. It is generally resistant to conventional chemotherapy, and, to the best of our knowledge, no data have been reported to date about the activity of tirosin-kinase inhibitor (TKI in this tumor. We report on two consecutive patients carrying an advanced EMCS treated with sunitinib. Methods Since July 2011, 2 patients with progressive pretreated metastatic EMCS (Patient1: woman, 58 years, PS1; Patient2: man, 63 years, PS1 have been treated with continuous SM 37.5 mg/day, on an individual use basis. Both patients are evaluable for response. In both cases diagnosis was confirmed by the presence of the typical EWSR1-CHN translocation. Results Both patients are still on treatment (11 and 8 months. Patient 1 got a RECIST response after 4 months from starting sunitinib, together with a complete response by PET. An interval progression was observed after stopping sunitinib for toxicity (abscess around previous femoral fixation, but response was restored after restarting sunitinib. Patient 2 had an initial tumor disease stabilization detected by CT scan at 3 months. Sunitinib was increased to 50 mg/day, with evidence of a dimensional response 3 months later. Conclusions Sunitinib showed antitumor activity in 2 patients with advanced EMCS. Further studies are needed to confirm these preliminary results.

  10. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  11. Interstitial cystitis/painful bladder syndrome: diagnostic evaluation and therapeutic response in a private urogynecology unit

    OpenAIRE

    Flores-Carreras, Oscar; González-Ruiz, Maria Isabel; Martínez-Espinoza, Claudia J.; Monroy-Rodríguez, Fabiola; Zaragoza-Torres, Rocio M.

    2015-01-01

    Background Interstitial cystitis/painful bladder syndrome (IC/PBS) is a spectrum of pelvic, bladder or urethral pain, as well as irritative voiding symptoms. The term interstitial cystitis (IC) is reserved for patients with typical cystoscopic features. Diagnosis and management of this syndrome may be difficult. The aim of this study was to describe endoscopic features and our experience on the treatment of this syndrome in Urodifem de Occidente S.C., a private urogynecology unit. Methods Obs...

  12. Clinical Practice Pattern of Immediate Intravesical Chemotherapy following Transurethral Resection of a Bladder Tumor in Korea: National Health Insurance Database Study.

    Science.gov (United States)

    Seo, Gi Hyeon; Kim, Jae Heon; Ku, Ja Hyeon

    2016-01-01

    We evaluated the frequency and practice pattern of immediate postoperative intravesical chemotherapy (PIC) after transurethral resection of a bladder tumor (TURBT) in suspected non-muscle-invasive bladder cancer (NMIBC). Information from the Health Insurance Review and Assessment Service database from January 1, 2008 to December 31, 2013 was used. Patients with bladder cancer who received TURBT were considered as the cases (37,941 patients and 59,568 cases). The time of PIC after TURBT, types of PIC regimens, and the potential effect of PIC on the delay for additional treatment were analyzed. The study cohort included 23,726 subjects and 30,473 cases with a mean age of 66.8 ± 12.0 years, including 19,362 (81.6%) male patients. The rate of immediate PIC was 11.0% of cases (3,359 cases). There was significant difference in the frequency rate of additional treatment among patients with immediate PIC and patients without immediate PIC within 1 year from the first TURBT (15.2% vs 16.6%, p = 0.035). However, no difference was revealed for whole observational period (33.7% vs 34.5%, p = 0.373). The frequency rate of immediate PIC after TURBT for suspected NMIBC was low in real clinical practice. More efforts are needed to improve the usage rate of PIC after TURBT for suspected NMIBC. PMID:26976048

  13. Bladder Dysfunction and Urinary Incontinence

    Directory of Open Access Journals (Sweden)

    F. faizi

    2009-01-01

    , the internal pressure of the urethra should also increase. In women, the internal pressure of the urethra is short, and even if it has poorly developed they wet themselves when they cough. "nThe causes of BD: "nAs you see there are 17 causes, which 11 are related to the bladder. The bladder is responsible for retaining the urine and voiding. "nPathophysiology: "nThe bladder and sphincter should work in a coordinated manner: "nDuring the course of a day, an average person will void approximately 4-8 times. The urinary bladder is in storage mode for most of the day, allowing an individual to engage in more important activities than urination. "nNormal bladder function consists of 2 phases—filling and emptying. The normal micturition cycle requires the urinary bladder and the urethral sphincter working together as a coordinated unit to store and empty urine. During urinary storage, the bladder acts as a low-pressure receptacle, while the urinary sphincter maintains high resistance to urinary flow to keep the bladder outlet closed. During urine elimination, the bladder contracts to expel urine while the urinary sphincter opens (low resistance to allow unobstructed urinary flow and bladder emptying. "nFilling phase: "nDuring the filling phase, the bladder accumulates increasing volumes of urine while the pressure inside the bladder remains low. The pressure within the bladder must be lower than the urethral pressure during the filling phase. If the bladder pressure is greater than the urethral pressure (resistance, urine will leak out. "nThe filling of the urinary bladder depends on the intrinsic viscoelastic properties of the bladder and the inhibition of the parasympathetic nerves. Thus, bladder filling is primarily a passive event. "nSympathetic nerves also facilitate urine storage in the following ways: "nSympathetic nerves inhibit the parasympathetic nerves from triggering bladder contractions. "nSympathetic nerves directly cause relaxation and expansion of the

  14. Molecular networks discriminating mouse bladder responses to intravesical bacillus Calmette-Guerin (BCG, LPS, and TNF-α

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2008-02-01

    development of the lymphatic system. Interestingly, TNF-α-specific networks overlapped with the following canonical signaling pathways: PPAR, death receptor, and apoptosis. Finally, LPS-specific networks overlapped with the LPS/IL-1 mediated inhibition of RXR. Because NF-kappaB occupied a central position in several networks, we further determined whether this transcription factor was part of the responses to BCG. Electrophoretic mobility shift assays confirmed the participation of NF-kappaB in the mouse bladder responses to BCG. In addition, BCG treatment of a human urothelial cancer cell line (J82 also increased the binding activity of NF-kappaB, as determined by precipitation of the chromatin by a NF-kappaB-p65 antibody and Q-PCR of genes bearing a NF-kappaB consensus sequence. Next, we tested the hypothesis of whether small GTPases such as LRG-47 are involved in the uptake of BCG by the bladder urothelium. Conclusion As expected, BCG treatment induces the transcription of genes belonging to common pro-inflammatory networks. However, BCG also induces unique genes belonging to molecular networks involved in axonal guidance and lymphatic system development within the bladder target organ. In addition, NF-kappaB seems to play a predominant role in the bladder responses to BCG therapy. Finally, in intact urothelium, BCG-GFP internalizes in LRG-47-positive vesicles. These results provide a molecular framework for the further study of the involvement of immune and nervous systems in the bladder responses to BCG therapy.

  15. Tumor suppressor p53 response is blunted

    International Nuclear Information System (INIS)

    The biological effect of low-dose radiation has been a focus of research interest in recent years because this area has important implications for radiation protection at doses of 0-1 Gy. At present, there is a lack of substantial evidence to indicate harmful effects of these low doses, in contrast, epidemiological data regarding the cancer incidence from areas with high background radiation levels seem to favor a beneficial effect of chronic low-dose radiation. To strengthen these aspects of radiation science, more molecular evidence on the cellular response to low doses is required. In the field of tumor biology, p53 may be one of the best studied molecules. Besides its function as a potent tumor suppressor, p53 is also found to govern G1 and/or G2/M checkpoint response in cells under stressful conditions. One of the mediators of p53 is waf1, an inhibitor of cyclin-dependent kinase. By inducing cell cycle arrest or apoptosis and probably DNA repair, activation of the p53-dependent signal transduction pathway minimizes the inheritance of damaged genetic information thereby maintaining genomic stability. Recently, we and other investigators found that the agents that evoke the p53 pathway are not limited to DNA-damaging agents but also include non-DNA-damaging stressors. Therefore, p53 may also be viewed as a major player in maintaining cellular homeostasis. Acute low dose irradiation (0.1-1 Gy, 1.33 Gy/min) of a human glioblastoma cell line, A-172 (wp53) induced a dose-dependent monophasic accumulation of p53 and wild-type p53 activated factor-1, WAF1. Different from this, chronic γ-irradiation (0.001 Gy/min) produced a clear biphasic response of p53 accumulation with the first peak at 1.5 h (0.09 Gy) and the second peak at 10 h (0.54 Gy). Significantly when the cells were pre-irradiated with chronic γ-irradiation for 24 h (1.44 Gy) or 50 h (3 Gy), they could no longer response to the second acute challenging irradiation to produce a dose-dependent response of

  16. Bladder Retraining

    Science.gov (United States)

    ... a better voiding pattern around the clock. Do Kegel Exercises Help People with IC? Some bladder retraining programs recommend practicing Kegel exercises as part of bladder retraining. Kegel exercises ...

  17. Urinary Bladder

    Science.gov (United States)

    ... to the symphysis pubis, and below the parietal peritoneum . The size and shape of the urinary bladder ... outer layer of the bladder wall is parietal peritoneum. In all other regions, the outer layer is ...

  18. Bladder Health

    Science.gov (United States)

    ... life (the person’s level of health, comfort, and happiness). In fact, people with bladder problems may have a lower quality of life than people with diabetes, heart disease, or high blood pressure. Bladder problems ...

  19. Differences of response of human bladder cancer cells to photodynamic therapy (PDT) with Hypericum perforantum L extract and Photofrin

    Science.gov (United States)

    Nseyo, Unyime; Kim, Albert; Stavropoulos, Nikos E.; Skalkos, Dimitris; Nseyo, Unwana U.; Chung, Theodore D.

    2005-04-01

    Refractory carcinoma in situ and resistant multifocal transitional cell carcinoma (TCC) of the human urinary bladder respond modestly to PHOTOFRIN (PII) PDT. Hypericum perforatum L., (St. John"s wort /Epirus" Vasalmo, Greece), a medicinal plant used for many human ailments, is under investigation as a new photosensitizer. We have reported on the antiproliferative activity of the lipophilic extract of the Hypericum perforatum L. (HP) against cultured T-24, and NBT-11 bladder cancer cells. We investigated response of the polar methanolic fraction (PMF) of the HP extract versus PHOTOFRIN in photodynamic therapy (PDT) of human bladder cancer cells, RT-4 and T-24.The PMF was extracted from the dry herb with methanol, followed by liquid extraction with petroleum ether. RT-4/T-24, were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PII 2ug/ml, or PMF 60ug /ml was added and incubation continued. After 24 hours, the cells were treated with laser light (630nm) with 0,1,2,4 and 8 Joules. The cells were then washed and reincubated for another 24 hours. After this incubation cell survival was assessed by the MTT assay. PMF-PDT induced percent cell kill of 0%, 0%, 0%, 29% and 75%, in RT-4 cells (primary noninvasive urinary bladder TCC) versus 5%, 9%, 13%, 69% and 86%, in T-24 cells(metastatic TTC) at 0,1,2,4 and 8 Joules respectively. PII-PDT induced cell kill of 0 %, 0% ,0%,0% and 9 %, in RT-4 cells versus 0%,10%,0%,21% and 77%, in T-24 cells at 0,1,2,4 and 8 Joules respectively.RT-24 cells were relatively more resistant than T-24 cells to PMF and PII-PDT. Understanding mechanisms of such differential responses might prove useful

  20. 闭孔神经与膀胱肿瘤基底部联合阻滞在经尿道膀胱肿瘤电切术中的应用%The Application of Combined Blockade of Obturator Nerve and Basilar Part of Bladder Tumor in Transurethral Electroresection of Bladder Tumor

    Institute of Scientific and Technical Information of China (English)

    李颖波; 余开峰; 冉然

    2012-01-01

    Objective To investigate the combined blockade of the feasibility of obturator nerve and basilar part of bladder tumor in preventing obturator nervous reflex during transurethral electroresection of bladder tumor (TURBT). Methods Seventy - two patients with bladder tumor close to the ureter,suffered from TURBT under combined spinal epidural anesthesia, were randomly divided into two group: N group ( n = 36) and P group (n = 36). Before TURBT, obturator nerve blockade under guidance of nerve stimulator were performed in N group. Obturator nerve and basilar part of bladder tumor combined blockade were performed in P group. Results In N group,seven patients (7/36, 19% ) showed obturator nervous reflex during TURBT, five patients showed slight obturator nervous reflex, two patients showed apparent nervous reflex. In P group,only three patients (3/36,8% ) showed slight obturator nervous reflex during TURBT without vesical perforation. Compared with N group, there had a significant difference (P<0.05). Conclusion In TURBT,the combined blockade of obturator nerve and basilar part of bladder tumor could inhibit the obturator nerve reflex and decrease the incidence of operative complications.%目的:探讨闭孔神经与膀胱肿瘤基底部联合阻滞在经尿道膀胱肿瘤电切术(TURBT)中预防闭孔神经反射的可行性.方法:72例膀胱肿瘤位于输尿管附近拟行经尿道膀胱肿瘤电切术患者,均在腰-硬联合麻醉下行TURBT,单阻滞组在神经刺激器指导下行闭孔神经阻滞,联合阻滞组行闭孔神经与膀胱肿瘤基底部联合阻滞,再行膀胱肿瘤电切.结果:单阻滞组有7例(19%)出现闭孔神经反射,5例轻微,2例严重;联合阻滞组仅有3例(8%)出现轻微的闭孔神经反射,无膀胱穿孔(P<0.05).结论:经尿道膀胱肿瘤电切术闭孔神经与膀胱肿瘤基底部联合阻滞能有效抑制闭孔神经反射,减少手术并发症.

  1. Whole-Pelvis or Bladder-Only Chemoradiation for Lymph Node–Negative Invasive Bladder Cancer: Single-Institution Experience

    International Nuclear Information System (INIS)

    Purpose: Whole-pelvis (WP) concurrent chemoradiation (CCRT) is the standard bladder preserving option for patients with invasive bladder cancer. The standard practice is to treat elective pelvic lymph nodes, so our aim was to evaluate whether bladder-only (BO) CCRT leads to results similar to those obtained by standard WP-CCRT. Methods and Materials: Patient eligibility included histopathologically proven muscle-invasive bladder cancer, lymph nodes negative (T2–T4, N−) by radiology, and maximal transurethral resection of bladder tumor with normal hematologic, renal, and liver functions. Between March 2005 and May 2006, 230 patients were accrued. Patients were randomly assigned to WP-CCRT (120 patients) and BO-CCRT (110 patients). Data regarding the toxicity profile, compliance, initial complete response rates at 3 months, and occurrence of locoregional or distant failure were recorded. Results: With a median follow-up time of 5 years (range, 3–6), WP-CCRT was associated with a 5-year disease-free survival of 47.1% compared with 46.9% in patients treated with BO-CCRT (p = 0.5). The bladder preservation rates were 58.9% and 57.1% in WP-CCRT and BO-CCRT, respectively (p = 0.8), and the 5-year overall survival rates were 52.9% for WP-CCRT and 51% for BO-CCRT (p = 0.8). Conclusion: BO-CCRT showed similar rates of bladder preservation, disease-free survival, and overall survival rates as those of WP-CCRT. Smaller field sizes including bladder with 2-cm margins can be used as bladder preservation protocol for patients with muscle-invasive lymph node–negative bladder cancer to minimize the side effects of CCRT.

  2. Role of the chronic bacterial infection in urinary bladder carcinogenesis

    International Nuclear Information System (INIS)

    The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection.3H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis

  3. The comparative effects of aminoglycoside antibiotics and muscle relaxants on electrical field stimulation response in rat bladder smooth muscle.

    Science.gov (United States)

    Min, Chang Ho; Min, Young Sil; Lee, Sang Joon; Sohn, Uy Dong

    2016-06-01

    It has been reported that several aminoglycoside antibiotics have a potential of prolonging the action of non-depolarizing muscle relaxants by drug interactions acting pre-synaptically to inhibit acetylcholine release, but antibiotics itself also have a strong effect on relaxing the smooth muscle. In this study, four antibiotics of aminoglycosides such as gentamicin, streptomycin, kanamycin and neomycin were compared with skeletal muscle relaxants baclofen, tubocurarine, pancuronium and succinylcholine, and a smooth muscle relaxant, papaverine. The muscle strips isolated from the rat bladder were stimulated with pulse trains of 40 V in amplitude and 10 s in duration, with pulse duration of 1 ms at the frequency of 1-8 Hz, at 1, 2, 4, 6, 8 Hz respectively. To test the effect of four antibiotics on bladder smooth muscle relaxation, each of them was treated cumulatively from 1 μM to 0.1 mM with an interval of 5 min. Among the four antibiotics, gentamicin and neomycin inhibited the EFS response. The skeletal muscle relaxants (baclofen, tubocurarine, pancuronium and succinylcholine) and inhibitory neurotransmitters (GABA and glycine) did not show any significant effect. However, papaverine, had a significant effect in the relaxation of the smooth muscle. It was suggested that the aminoglycoside antibiotics have inhibitory effect on the bladder smooth muscle. PMID:27260628

  4. Holmium: yttrium-aluminum-garnet (Ho:YAG laser for resection of bladder tumor in a pediatric patient

    Directory of Open Access Journals (Sweden)

    Suleyman Cakmakci

    2015-09-01

    Full Text Available Bladder tumours are rare in children, with only 0.4% of cases occurring in the first 2 decades of life. Herein, a pediatric patient who underwent TUR-B with a holmium: yttrium-aluminum-garnet (Ho:YAG laser is presented. Its histopathology was reported as urothelial papilloma.

  5. Genetics Home Reference: bladder cancer

    Science.gov (United States)

    ... ND, Rubenstein JN, Eggener SE, Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol. 2003 Apr;169(4):1219-28. ...

  6. Small Cell Carcinoma of the Bladder

    OpenAIRE

    Çiçek, Tufan; Coşkunoğlu, Esra Zeynep; Duran, Berkan; Çiftci, Egemen

    2015-01-01

    Small Cell Carcinoma of the bladder accounts for less than 1% of all bladder tumors. Small Cell Carcinoma of the bladder has an aggressive behaviour and is usually metastatic at diagnosis. Due to its infrequent occurence, the literature on this entity is limited; which unsurprisingly leads to an uncertanity in defining an ideal therapeutic approach. This report, overviews the literature while describing a 70- year- old female patient who is diagnosed with small cell carcinoma of the bladder a...

  7. Small Cell Carcinoma of the Bladder

    OpenAIRE

    Tufan Cicek; Esra Zeynep Coskunoglu; Berkan Duran; Egemen Ciftci

    2015-01-01

    Small Cell Carcinoma of the bladder accounts for less than 1% of all bladder tumors. Small Cell Carcinoma of the bladder has an aggressive behaviour and is usually metastatic at diagnosis. Due to its infrequent occurence, the literature on this entity is limited; which unsurprisingly leads to an uncertanity in defining an ideal therapeutic approach. This report, overviews the literature while describing a 70- year- old female patient who is diagnosed with small cell carcinoma of the bladder ...

  8. Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen

    Directory of Open Access Journals (Sweden)

    Weiren Huang

    2015-01-01

    Full Text Available Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1 were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

  9. Mucinous Bladder Adenocarcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Bruno Mello R. Santos

    2015-01-01

    Full Text Available Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer, with aggressive behavior and poor response to chemotherapy and radiotherapy. The symptoms are similar to those of other bladder tumors. Surgery is the main treatment and remains the only curative option. There may be a progression from mucinous metaplasia to mucinous adenoma and then mucinous adenocarcinoma. We present the case of a 40-year-old woman with recurrent lower urinary tract infections, submitted to imaging tests, which showed a bladder tumor. After transurethral resection, pathology showed intestinal mucinous carcinoma. Metastatic work-up was negative. New surgical procedure showed metaplasia but no recurrence of the carcinoma. The patient is now using antibiotic prophylaxis and will undergo a cystoscopy every 3 months and computed tomography in one year.

  10. 30. Knockdown of IGF-IR by Antisense Oligodeoxynucleotide auguments the sensitivity of bladder cancer cells to MMC

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AND AIM: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50-to 70- year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection. So drug resistance, especially in its multiple type forms, remains a major and difficult problem to resolve in bladder cancer therapy. This phenomenon has often been ascribed to strictly pharmacolo-gic factors, such as the overexpression of multidrug transporters P-glycoprotein, multidrug resistance related protein (MRP), and other variables closely implicated DNA repair and induction/modulation of apoptosis, such as P53 and the Bcl-protein family. Furthermore, it has been recently shown that certain growth factors(IGFs etc) may be involved in the mechanism of drug resistance. Clearly, these findings suggest the design of new strategies that might improve bladder tumor response to chemotherapy. Results have previously shown that human bladder tumor cell lines may be adapted to grow in the complete absence of serum or any other growth supplement and that this can be explained on the basis of autocrine stimulation. The acquirement of autonomous growth capacity was likely to be an important element in the oncogenesis of bladder tumors. Furthermore, criss-cross experiments showed that supernatants stimulated not only proliferation of the autologous cell line of bladder cancer, but also growth of the other bladder cancer cell lines, suggesting the production of common autocrine factors in bladder tumor cells. Some factors or their receptors involved in autocrine loop mechanism of bladder tumor cells have been confirmed, such as IL-6, the epidermal growth factor receptor, IFN-beta, transferrins-like substance etc. But certain factors which may

  11. Inhibition of macrophage migration inhibitory factor decreases proliferation and cytokine expression in bladder cancer cells

    International Nuclear Information System (INIS)

    The importance of various inflammatory cytokines in maintaining tumor cell growth and viability is well established. Increased expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) has previously been associated with various types of adenocarcinoma. MIF IHC was used to localize MIF in human bladder tissue. ELISA and Western blot analysis determined the synthesis and secretion of MIF by human bladder transitional cell carcinoma cells. The effects of MIF inhibitors (high molecular weight hyaluronate (HA), anti-MIF antibody or MIF anti-sense) on cell growth and cytokine expression were analyzed. Human bladder cancer cells (HT-1376) secrete detectable amounts of MIF protein. Treatment with HA, anti-MIF antibody and MIF anti-sense reduced HT-1376 cell proliferation, MIF protein secretion, MIF gene expression and secreted inflammatory cytokines. Our evidence suggests MIF interacts with the invariant chain, CD74 and the major cell surface receptor for HA, CD44. This study is the first to report MIF expression in the human bladder and these findings support a role for MIF in tumor cell proliferation. Since MIF participates in the inflammatory response and bladder cancer is associated with chronic inflammatory conditions, these new findings suggest that neutralizing bladder tumor MIF may serve as a novel therapeutic treatment for bladder carcinoma

  12. Interleukin 2 expression by tumor cells alters both the immune response and the tumor microenvironment.

    Science.gov (United States)

    Lee, J; Fenton, B M; Koch, C J; Frelinger, J G; Lord, E M

    1998-04-01

    Microenvironmental conditions within solid tumors can have marked effects on the growth of the tumors and their response to therapies. The disorganized growth of tumors and their attendant vascular systems tends to result in areas of the tumors that are deficient in oxygen (hypoxic). Cells within these hypoxic areas are more resistant to conventional therapies such as radiation and chemotherapy. Here, we examine the hypoxic state of EMT6 mouse mammary tumors and the location of host cells within the different areas of the tumors to determine whether such microenvironmental conditions might also affect their ability to be recognized by the immune system. Hypoxia within tumors was quantified by flow cytometry and visualized by immunohistochemistry using a monoclonal antibody (ELK3-51) against cellular adducts of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetam ide (EF5), a nitroimidazole compound that binds selectively to hypoxic cells. Thy-1+ cells, quantified using a monoclonal antibody, were found only in the well-oxygenated areas. The location of these Thy-1+ cells was also examined in EMT6 tumors that had been transfected with the gene for interleukin-2 (IL-2) because these tumors contain greatly increased numbers of host cells. Surprisingly, we found that IL-2-transfected tumors had significantly decreased hypoxia compared to parental tumors. Furthermore, using the fluorescent dye Hoechst 33342, an in vivo marker of perfused vessels, combined with immunochemical staining of PECAM-1 (CD31) as a marker of tumor vasculature, we found increased vascularization in the IL-2-transfected tumors. Thus, expression of IL-2 at the site of tumor growth may enhance tumor immunity not only by inducing the generation of tumor-reactive CTLs but also by allowing increased infiltration of activated T cells into the tumors. PMID:9537251

  13. Neurogenic Bladder

    Directory of Open Access Journals (Sweden)

    Peter T. Dorsher

    2012-01-01

    Full Text Available Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented.

  14. Suppression of T cell responses in the tumor microenvironment.

    Science.gov (United States)

    Frey, Alan B

    2015-12-16

    The immune system recognizes protein antigens expressed in transformed cells evidenced by accumulation of antigen-specific T cells in tumor and tumor draining lymph nodes. However, despite demonstrable immune response, cancers grow progressively suggesting that priming of antitumor immunity is insufficiently vigorous or that antitumor immunity is suppressed, or both. Compared to virus infection, antitumor T cells are low abundance that likely contributes to tumor escape and enhancement of priming is a long-sought goal of experimental vaccination therapy. Furthermore, patient treatment with antigen-specific T cells can in some cases overcome deficient priming and cause tumor regression supporting the notion that low numbers of T cells permits tumor outgrowth. However, tumor-induced suppression of antitumor immune response is now recognized as a significant factor contributing to cancer growth and reversal of the inhibitory influences within the tumor microenvironment is a major research objective. Multiple cell types and factors can inhibit T cell functions in tumors and may be grouped in two general classes: T cell intrinsic and T cell extrinsic. T cell intrinsic factors are exemplified by T cell expression of cell surface inhibitory signaling receptors that, after contact with cells expressing a cognate ligand, inactivate proximal T Cell Receptor-mediated signal transduction therein rendering T cells dysfunctional. T cell extrinsic factors are more diverse in nature and are produced by tumors and various non-tumor cells in the tumor microenvironment. These include proteins secreted by tumor or stromal cells, highly reactive soluble oxygen and nitrogen species, cytokines, chemokines, gangliosides, and toxic metabolites. These factors may restrict T cell entrance into the tumor parenchyma, cause inactivation of effector phase T cell functions, or induce T cell apoptosis ultimately causing diminished cancer elimination. Here, we review the contributions of inhibitory

  15. SOX4 expression in bladder carcinoma

    DEFF Research Database (Denmark)

    Aaboe, Mads; Birkenkamp-Demtroder, Karin; Wiuf, Carsten;

    2006-01-01

    The human transcription factor SOX4 was 5-fold up-regulated in bladder tumors compared with normal tissue based on whole-genome expression profiling of 166 clinical bladder tumor samples and 27 normal urothelium samples. Using a SOX4-specific antibody, we found that the cancer cells expressed the...

  16. Combined effect of tumor necrosis factor-alpha and ionizing radiation on the induction of apoptosis in 5637 bladder carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Baierlein, S.A.; Distel, L.; Sieber, R.; Weiss, C.; Roedel, C.; Sauer, R.; Roedel, F. [Dept. of Radiation Oncology, Friedrich Alexander Univ. Erlangen-Nuremberg (Germany)

    2006-08-15

    Background and Purpose: Apoptosis can be induced by distinct but overlapping pathways. Ionizing radiation induces apoptosis by an ''intrinsic'', mitochondria-dependent pathway. Ligation of tumor necrosis factor-(TNF-){alpha}, FAS (CD95) or TRAIL receptors are typical representatives of an extrinsic, death-receptor-mediated pathway. In this study the effect of irradiation, treatment with the cytokine TNF-{alpha}, or a combination of both on the induction of apoptosis and clonogenic survival of bladder carcinoma cells was investigated. Material and Methods: 5637 bladder carcinoma cells were treated with different concentrations of recombinant TNF-{alpha} (0-10 ng/ml), irradiated with single doses ranging from 0.5 to 10 Gy, or a combination of both modalities. Apoptotic cells were quantified by the TUNEL assay up to 96 h following treatment, clonogenic cell survival by a clonogenic assay. Synergistic effects of both modalities were evaluated using isobolographic analysis. Results: Irradiation of 5637 carcinoma cells resulted in a discontinuous dose dependence of the apoptotic fraction with a pronounced increase in the range of 0-2 Gy and a slighter increase at 2-10 Gy. The percentage of apoptotic carcinoma cells also increased continuously after treatment with lower concentrations of TNF-{alpha} reaching a plateau at concentrations of 5.0-10.0 ng/ml. Isobolographic analysis revealed a supraadditive interrelationship between irradiation and TNF-{alpha} in the range between 0.005 and 0.5 ng/ml, and an additive effect for TNF-{alpha} concentrations > 0.5 ng/ml. The additive effects were confirmed in clonogenic survival assays with reduced survival fractions following combined TNF-{alpha} administration and irradiation. Conclusion: The combination of two apoptosis-inducing modalities resulted in a synergistic effect on the induction of apoptosis in 5637 bladder carcinoma cells. Although a radiosensitizing effect still has to be proven in animal models

  17. Contemporary management of low-risk bladder cancer

    NARCIS (Netherlands)

    Falke, J.; Witjes, J.A.

    2011-01-01

    Bladder cancer comprises a heterogeneous group of tumors, the majority of which are non-muscle-invasive bladder cancer (NMIBC) at initial presentation. Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome. Although the ris

  18. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

    DEFF Research Database (Denmark)

    Ostenfeld, Marie Stampe; Bramsen, Jesper Bertram; Lamy, Philippe;

    2010-01-01

    Downregulation of miR-145 in a variety of cancers suggests a possible tumor suppressor function for this microRNA. Here, we show that miR-145 expression is reduced in bladder cancer and urothelial carcinoma in situ, compared with normal urothelium, using transcription profiling and in situ...... hybridization. Ectopic expression of miR-145 induced extensive apoptosis in urothelial carcinoma cell lines (T24 and SW780) as characterized by caspase activation, nuclear condensation and fragmentation, cellular shrinkage, and detachment. However, cell death also proceeded upon caspase inhibition by the...... pharmacological inhibitor zVAD-fmk and ectopic expression of anti-apoptotic Bcl-2, indicating the activation of an alternative caspase-independent death pathway. Microarray analysis of transcript levels in T24 cells, before the onset of cell death, showed destabilization of mRNAs enriched for miR-145 7mer target...

  19. Microvesicles derived from human umbilical cord Wharton's jelly mesenchymal stem cells attenuate bladder tumor cell growth in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Shuai Wu

    Full Text Available Several studies suggest that mesenchymal stem cells (MSCs possess antitumor properties; however, the exact mechanisms remain unclear. Recently, microvesicles (MVs are considered as a novel avenue intercellular communication, which may be a mediator in MSCs-related antitumor effect. In the present study, we evaluated whether MVs derived from human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs may inhibit bladder tumor T24 cells growth using cell culture and the BALB/c nu/nu mice xenograft model. CCK-8 assay and Ki-67 immunostaining were performed to estimate cell proliferation in vitro and in vivo. Flow cytometry and TUNEL assay were used to assess cell cycle and apoptosis. To study the conceivable mechanism by which hWJMSC-MVs attenuate bladder tumor T24 cells, we estimated the expression of Akt/p-Akt, p-p53, p21 and cleaved Caspase 3 by Western blot technique after exposing T24 cells to hWJMSC-MVs for 24, 48 and 72h. Our data indicated that hWJMSC-MVs can inhibit T24 cells proliferative viability via cell cycle arrest and induce apoptosis in T24 cells in vitro and in vivo. This study showed that hWJMSC-MVs down-regulated phosphorylation of Akt protein kinase and up-regulated cleaved Caspase 3 during the process of anti-proliferation and pro-apoptosis in T24 cells. These results demonstrate that hWJMSC-MVs play a vital role in hWJMSC-induced antitumor effect and may be a novel tool for cancer therapy as a new mechanism of cell-to-cell communication.

  20. Enhanced Control of Bladder-Associated Tumors Using Shrimp Anti-Lipopolysaccharide Factor (SALF Antimicrobial Peptide as a Cancer Vaccine Adjuvant in Mice

    Directory of Open Access Journals (Sweden)

    Han-Ning Huang

    2015-05-01

    Full Text Available Shrimp anti-lipopolysaccharide factor (SALF is an antimicrobial peptide with reported anticancer activities, such as suppression of tumor progression. In this study, we prepared a potential cancer vaccine comprised of SALF in conjunction with the cell lysate of inactivated murine bladder carcinoma cells (MBT-2, and evaluated its efficacy in a mouse tumor model. Our study shows that SALF added to cell culture media inhibits growth progression of MBT-2, and that SALF together with inactivated MBT-2 lysate elevates the level of inflammasome activity, and modulates the levels of IL-1β, MCP-1, IL-6, IL-12, and TNF-α in mouse macrophages. Immunization of 7, 14, and 21 day-old mice with the vaccine prevented growth of MBT-2 cell-mediated tumors. The vaccine was found to enhance expression of T-cell, cytotoxic T cells, and NK cells in the immunized mice groups. Recruitment of macrophages, T-helper cells, and NK cells was enhanced, but levels of VEGF were decreased in immunized mice. This report provides empirical evidence that our SALF as vaccine adjuvant enhances antitumor immunity in mice.

  1. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Rim Hojeij

    2016-07-01

    Full Text Available Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC and it is amenable to local treatments, with intravesical (IVES Bacillus-Calmette-Guerin (BCG immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK combined to Ganciclovir (GCV led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC.

  2. Immunogenic Human Papillomavirus Pseudovirus-Mediated Suicide-Gene Therapy for Bladder Cancer.

    Science.gov (United States)

    Hojeij, Rim; Domingos-Pereira, Sonia; Nkosi, Marianne; Gharbi, Dalila; Derré, Laurent; Schiller, John T; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2016-01-01

    Bladder cancer is the second most common urological malignancy in the world. In 70% of cases it is initially diagnosed as non-muscle-invasive bladder cancer (NMIBC) and it is amenable to local treatments, with intravesical (IVES) Bacillus-Calmette-Guerin (BCG) immunotherapy being routinely used after transurethral resection of the lesion. However, this treatment is associated with significant side-effects and treatment failures, highlighting the necessity of novel strategies. One potent approach is the suicide-gene mediated therapy/prodrug combination, provided tumor-specificity can be ensured and anti-tumor immune responses induced. Using the mouse syngeneic orthotopic MB49-bladder tumor model, here we show that IVES human papillomavirus non-replicative pseudovirions (PsV) can pseudoinfect tumors with a ten-fold higher efficacy than normal bladders. In addition, PsV carrying the suicide-gene herpes-simplex virus thymidine kinase (PsV-TK) combined to Ganciclovir (GCV) led to immunogenic cell-death of tumor cells in vitro and to MB49-specific CD8 T-cells in vivo. This was associated with reduction in bladder-tumor growth and increased mice survival. Altogether, our data show that IVES PsV-TK/GCV may be a promising alternative or combinatory treatment for NMIBC. PMID:27428950

  3. Effect of Allicin in Antagonizing Mice's Bladder Cancer in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    王坚; 何惠娟; 何承伟; 吴平; 柳建军

    2004-01-01

    Objective: To explore anti-tumor effect and mechanism of Allicin in treating murine bladder tumor. Methods: To observe Allicin's effect on MBT-2 tumor cells in vitro, 100 μg/ml Allicin was added to the tumor cell culture, and the morphology of tumor cells was observed by phase contrast microscope 6 hrs later.The direct effects of Allicin on tumor cell growth in vitro in the MTT Assay was also evaluated. To determine anti-tumor effect of Allicin in vivo, C3H/He mice were randomly grouped prior to initiation of experiment. The mice received 1 × 105 MBT-2 cells administered subcutaneously into the right posterior flank on the Day 0 the experiment started. Allicin was injected at the site near tumor transplantation on the Day 1. The mice were examined for tumor development and the tumors were measured in two dimensions with calipers twice a week. On Day 21 the tumors were resected and examined pathologically to see the immune response. Results: The observation of morphology of MBT-2 cells in vitro and MTT assay indicated that Allicin has apparent direct cytotoxicity to bladder cancer cells. In high dosage group, a marked delay was shown in the appearance and growth of tumors after subcutaneously injection when compared with the control group (P<0.01). Histology studies suggested that there were more macrophages, lymphocytes and fibroblasts at the peri-tumor region than the control group. Conclusion: Allicin has a marked tumor inhibitory effect on bladder tumor. This effect could possibly be related to direct cytotoxicity and activation of immune response. It could as possibly prove to be an effective intravesical treatment agent for superficial bladder cancer.

  4. Action of tetrodotoxin on the contractile responses of isolated guinea-pig urinary bladder preparation to X-irradiation and to electrical stimulation

    International Nuclear Information System (INIS)

    Tetrodotoxin (10-8 to 10-6 g/ml) blocked the contractile responses of isolated guinea-pig urinary bladder preparation to electrical (25 and 100 Hz) neural but not to transmural stimulation and to X-irradiation (50 kV, 20 kR/min, 20 kR). The irradiation had no influence on the bladder responses to electrical and hormonal (acetylcholine and histamine) stimulation. It is concluded that the X-ray-induced contraction is of myogenic origin and that it is possibly not related to the electro-mechanical coupling system. (orig.)

  5. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  6. Lymphatic vessel density and function in experimental bladder cancer

    International Nuclear Information System (INIS)

    The lymphatics form a second circulatory system that drains the extracellular fluid and proteins from the tumor microenvironment, and provides an exclusive environment in which immune cells interact and respond to foreign antigen. Both cancer and inflammation are known to induce lymphangiogenesis. However, little is known about bladder lymphatic vessels and their involvement in cancer formation and progression. A double transgenic mouse model was generated by crossing a bladder cancer-induced transgenic, in which SV40 large T antigen was under the control of uroplakin II promoter, with another transgenic mouse harboring a lacZ reporter gene under the control of an NF-κB-responsive promoter (κB-lacZ) exhibiting constitutive activity of β-galactosidase in lymphatic endothelial cells. In this new mouse model (SV40-lacZ), we examined the lymphatic vessel density (LVD) and function (LVF) during bladder cancer progression. LVD was performed in bladder whole mounts and cross-sections by fluorescent immunohistochemistry (IHC) using LYVE-1 antibody. LVF was assessed by real-time in vivo imaging techniques using a contrast agent (biotin-BSA-Gd-DTPA-Cy5.5; Gd-Cy5.5) suitable for both magnetic resonance imaging (MRI) and near infrared fluorescence (NIRF). In addition, IHC of Cy5.5 was used for time-course analysis of co-localization of Gd-Cy5.5 with LYVE-1-positive lymphatics and CD31-positive blood vessels. SV40-lacZ mice develop bladder cancer and permitted visualization of lymphatics. A significant increase in LVD was found concomitantly with bladder cancer progression. Double labeling of the bladder cross-sections with LYVE-1 and Ki-67 antibodies indicated cancer-induced lymphangiogenesis. MRI detected mouse bladder cancer, as early as 4 months, and permitted to follow tumor sizes during cancer progression. Using Gd-Cy5.5 as a contrast agent for MRI-guided lymphangiography, we determined a possible reduction of lymphatic flow within the tumoral area. In addition, NIRF

  7. Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

    Directory of Open Access Journals (Sweden)

    Dozmorov Igor

    2007-05-01

    Full Text Available Abstract Background Tachykinins (TK, such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs. Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2. In the absence of

  8. Motor response of the human isolated small intestine and urinary bladder to porcine neuromedin U-8.

    OpenAIRE

    Maggi, C. A.; Patacchini, R.; S. Giuliani; Turini, D; Barbanti, G.; ROVERO P; Meli, A.

    1990-01-01

    1. Porcine neuromedin U-8 produced a concentration (0.3 nM-1 microM)-dependent contraction of the longitudinal muscle of the human isolated ileum, which was unaffected by either atropine (1 microM) or tetrodotoxin (1 microM). 2. By contrast, neuromedin U-8 had only a weak effect on the circular muscle of the human isolated ileum. 3. Neuromedin U-8 also produced a concentration-dependent contraction of mucosa-free muscle strips from the dome of the human isolated urinary bladder, its action be...

  9. Transurethral microwave needle ablation for bladder cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@To investigate the role of transurethral microwave needle ablation (TUMWNA) in the management of bladder cancer,TUMWNA was carried out in 24 patients with bladder cancer since 1989. From January 1989 to December 1997, 24 patients with bladder cancer were treated with TUMWNA. The 15 men and 9 women were 42 to 67 years old (mean, 58). There were 18 cases with a single tumor and 6 with multiple tumors (4 with 2 tumors, 1 with 3 and 1 with 4). Tumor diameter ranged from 0.3 to 2.5 cm. The lesions grew in different bladder regions: 13 tumors arose from the fundus, 3 tumors from the dome, 9 from the lateral wall, 5 from the anterior wall, 1 from the triangle region and 2 tumors were situated in the obturator nerve reflex sensitive region.

  10. Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Lurong; Jiang, Guorong; Yao, Fei; Liang, Guoqiang; Wang, Fei; Xu, Heng; Wu, Yan; Yu, Xiao; Liu, Haiyan

    2015-06-01

    Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC. PMID:25975579

  11. Mirtazapine inhibits tumor growth via immune response and serotonergic system.

    Directory of Open Access Journals (Sweden)

    Chun-Kai Fang

    Full Text Available To study the tumor inhibition effect of mirtazapine, a drug for patients with depression, CT26/luc colon carcinoma-bearing animal model was used. BALB/c mice were randomly divided into six groups: two groups without tumors, i.e. wild-type (no drug and drug (mirtazapine, and four groups with tumors, i.e. never (no drug, always (pre-drug, i.e. drug treatment before tumor inoculation and throughout the experiment, concurrent (simultaneously tumor inoculation and drug treatment throughout the experiment, and after (post-drug, i.e. drug treatment after tumor inoculation and throughout the experiment. The "psychiatric" conditions of mice were observed from the immobility time with tail suspension and spontaneous motor activity post tumor inoculation. Significant increase of serum interleukin-12 (sIL-12 and the inhibition of tumor growth were found in mirtazapine-treated mice (always, concurrent, and after as compared with that of never. In addition, interferon-γ level and immunocompetent infiltrating CD4+/CD8+ T cells in the tumors of mirtazapine-treated, tumor-bearing mice were significantly higher as compared with that of never. Tumor necrosis factor-α (TNF-α expressions, on the contrary, are decreased in the mirtazapine-treated, tumor-bearing mice as compared with that of never. Ex vivo autoradiography with [(123I]ADAM, a radiopharmaceutical for serotonin transporter, also confirms the similar results. Notably, better survival rates and intervals were also found in mirtazapine-treated mice. These findings, however, were not observed in the immunodeficient mice. Our results suggest that tumor growth inhibition by mirtazapine in CT26/luc colon carcinoma-bearing mice may be due to the alteration of the tumor microenvironment, which involves the activation of the immune response and the recovery of serotonin level.

  12. Stimuli-responsive nanoparticles for targeting the tumor microenvironment.

    Science.gov (United States)

    Du, Jinzhi; Lane, Lucas A; Nie, Shuming

    2015-12-10

    One of the most challenging and clinically important goals in nanomedicine is to deliver imaging and therapeutic agents to solid tumors. Here we discuss the recent design and development of stimuli-responsive smart nanoparticles for targeting the common attributes of solid tumors such as their acidic and hypoxic microenvironments. This class of stimuli-responsive nanoparticles is inactive during blood circulation and under normal physiological conditions, but is activated by acidic pH, enzymatic up-regulation, or hypoxia once they extravasate into the tumor microenvironment. The nanoparticles are often designed to first "navigate" the body's vascular system, "dock" at the tumor sites, and then "activate" for action inside the tumor interstitial space. They combine the favorable biodistribution and pharmacokinetic properties of nanodelivery vehicles and the rapid diffusion and penetration properties of smaller drug cargos. By targeting the broad tumor habitats rather than tumor-specific receptors, this strategy has the potential to overcome the tumor heterogeneity problem and could be used to design diagnostic and therapeutic nanoparticles for a broad range of solid tumors. PMID:26341694

  13. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  14. Analysis of intravesical recurrence after bladder-preserving therapy for muscle-invasive bladder cancer

    International Nuclear Information System (INIS)

    The aim of the present study was to analyze the pattern of recurrences after bladder-preserving therapy for muscle-invasive bladder cancer. The subjects were 77 patients with T2-3N0M0 bladder cancer whose bladder was preserved by intra-arterial chemotherapy and radiation. The patterns of the first recurrences were retrospectively analyzed. With a median follow-up of 38.5 months, 17 patients (22.1%) experienced intravesical recurrence without metastasis, 14 (82.4%) of which were cases of non-muscle-invasive bladder cancer recurrence and 3 (17.6%) of which were muscle-invasive bladder cancer recurrences. Muscle-invasive bladder cancer recurred at the same site as the initial tumor site in all three cases, whereas non-muscle-invasive bladder cancer recurred at different sites in 64% of the patients in that group. The peak hazard of the non-muscle-invasive bladder cancer recurrence was observed at around a year after treatment. Recurrent non-muscle-invasive bladder cancer was of a significantly lower histological grade with lower Ki-67-labeling indices than the initial muscle-invasive bladder cancer. Twelve (85.7%) of 14 patients with non-muscle-invasive bladder cancer recurrence achieved disease-free status. The multivariate analysis revealed that multiplicity, grade and tumor size were significantly correlated with the recurrence (P=0.0001, 0.0442 and 0.0412, respectively). Most of the recurrences after bladder-preserving therapy were cases of non-muscle-invasive bladder cancer. The recurrence pattern and characteristics of the tumors did not differ from those of primary non-muscle-invasive bladder cancer. Patients with high-risk factors would be candidates for prophylactic intravesical therapy for non-muscle-invasive bladder cancer recurrence. (author)

  15. Allopurinol Protects against Ischemia/Reperfusion-Induced Injury in Rat Urinary Bladders

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Shin

    2015-01-01

    Full Text Available Bladder ischemia-reperfusion (I/R injury results in the generation of reactive oxygen species (ROS and markedly elevates the risk of lower urinary tract symptoms (LUTS. Allopurinol is an inhibitor of xanthine oxidase (XO and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α, c-Jun N-terminal kinase (JNK, and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK, and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.

  16. Bladder Schwannoma - A Case Presentation

    OpenAIRE

    Mosier, Andrew D.; Leitman, David A.; Keylock, Joren; Nguyen, David; Grant, David

    2012-01-01

    Bladder schwannomas are exceedingly rare, benign or malignant, nerve sheath tumors that are most often discovered in patients with a known diagnosis of Neurofibromatosis type 1 (NF1). A few sporadic case reports of bladder schwannoma have been published in urologic, obstetric/gynecologic, and pathologic journals. However, this is the first case report in the radiologic literature where computed tomography imaging and radiology-specific descriptions are discussed. Furthermore, the patient pres...

  17. Radiation response of ''clonogenic'' tumor-cell release (CTCR) from NFSA2ALM1 tumors

    International Nuclear Information System (INIS)

    Blocking the release of living tumor-cells from primary tumors would be one way to prevent or control metastatic dissemination. In the past, most tumor-cell-release studies relied on controversial morphological identification of blood-borne tumor cells without assessing clonogenicity. In the present study, a new method for quantification of ''clonogenic'' tumor-cells released into the blood from primary tumors was used. Mice bearing NFSA2ALM1 were irradiated locally with /sup 137/Cs γ-rays followed at designated times by standard 150 Gy thorax irradiation (TXRT) for CTCR assay. The mice were killed 22 hr after TXRT. The lungs were removed and made into cell suspensions by mincing and enzyme digestion. The cell suspensions were plated in 10cm petri dishes in Fischer's medium supplemented with 10% horse serum. Colonies were stained and counted 11 days later. Time course for suppression of CTCR and its dose response relationship for tumor irradiation were determined: CTCR colonies/mouse/22 hr after 10Gy on tumors were 0.8 +- 0.4, 2.3 +- 0.2, 3.2 +- 1.1 for Day 1,2,7, respectively, while unirradiated control showed 25.7 +- 1.5. Dose response relationship curve had a slope of Do=3.8Gy determined at day 1

  18. 膀胱癌复发患者术后体验的质性研究%Qualitative research in postoperative experience for patients with relapsed bladder tumor

    Institute of Scientific and Technical Information of China (English)

    段秀英; 杨欣; 于晶; 冷爽

    2008-01-01

    Objective To understand postoperative experience for patients with relapsed bladder tumor and analyze its influence factors in order to supply references of postoperative nursing for nurses. Methods Patients with relapsed bladder tumot(10 cases) were interviewed and the obtained results underwent analysis and finishing thematically. Results Factors influencing postoperative experience included education haekground,whether having faith and hobbies or not,the disease,medical charge and pressure of future life.The supporting system came from family,group and society. Conclusions Nurses should strengthen mental care and health education based on patients' specific circumstances in order to improve postoperative quality of life.%目的 了解复发膀胱癌患者的术后体验,分析其影响因素,为临床护理人员对患者进行术后护理提供借鉴.方法 通过访谈形式,访问了10例复发膀胱癌患者,将获得的资料进行分析整理,提供主题.结果 影响患者术后体验差异性的因素主要有:文化程度,有无信仰爱好,疾病本身,治疗费用,未来生活等方面的压力;支持系统主要来自家庭、集体、社会3个方面.结论 应根据患者的具体情况,加强心理护理,健康教育,指导患者提高术后生活质量.

  19. Expression of phosphorylated cAMP response element binding protein (p-CREB) in bladder afferent pathways in VIP-/- mice with cyclophosphamide (CYP)-induced cystitis

    DEFF Research Database (Denmark)

    Jensen, Dorthe G; Studeny, Simon; May, Victor;

    2008-01-01

    The expression of phosphorylated cAMP response element binding protein (p-CREB) in dorsal root ganglia (DRG) with and without cyclophosphamide (CYP)-induced cystitis (150 mg/kg, i.p; 48 h) was determined in VIP(-/-) and wild-type (WT) mice. p-CREB immunoreactivity (IR) was determined in bladder...

  20. Long non‑coding RNA‑GAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (C‑C motif) ligand 1 expression.

    Science.gov (United States)

    Cao, Qifeng; Wang, Ning; Qi, Juan; Gu, Zhengqin; Shen, Haibo

    2016-01-01

    Long non‑coding RNAs (lncRNAs) have important roles in diverse biological processes, including transcriptional regulation, cell growth and tumorigenesis. The present study aimed to investigate whether lncRNA‑growth arrest‑specific (GAS)5 regulated bladder cancer progression via regulation of chemokine (C‑C) ligand (CCL)1 expression. The viability of BLX bladder cancer cells was detected using a Cell Counting kit‑8 assay, and cell apoptosis was assessed by annexin V‑propidium iodide double‑staining. The expression levels of specific genes and proteins were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. In addition, cells were transfected with small interfering (si)RNAs or recombinant GAS5 in order to silence or overexpress GAS5, respectively. The results of the present study demonstrated that knockdown of GAS5 expression promoted bladder cancer cell proliferation, whereas overexpression of GAS5 suppressed cell proliferation. Furthermore, knockdown of GAS5 resulted in an increased percentage of cells in S and G2 phase, and a decreased percentage of cells in G1 phase. In addition, the present study performed a hierarchical cluster analysis of differentially expressed lncRNAs in bladder cancer cells and detected that CCL1 overexpression resulted in an upregulation of GAS5, which may improve the ability of cells to regulate a stress response in vitro. Furthermore, knockdown of GAS5 expression increased the mRNA and protein expression of CCL1 in bladder cancer cells. Gain‑of‑function and loss‑of‑function studies demonstrated that GAS5 was able to inhibit bladder cancer cell proliferation, at least in part, by suppressing the expression of CCL1. The results of the present study demonstrated that GAS5 was able to suppress bladder cancer cell proliferation, at least partially, by suppressing the expression of CCL1. The results of the present study may provide a basis for developing novel

  1. A Novel Copper Chelate Modulates Tumor Associated Macrophages to Promote Anti-Tumor Response of T Cells

    OpenAIRE

    Chatterjee, Shilpak; Mookerjee, Ananda; Mookerjee Basu, Jayati; Chakraborty, Paramita; Ganguly, Avishek; Adhikary, Arghya; Mukhopadhyay, Debanjan; Ganguli, Sudipta; Banerjee, Rajdeep; Ashraf, Mohammad; Biswas, Jaydip; Das, Pradeep K; Sa, Gourisankar; Chatterjee, Mitali; Das, Tanya

    2009-01-01

    Background At the early stages of carcinogenesis, the induction of tumor specific T cell mediated immunity seems to block the tumor growth and give protective anti-tumor immune response. However, tumor associated macrophages (TAMs) might play an immunosuppressive role and subvert this anti tumor immunity leading to tumor progression and metastasis. Methodology/Principal Findings The Cu (II) complex, (chelate), copper N-(2-hydroxy acetophenone) glycinate (CuNG), synthesized by us, has previous...

  2. The clinical course of non-muscle invasive bladder cancer after transuretral resection of the tumor with or without subsequent intravesical application of bacillus Calmette-Guérin: The influence of patients gender and age

    Directory of Open Access Journals (Sweden)

    Milošević Radovan

    2015-01-01

    Full Text Available Bacground/Aim. The therapy with intravesical instillation of bacillus Calmette-Guérin (BCG after transurethral resection (TUR of tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC. The role and importance of BCG intravesical therapy in various shape of tumors, were confirmed by our previous investigation. The aim of this study was to examine whether incidence of recurrence and tumor regression differs depending on sex and age of patients. Methods. This study included a total of 899 patients suffering from NIMBC, treated at our institution from January 1, 2007 to March 1, 2013. Two groups of patients were formed: patients underwent TUR + BCG therapy (the group I and the group II with patients in whom TUR was performed as only therapy. These two groups of patients were divided into subgroups of respondents male and female, age 60 years or younger and older than 60 years. Statistical analysis was performed using χ2 test and the Kolmogorov-Smirnov test. Results. This research suggests that if the frequency of recurrence is seen as the only parameter, considering all the subjects, the lowest recurrence rate was determined in the male subjects, aged 60 years and younger who had received BCG after TUR. A high statistical significance was found in the incidence of recurrence in patients younger than 60 years, depending on the response to the therapy, while in those older than 60 years, the difference was at the level of statistical significance. This can be attributed to a certain degree of infravesical obstruction in older men. Conclusions. Sex and age of patients may have a significant influence on the course and outcome of NMIBC. The disease has the most malignant and most aggressive behavior when present in males older than 60 years.

  3. Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response.

    OpenAIRE

    Kavoussi, L R; Brown, E J; Ritchey, J K; Ratliff, T L

    1990-01-01

    Adjuvant intravesical Calmette-Guerin bacillus (BCG) is an effective treatment for superficial bladder cancer. The mechanisms by which BCG mediates antitumor activity are not known. We investigated the initial interaction of BCG with the bladder mucosa to determine whether binding was essential for the development of antitumor activity. Herein, we show that bladder urothelial disruption induced by acrolein, adriamycin, or electrocautery resulted in BCG binding in areas of urothelial damage. B...

  4. Quality of pathologic response and surgery correlate with survival for completely resected bladder cancer following neoadjuvant chemotherapy

    Science.gov (United States)

    Sonpavde, Guru; Goldman, Bryan H.; Speights, V.O.; Lerner, Seth P.; Wood, David P.; Vogelzang, Nicholas J.; Trump, Donald L.; Natale, Ronald B.; Grossman, H. Barton; Crawford, E. David

    2010-01-01

    BACKGROUND In a retrospective study of SWOG-S8710/INT-0080 (radical cystectomy [RC] alone vs 3 cycles of MVAC neoadjuvant chemotherapy [NC] before RC for bladder cancer), factors associated with improved overall survival (OS) included pathologic complete response (pCR) defined as P0, treatment with NC, completion of RC with negative margins and ≥10 pelvic lymph nodes (LNs) removed. METHODS We used stratified Cox regression to retrospectively study the association of quality of pathologic response post-RC with OS in the subset of S8710 patients that received NC and RC with negative margins. RESULTS Of 154 patients who received NC, 68 (44.2%) were bladder cancer followed by pathological P0 and LN- disease correlate with improved OS. A combination of baseline clinical stage and post-RC pathologic stage may better predict OS. PMID:19517476

  5. Initial Results of Bladder Preserving Approach by Chemo-Radiotherapy in Patients with Muscle Invading Transitional Cell Carcinoma

    International Nuclear Information System (INIS)

    This study was conducted to test the efficacy and tolerability of trimodality treatment for invasive bladder cancer and to test the possibility of bladder sparing. Methods: This study had been carried out on 50 patients with transitional cell carcinoma (TCC) stage T2- T3 tumors with adequate performance status and renal function. All patients were subjected to maximum transurethral resection of bladder tumors (TURBT). Patients were then subjected to chemo-radiation that was executed in two treatment phases. Phase I was external radiotherapy in the form of 46 Gy /23 fractions /5 weeks to whole pelvis with concurrent cisplatin 40 mg/m2 weekly. Phase II was 20 Gy /10 fractions /2 weeks to the bladder tumor with concurrent cisplatin 40 mg/m2 weekly. After phase I, patients who had complete response (CR) or partial response (PR) were subjected to phase II and patients who had stationary disease (SD) were subjected to salvage cystectomy. After the end of treatment, patients who had CR were subjected to bladder preservation. Radiological and cystoscopic reevaluation was done to assess the tumor response after phase I and phase II. After completion of the scheduled treatment, patients were under follow up for clinical examination, radiological, and cystoscopic assessment. Results: The treatment schedule was tolerable and was associated with infrequent incidence of moderate toxicity that was easily controlled without interruption of treatment. Bladder preservation was achieved in 72% of patients. The actuarial relapse free survival and overall survival at a median follow up 18 months for patients who were candidate for bladder preservation were 81% and 100%; respectively. Invasive recurrence (16%) sal-Jvaged with cystectomy and superficial recurrence (6%) successfully treated with Bacilles bilie de Calmette- Guerin. Conclusions: This study indicates that in spite of a relatively small number of patients and short follow-up period; the trimodality treatment could be an

  6. [Contribution to tumor escape and chemotherapy response: A choice between senescence and apoptosis in heterogeneous tumors].

    Science.gov (United States)

    Jonchère, Barbara; Vétillard, Alexandra; Toutain, Bertrand; Guette, Catherine; Coqueret, Olivier

    2016-01-01

    Understanding adaptive signaling pathways in response to chemotherapy is one of the main challenges of cancer treatment. Activated in response to DNA damage, cell cycle and mitotic checkpoints activate the p53-p21 and p16-Rb pathways and induce apoptosis or senescence. Since senescent cells survive and produce a secretome that influences neighbouring cells, it is not particularly clear whether these responses are equivalent and if tumor cells escape these two suppressive pathways to the same extent. Predicting escape is also complicated by the fact that cancer cells adapt to treatments by activating the epithelial-mesenchymal transition and by producing clones with cancer-initiating cells features. Dedifferentiation pathways used in stressful conditions reconstitute dividing and sometimes more aggressive populations in response to chemotherapy. These observations illustrate the importance of tumor heterogeneity and the adaptation capacities of different intra-tumoral subclones. Depending on their oncogenic profile, on their localisation within the tumor and on their interaction with stromal cells, these subclones are expected to have different responses and adaptation capacities to chemotherapy. A complete eradication will certainly rely on combination therapies that can kill at the same time the bulk of the sensitive tumor but can also prevent plasticity and the generation of persistent clones. PMID:26762946

  7. Small cell carcinoma of the urinary bladder

    OpenAIRE

    Pant-Purohit, Mukta; López Beltrán, Antonio; Montironi, Rodolfo; MacLennan, Gregory T.; Cheng, Lian

    2010-01-01

    Small cell carcinoma of the urinary bladder(SCCUB) is a rare and aggressive cancer of the bladder.SCCUB is part of neuroendocrine family of tumors thataffect several organ systems including respiratory,gastrointestinal and male and female genitourinary tract.SCCUB affect males predominantly with common riskfactors include smoking, bladder calculi, bladdermanipulation, and chronic cystitis. Prognosis of SCCUBremains poor due to high metastatic potential and lack ofsymptoms in earlier stages of...

  8. Bladder exstrophy repair

    Science.gov (United States)

    Bladder birth defect repair; Everted bladder repair; Exposed bladder repair; Repair of bladder exstrophy ... in boys and is often linked to other birth defects. Surgery is necessary to: Allow the child to ...

  9. Cystoscopic resection of bladder recurrent tumor by Nd:YAG laser%膀胱镜下Nd:YAG激光治疗膀胱复发性肿瘤疗效观察

    Institute of Scientific and Technical Information of China (English)

    蔡晓晴; 李文光

    2001-01-01

    Purpose:To evaluate the effectiveness and safety of cystoscopic Nd:YAG laser treatment of recurrent bladder tumors.Methods:46 cases of recurrent bladder tumors were treated using Nd:YAG laser cutting and vaporization from june 1995 to february 2000.Results:Nd:YAG laser was effectively used to treat recurrent bladder tumor in 46 patient. There were no intraoperation complications such as bleedding, perforation and delayed complications.Conclusions:It has been demonstrated that Nd:YAG laser therapy is provided with advantages of simple procedure, lower cost, high effect and safety, it can be performed in patients of elder age or in a poor condition with bladder tumor.%目的:探讨膀胱镜下Nd:YAG激光手术治疗膀胱复发性肿瘤的安全性和有效性.方法:对我们1995年6月~2000年2月期间收治的46例膀胱复发性肿瘤患者行膀胱镜下Nd:YAG激光手术治疗.结果:手术全部成功,肿瘤切除彻底,术中和术后无出血、膀胱穿孔等并发症;术后随访6个月~4年以上,异位复发2例,复发率为4.3%.结论:Nd:YAG激光治疗膀胱复发性肿瘤操作简便,安全系数高,效果确切,并具有痛苦少、费用低、无并发症等优点,对年老和体质差的患者尤为适宜,值得推广应用.

  10. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Jae Ho; Lim, Ji Hoon; Seong, Jin Sil; Pyo, Hong Ryull; Koom, Woong Soup; Suh, Chang Ok; Hong, Sung Jun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2001-12-15

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders.

  11. Bladder Preservation by Combined Modality Therapy for Invasive Bladder Cancer: A Five-Year Follow-up

    International Nuclear Information System (INIS)

    Purpose : To determine the long-term results of bladder-preserving approach by transurethral resection of the bladder (TURB), systemic chemotherapy, and radiation therapy for muscle-invasive bladder cancer Methods and materials : From 1991 Jan, through 1994 Dec., 25 patients with muscle invading clinical stage T2 to T4NxM0 bladder cancer were treated width induction by maximal TURB and (arm 1, n=4) three cycles of chemotherapy [MVAC(methotrexate, vincristine, adriamycin, ciplatin)] followed by 64.8 Gy of radiation with concomitant cisplatin, or two cycles of chemotherapy [MCV (methotrexate, ciplatin, vincristine)] after irradiation with concomitant cisplatin (arm 2, n=14), or concurrent chemoradiation only (arm 3, n=7). Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. Those with less than a CR underwent cystectomy. The median follow-up of al patients was 70 months. Results : Most treatment toxicities were mild to moderate. Grade 3 acute hematologic toxicity and chronic cystitis were observed in only 1 and 2 patients, respectively. Overall 5 year survival was 67.3%. Complete remission rate was 80% (20/25). Sixth-three percent of all survivors retained their bladders. In multivariate analysis, prognostic factors that significantly affect survival were T-stage (p=0.013) and Complete remission (p=0.002). Conclusion : Combined modality therapy with TURB, chemotherapy, and radiation has a 67.3% overall 5 year survival rate. This result is similar to cystectomy-based studies for patients of similar clinical stages. Sixty-three percent of long term survivors preserved their bladders

  12. Hypoxia Responsive Drug Delivery Systems in Tumor Therapy.

    Science.gov (United States)

    Alimoradi, Houman; Matikonda, Siddharth S; Gamble, Allan B; Giles, Gregory I; Greish, Khaled

    2016-01-01

    Hypoxia is a common characteristic of solid tumors. It is mainly determined by low levels of oxygen resulting from imperfect vascular networks supplying most tumors. In an attempt to improve the present chemotherapeutic treatment and reduce associated side effects, several prodrug strategies have been introduced to achieve hypoxia-specific delivery of cytotoxic anticancer agents. With the advances in nanotechnology, novel delivery systems activated by the consequent outcomes of hypoxia have been developed. However, developing hypoxia responsive drug delivery systems (which only depend on low oxygen levels) is currently naïve. This review discusses four main hypoxia responsive delivery systems: polymeric based drug delivery systems, oxygen delivery systems combined with radiotherapy and chemotherapy, anaerobic bacteria which are used for delivery of genes to express anticancer proteins such as tumor necrosis alpha (TNF-α) and hypoxia-inducible transcription factors 1 alpha (HIF1α) responsive gene delivery systems. PMID:26898739

  13. Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

    International Nuclear Information System (INIS)

    Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed. Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). Results: Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q

  14. Familial aggregation of bladder cancer

    Directory of Open Access Journals (Sweden)

    Ilić Milena

    2011-01-01

    Full Text Available Background. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Several case reports have described familial aggregation of transitional cell carcinoma of the bladder. Although the majority of patients with bladder cancer do not have family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to the knowledge on the pathogenesis of this disease. The purpose of this study was to describe three cases of urinary bladder cancer in a single three-member family, i.e. in two generations (mother and son and a family member related by marriage (the patient’s wife. Case report. Three cases of urinary bladder cancer occurred in a three-member family within the interval of 5 years. The following common characteristics were detected in our patients: old age (over 60, working as farmers for more than 50 years, negative personal medical history on relevant health disorders, place of birth - village, place of residence - village, the same water supply, similar nutrition, positive family history on urinary bladder cancer or other malignant tumors, the first sign of illness was macroscopic hematuria in all the patients and the same pathohistological type of cancer - carcinoma papillare transitiocellulare. Conclusion. The stated common characteristics in our cases indicate, above all, the impact of exposure to external surrounding factors on the occurrence of urinary bladder cancer.

  15. The granulocyte macrophage–colony stimulating factor surface modified MB49 bladder cancer stem cells vaccine against metastatic bladder cancer

    Directory of Open Access Journals (Sweden)

    Yong-tong Zhu

    2014-07-01

    Full Text Available The MB49 bladder cancer cell vaccine was effective against bladder cancer in the mice model in previous studies. However, part of the tumors regrew as the vaccine could not eliminate the cancer stem cells (CSCs. MB49 bladder cancer stem cells (MCSCs were isolated by a combination of the limited dilution method and the serum free culture medium method. MCSCs possessed higher expression of CD133, CD44, OCT4, NANOG, and ABCG2, the ability of differentiation, higher proliferative abilities, lower susceptibility to chemotherapy, greater migration in vitro, and stronger tumorigenic abilities in vivo. Then streptavidin–mouse granulocyte macrophage–colony stimulating factor (SA–mGM–CSF MCSCs vaccine was prepared. SA–mGM–CSF MCSCs vaccine extended the survival of the mice and inhibited the growth of tumor in protective, therapeutic, memorial and specific immune response experiments. The level of immunoglobulin G and the ratio of dendritic cells and CD4+ and CD8+ T cells were highest in the experimental group when compared to those in other four control groups, as well as for the cytotoxicity assay. We demonstrated that SA–mGM–CSF MCSCs vaccine induces an antitumor immune response to metastatic bladder cancer.

  16. Implantation of Bladder Cancer into the Abdominal Wall; a Case Report

    OpenAIRE

    M Ghafoori; M. Narooinejad; D. Saedi; Asgari, M.

    2006-01-01

    Implantation of high grade and invasive bladder carcinoma into the abdominal wall is not common and can occur as side effects of uninary bladder interventions and surgical procedures, including perforation of bladder wall during transurethral resection of the tumor. Herein, we present a case of implantation of bladder transitional cell carcinoma into abdominal wall into an incisional hernia of a previous small bowel operation; three years after the bladder tumor had been diagnosed and treated...

  17. Advances in identification and application of tumor antigen inducing anti-cancer responses

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Tumor antigen is one of the important bases of tumor immunotherapy[1]. With the discovery of novel tumor antigens, interest in specific immunotherapy for treatment of malignancies has increased substantially. Nowadays more and more scientists paid close attention to various tumor antigens with their roles or/and applications in anti-cancer immune responses, immune tolerance, tumor markers, tumor immunotherapy and so on. Here we discussed the classification of tumor antigens and summarized the technologies of identification and application of tumor antigens.

  18. Small Cell Carcinoma of the Bladder

    Directory of Open Access Journals (Sweden)

    Tufan Cicek

    2015-09-01

    Full Text Available Small Cell Carcinoma of the bladder accounts for less than 1% of all bladder tumors. Small Cell Carcinoma of the bladder has an aggressive behaviour and is usually metastatic at diagnosis. Due to its infrequent occurence, the literature on this entity is limited; which unsurprisingly leads to an uncertanity in defining an ideal therapeutic approach. This report, overviews the literature while describing a 70- year- old female patient who is diagnosed with small cell carcinoma of the bladder arising in an unusual localization. [Cukurova Med J 2015; 40(3.000: 604-608

  19. Changes in Immunogenicity during the Development of Urinary Bladder Cancer: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Wojciech Jóźwicki

    2016-02-01

    Full Text Available In the present study, we evaluated tumor-infiltrating lymphocytes (TILs and blood regulatory T lymphocyte (Tregs, CD4+/CD25+/FoxP3+ expression in bladder cancer patients. The number of CD4+, CD8+, CD25+, FoxP3+ and CD20+ TILs was analyzed in association with clinico-pathomorphological features. In more advanced metastasizing tumors, showing non-classic differentiation (ND and a more aggressive tissue invasion type (TIT, the number of TILs decreased. A low number of CD4+ TILs was associated with poor prognosis. Similarly, Treg frequency before surgery and after surgical treatment was significantly lower in more advanced tumors. The changes in TILs, as well as of local and systemic Tregs, were accompanied by changes in the histological phenotype of urothelial carcinoma regarding pT stage, NDs, TIT, and clinical outcomes. The number of TILs and the frequency of blood Tregs (indicators of antitumor response may be essential for choosing an immunotherapy that is adjusted to the immune status according to the phase of tumor growth. Moreover, a significant reduction in the number of CD4+ and CD8+ TILs with the development of NDs in more advanced tumors may be associated with lower tumor immunogenicity, resulting in immune tolerance towards tumor tissue. These observations and the tendency of urothelial bladder carcinoma to undergo NDs in a heterogeneous manner during tumor progression suggest complex interactions between bladder cancer immunogenicity and stages of tumor progression.

  20. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

  1. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    Directory of Open Access Journals (Sweden)

    Raphael Benjamin J

    2011-07-01

    Full Text Available Abstract Background Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. Methods In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. Results These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. Conclusions We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We

  2. Choline PET for Monitoring Early Tumor Response to Photodynamic Therapy

    OpenAIRE

    Fei, Baowei; Wang, Hesheng; Wu, Chunying; Chiu, Song-mao

    2009-01-01

    Photodynamic therapy (PDT) is a relatively new therapy that has shown promise for treating various cancers in both preclinical and clinical studies. The present study evaluated the potential use of PET with radiolabeled choline to monitor early tumor response to PDT in animal models.

  3. Investigation of low and moderate stage upper urinary tumor with and without concomitant bladder cuff resection%低分期上尿路上皮癌根治手术不加膀胱袖状切除的可行性分析

    Institute of Scientific and Technical Information of China (English)

    刘士军; 张晓威; 袁佳奇; 叶海云; 王晓峰

    2010-01-01

    Objective To evaluate the necessity of concomitant bladder cuff and the possibility of distal ureter sparing surgery during radical nephroureterectomy of low-level upper urinary tract tumors. Methods Clinical data of 73 patients with low-level (Tis-T3 M0 N0 ) tumors of the proximal upper urinary transitional epithelial cancer treated in radical nephroureterectomy in our hospital from 2000 to 2007 were analyzed retrospectively. The medical charts and pathologic specimens of 35 patients with, and 38 patients without, concomitant bladder cuff were reviewed. Results In the 35 patients with concomitant bladder cuff resection, 8 cases (22.9%) recurrence was observed; in the 38 patients without concomitant bladder cuff resection, 8 cases (21.1%) recurrence was observed. There was no difference between both groups(P>0.05). In the 19 patients suffered renal pelvis tumors with concomitant bladder cuff resection, 4 cases (21.1%) recurrence was observed; In the 16 patients suffered ureter tumors with concomitant bladder cuff resection, 4 cases (25 %) recurrence was observed.There is no difference between patients of renal pelvis tumors and of ureter tumors with concomitant bladder cuff(P>0.05). In the 27 patients suffered renal pelvis tumors without concomitant bladder cuff resection, 3 cases (11.1 %) recurrence was observed; in the 11 patients suffered ureter tumors with concomitant bladder cuff, 5 cases (45.5%) recurrence was observed. There was significant different between patients of renal pelvis tumors and of ureter tumors without concomitant bladder cuff (P0.05).经典肾盂癌根治性手术组19例肾盂癌中,肿瘤复发4例(21.1%);16例中上段输尿管癌中,肿瘤复发4例(25.0%),2组肿瘤复发率差异无统计学意义(P>0.05).根治性肾切除组27例肾盂癌中,肿瘤复发3例(11.1%);11例中上段输尿管癌中,肿瘤复发5例(45.5%),2组肿瘤复发率差异有统计学意义(P<0.05).结论 低分期上尿路上皮癌患者可不行膀胱袖状切

  4. MAGE-C2-Specific TCRs Combined with Epigenetic Drug-Enhanced Antigenicity Yield Robust and Tumor-Selective T Cell Responses.

    Science.gov (United States)

    Kunert, Andre; van Brakel, Mandy; van Steenbergen-Langeveld, Sabine; da Silva, Marvin; Coulie, Pierre G; Lamers, Cor; Sleijfer, Stefan; Debets, Reno

    2016-09-15

    Adoptive T cell therapy has shown significant clinical success for patients with advanced melanoma and other tumors. Further development of T cell therapy requires improved strategies to select effective, yet nonself-reactive, TCRs. In this study, we isolated 10 TCR sequences against four MAGE-C2 (MC2) epitopes from melanoma patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. We introduced these TCRs into T cells, pretreated tumor cells of different histological origins with the epigenetic drugs azacytidine and valproate, and tested tumor and self-reactivities of these TCRs. Pretreatment of tumor cells upregulated MC2 gene expression and enhanced recognition by T cells. In contrast, a panel of normal cell types did not express MC2 mRNA, and similar pretreatment did not result in recognition by MC2-directed T cells. Interestingly, the expression levels of MC2, but not those of CD80, CD86, or programmed death-ligand 1 or 2, correlated with T cell responsiveness. One of the tested TCRs consistently recognized pretreated MC2(+) cell lines from melanoma, head and neck, bladder, and triple-negative breast cancers but showed no response to MHC-eluted peptides or peptides highly similar to MC2. We conclude that targeting MC2 Ag, combined with epigenetic drug-enhanced antigenicity, allows for significant and tumor-selective T cell responses. PMID:27489285

  5. A pure microcytic bladder carcinoma synchronous to prostatic adenocarcinoma.

    OpenAIRE

    Vasileios Sakalis; Anastasia Gkotsi; Efrosyni Mylonaki; Aphroditi Pantzaki; Vasileios Rombis

    2011-01-01

    Small cell carcinoma (SCC) or microcytic carcinoma of the urinary bladder is a rare entity comprising approximately 0.5% of all bladder tumors. Due to its rarity, no prospective studies evaluating the most effective treatment have been published in the medical literature. Several cases of bladder SCC have been presented so far. We describe our case report and we revise the recent literature. Our patient was diagnosed with pure bladder SCC and prostatic adenocarcinoma. After the initial and co...

  6. Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report

    OpenAIRE

    Prelaj, Arsela; Rebuzzi, Sara Elena; Magliocca, Fabio Massimo; Speranza, Iolanda; Corongiu, Emanuele; Borgoni, Giuseppe; Perugia, Giacomo; Liberti, Marcello; Bianco, Vincenzo

    2016-01-01

    Patient: Male, 71 Final Diagnosis: Neuroendocrine cancer bladder Symptoms: Dysuria • haematuria Medication: — Clinical Procedure: Transurethral resection of the bladder tumor Specialty: Oncology Objective: Rare disease Background: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, sho...

  7. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

  8. Immunologic response to tumor ablation with irreversible electroporation.

    Directory of Open Access Journals (Sweden)

    Xiaoxiang Li

    Full Text Available BACKGROUND: Irreversible electroporation (IRE is a promising technique for the focal treatment of pathologic tissues, which involves placing minimally invasive electrodes within the targeted region. However, the knowledge about the therapeutic efficacy and immune reactions in response to IRE remains in its infancy. METHODS: In this work, to detect whether tumor ablation with IRE could trigger the immunologic response, we developed an osteosarcoma rat model and applied IRE directly to ablate the tumor. In the experiment, 118 SD rats were randomized into 4 groups: the control, sham operation, surgical resection, and IRE groups. Another 28 rats without tumor cell implantation served as the normal non-tumor-bearing group. We analyzed the changes in T lymphocyte subsets, sIL-2R and IL-10 levels in the peripheral blood one day before operation, as well as at 1, 3, 7,14 and 21 days after the operation. Moreover, splenocytes were assayed for IFN-γ and IL-4 production using intracellular cytokine staining one day before the operation, as well as at 7 and 21 days after operation. RESULTS: We found that direct IRE completely ablated the tumor cells. A significant increase in peripheral lymphocytes, especially CD3(+ and CD4(+ cells, as well as an increased ratio of CD4(+/CD8(+ were detectable 7 days after operation in both the IRE and surgical resection groups. Compared with the surgical resection group, the IRE group exhibited a stronger cellular immune response. The sIL-2R level of the peripheral blood in the IRE group decreased with time and was significantly different from that in the surgical resection group. Moreover, ablation with IRE significantly increased the percentage of IFN-γ-positive splenocytes. CONCLUSION: These findings indicated that IRE could not only locally destroy the tumor but also change the status of cellular immunity in osteosarcoma-bearing rats. This provides experimental evidence for the clinical application of IRE in

  9. Inhibitory role of the small leucine-rich proteoglycan biglycan in bladder cancer.

    Directory of Open Access Journals (Sweden)

    Christian Niedworok

    Full Text Available BACKGROUND: Urothelial bladder cancer is the ninth most common cancer. Despite surgical and chemotherapeutic treatment the prognosis is still poor once bladder cancer progresses to a muscle-invasive state. Discovery of new diagnostic markers and pathophysiologic effectors might help to contribute to novel diagnostic and therapeutic options. The extracellular matrix microenvironment shaped by the extracellular matrix critically affects tumor cell and stroma cell functions. Therefore, aim of the present study was to assess the possible implication of the small leucine-rich proteoglycan biglycan in progression of human urothelial bladder cancer. METHODS AND RESULTS: For this purpose tumor biopsies of 76 bladder cancer patients with different tumor stages (pTa, pT1-T4 were investigated with respect to biglycan expression and correlated with a long-term (10 years clinical follow-up. Interestingly, higher biglycan mRNA expression was associated with higher tumor stages and muscle invasiveness. In vitro knock-down of endogenous biglycan in human urothelial carcinoma cells (J82 cells increased proliferation, whereas addition of recombinant biglycan and overexpression of biglycan inhibited tumor cell proliferation. In line with this growth-inhibitory effect of biglycan, transplantation of J82 cells after knock-down of biglycan resulted in significantly increased growth of subcutaneous xenograft tumors in nude mice in vivo. Furthermore, treatment with two anti-proliferative, multi-receptor tyrosine kinase inhibitors-sunitinib and sorafenib-strongly upregulated biglycan expression. Collectively, the experimental data suggest that high biglycan expression is associated with reduced tumor cell proliferation. In accordance, Kaplan-Meier analysis revealed higher 10-year survival in patients with high biglycan mRNA expression in tumor biopsies. CONCLUSION: In conclusion, the present data suggest that biglycan is an endogenous inhibitor of bladder cancer cell

  10. Evaluation of the response chemotherapy for penile metastasis of bladder cancer using 18F-fluorodeoxyglucose-PET/CT

    OpenAIRE

    Hakan Öztürk

    2015-01-01

    Background: Metachronous penile metastasis of bladder cancer occurs very rarely. The clinical management of the disease involves complex problems, and the disease is associated with a poor prognosis. The common mode of spread to the penis is by the retrograde venous route. Patients and methods: A 68-year-old patient who was diagnosed with invasive bladder cancer underwent 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) for staging purposes. An 18 mm i...

  11. Trimodality bladder-sparing approach without neoadjuvant chemotherapy for node-negative localized muscle-invasive urinary bladder cancer resulted in comparable cystectomy-free survival

    International Nuclear Information System (INIS)

    To retrospectively review the efficacy and organ preservation experience for muscle-invasive bladder cancer by trimodality therapy at our institution. Between July 2004 and February 2012, seventy patients (M/F = 55/15; median age = 69 years) of lymph node negative localized muscle-invasive bladder cancer were treated primarily with trimodality approach including transurethral resection of bladder tumor (TURBT) prior to combined chemotherapy and radiotherapy (CCRT). Radiotherapy consisted of initial large field size irradiation with 3D conformal technique (3D-CRT), followed by cone-down tumor bed boost with intensity modulated radiotherapy (IMRT) technique. The median total doses delivered to bladder tumor bed and whole bladder were 59.4Gy and 40.0Gy, respectively. No patient received neoadjuvant chemotherapy (NAC). Weekly cisplatin was administered during radiotherapy. Toxicity was scored according to the RTOG criteria. Tumor response was evaluated both cystoscopically and radiographically 3 months after treatment. The numbers of patients with T2, T3 and T4 lesions were 41, 16 and 13, respectively. Overall survival (OS) and progression-free survival (PFS) at 2 and 5 year were 65.7%, 51.9% and 50.8%, 39.9%, respectively, after a median follow-up time of 24 months. Local-regional control and distant metastasis free survival at 2 year were 69.8% and 73.5%, respectively. Complete response (CR) rate assessed three month after CCRT was 78.1%. Ten patients (20%) had local recurrence after initial CR (n = 50), 3 of them were superficial recurrence. One patient underwent radical cystectomy after recurrence. The overall 5-year bladder intact survival was 49.0% (95% CI, 35.5% to 62.5%). Acute toxicities were limited to grade 1-2. One patient developed late grade 3 GU toxicity. Our result suggested that trimodality bladder-sparing approach without NAC or dose-intensification could be well-tolerated with a high CR rate and bladder preserving rate for muscle-invasive bladder

  12. A RETROSPECTIVE STUDY OF THE EFFICACY OF CHEMOIRRADIATION IN LOCALLY ADVANCED URINARY BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    Nehru

    2015-04-01

    Full Text Available BACKGROUND : Radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with locally advanced carcinoma of urinary bladder. Furthermore, a significant proportion of patients are deemed unsuitable for surgery due to inoperability, advanced age, and/or comorbid conditions. B ecause of disappointing results with radical cystectomy in terms of survival, as well as the morbidity and decreased quality of life associated with the surgery, bladder - conserving therapies like trimodality (TURBT, concurrent chemoradiation therapy have been gained popularity as the survival rates are nearly equal with radical cystectomy along with functioning bladder. AIM OF STUDY : To study retrospectively the effectiveness of chemoradition therapy in bladder preservation approach in the management of p atients with locally advanced ( I nvasive bladder cancer in medically unfit and unwilling patients for radical cystectomy and those who cannot tolerate combination chemotherapy drugs. METHOD S AND MATERIAL : The data was collected from the patient’s records between 2004 - 2010 who were treated in our Regional cancer hospital. All were biopsy/CT scan proven muscle invasive urinary bladder tumors with T2 – 3, N0, M0 lesions. Post TURBT status. Medi cally unfit and Unwillingness for surgery and underwent concurrent Radiotherapy with weekly cisplatin therapy. And men and / women with age between 45 - 70 years were included in the study. RESULTS : Out of 28 patients 4 (14.29% patients who had good TURP procedure showed complete response , 20(71.43% patients had partial response and 4(14.29% patients showed stable disease. 71.43% patient showed symptomatic response to treatment . CONCLUSION : Being a single agent chemotherapy with radiation and it is feasible without major toxicity and offers a potentially usefulness in locoregional control and symptomatic relief in unfavorable population with invasive bladder cancer. Moreover it

  13. Selective bladder preservation by combined modality therapy for invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

  14. Dose-response in stereotactic irradiation of lung tumors

    International Nuclear Information System (INIS)

    The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1-8 fractions with different fraction doses was used. After a median follow-up of 14 months (2-85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94 Gy at the isocenter and 50 Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control

  15. Microsatellite instability in bladder cancer

    DEFF Research Database (Denmark)

    Gonzalez-Zulueta, M; Ruppert, J M; Tokino, K; Tsai, Y C; Spruck, C H; Miyao, N; Nichols, P W; Hermann, G G; Horn, T; Steven, K

    1993-01-01

    Somatic instability at microsatellite repeats was detected in 6 of 200 transitional cell carcinomas of the bladder. Instabilities were apparent as changes in (GT)n repeat lengths on human chromosome 9 for four tumors and as alterations in a (CAG)n repeat in the androgen receptor gene on the X chr...

  16. Emmprin and Survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Andersen, Lars Dyrskjøt; Maase, Hans von der;

    2007-01-01

    PURPOSE: Cisplatin-containing chemotherapy is the standard of care for patients with locally advanced and metastatic transitional cell carcinoma of the urothelium. The response rate is approximately 50% and tumor-derived molecular prognostic markers are desirable for improved estimation of response...... and survival. EXPERIMENTAL DESIGN: Affymetrix GeneChip expression profiling was carried out using tumor material from 30 patients. A set of genes with an expression highly correlated to survival time after chemotherapy was identified. Two genes were selected for validation by immunohistochemistry...... in an independent material of 124 patients receiving cisplatin-containing therapy. RESULTS: Fifty-five differentially expressed genes correlated significantly to survival time. Two of the protein products (emmprin and survivin) were validated using immunohistochemistry. Multivariate analysis identified emmprin...

  17. Evaluation of the good tumor response of embryonal tumor with abundant neuropil and true rosettes (ETANTR).

    Science.gov (United States)

    Mozes, Petra; Hauser, Péter; Hortobágyi, Tibor; Benyó, Gábor; Peták, István; Garami, Miklós; Cserháti, Adrienne; Bartyik, Katalin; Bognár, László; Nagy, Zoltán; Turányi, Eszter; Hideghéty, Katalin

    2016-01-01

    The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57 months). Survival data are available for 48 children (including our case): the median overall survival is 13.0 months, though 6 (9%) of the children have had a relative long survival (>30 months). The aggressive combined treatment, involving primary surgical tumor removal, adjuvant polychemotherapy, including high-dose chemotherapy with stem cell transplantation, radiotherapy and radiochemotherapy, might play an important role in the longer survival. We have performed a literature review and we present here a multimodal-treated case of a 2- year-old girl with a long survival, who was reoperated when recurrence occurred. The residual tumor demonstrated a good response to temozolomide radiochemotherapy (craniospinal axis + boost) and followed by maintenance temozolomide. The described complex aggressive treatment option might be considered for future cases of this tumor entity. PMID:26373296

  18. Implantation of Bladder Cancer into the Abdominal Wall; a Case Report

    Directory of Open Access Journals (Sweden)

    M. Ghafoori

    2006-05-01

    Full Text Available Implantation of high grade and invasive bladder carcinoma into the abdominal wall is not common and can occur as side effects of uninary bladder interventions and surgical procedures, including perforation of bladder wall during transurethral resection of the tumor. Herein, we present a case of implantation of bladder transitional cell carcinoma into abdominal wall into an incisional hernia of a previous small bowel operation; three years after the bladder tumor had been diagnosed and treated. In evaluating any mass lesion in the abdominal wall, it is important to consider the possibility of bladder tumor implantation.

  19. Bladder filling variation during radiation treatment of prostate cancer: Can the use of a bladder ultrasound scanner and biofeedback optimize bladder filling?

    International Nuclear Information System (INIS)

    Purpose: To investigate the use of a bladder ultrasound scanner in achieving a better reproducible bladder filling during irradiation of pelvic tumors, specifically prostate cancer. Methods and Materials: First, the accuracy of the bladder ultrasound scanner relative to computed tomography was validated in a group of 26 patients. Next, daily bladder volume variation was evaluated in a group of 18 patients. Another 16 patients participated in a biofeedback protocol, aiming at a more constant bladder volume. The last objective was to study correlations between prostate motion and bladder filling, by using electronic portal imaging device data on implanted gold markers. Results: A strong correlation between bladder scanner volume and computed tomography volume (r = 0.95) was found. Daily bladder volume variation was very high (1 Sd = 47.2%). Bladder filling and daily variation did not significantly differ between the control and the feedback group (47.2% and 40.1%, respectively). Furthermore, no linear correlations between bladder volume variation and prostate motion were found. Conclusions: This study shows large variations in daily bladder volume. The use of a biofeedback protocol yields little reduction in bladder volume variation. Even so, the bladder scanner is an easy to use and accurate tool to register these variations

  20. Knockdown of Ki-67 by Dicer-Substrate Small Interfering RNA Sensitizes Bladder Cancer Cells to Curcumin-Induced Tumor Inhibition

    OpenAIRE

    Pichu, Sivakamasundari; Krishnamoorthy, Swapna; Shishkov, Andrei; Zhang, Bi; McCue, Peter; Ponnappa, Biddanda C.

    2012-01-01

    Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a l...

  1. Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.

    Science.gov (United States)

    Imaoka, S; Yoneda, Y; Sugimoto, T; Ikemoto, S; Hiroi, T; Yamamoto, K; Nakatani, T; Funae, Y

    2001-05-26

    Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue. PMID:11311483

  2. Novel bifunctional anthracycline and nitrosourea chemotherapy for human bladder cancer: analysis in a preclinical survival model.

    Science.gov (United States)

    Glaves, D; Murray, M K; Raghavan, D

    1996-08-01

    A hybrid drug [N-2-chloroethylnitrosoureidodaunorubicin (AD312)] that combines structural and functional features of both anthracyclines and nitrosoureas was evaluated in a preclinical survival model of human bladder cancer. To measure the therapeutic activity of AD312, UCRU-BL13 transitional cell carcinoma cells were grown as xenografts in nude mice, and tumor growth rates were compared after i.v. administration of the drug at three dose levels. AD312 treatment at 45 and 60 mg/kg achieved 7-10-fold inhibition of tumor growth and increased host survival by 156 and 249%, respectively. Doses of 60 mg/kg showed optimal therapeutic efficacy, with sustained tumor growth inhibition, an over 2-fold increase in life span, and 40% of mice tumor free ("cured") at 120 days. Tumors were unresponsive to maximum tolerated doses of doxorubicin, a standard anthracycline used as a single agent and in combination therapies for bladder cancer. 1,3-Bis-[2-chloroethyl]-1-nitrosourea was used as a control for the apparently enhanced response of human tumors in murine hosts to nitrosoureas. 1, 3-Bis-[2-chloroethyl]-1-nitrosourea administered in three injections of 20 mg/kg did not cure mice but temporarily inhibited tumor growth by 70% and prolonged survival by 55%; its activity in this model suggests that it may be included in the repertoire of alkylating agents currently used for treatment of bladder cancers. AD312 showed increased antitumor activity with less toxicity than doxorubicin, and its bifunctional properties provide the opportunity for simultaneous treatment of individual cancer cells with two cytotoxic modalities as well as treatment of heterogeneous populations typical of bladder cancers. This novel cytotoxic drug cured doxorubicin-refractory disease and should be investigated for the clinical management of bladder cancer. PMID:9816302

  3. COMBINED TREATMENT OF LOCALLY-ADVANCED BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    I. V. Chernyshev

    2015-01-01

    Full Text Available Bladder cancer (BC is an important clinical and scientific challenge. In 2013, in Russia, the absolute number of patients with first-ever diagnosis of bladder cancer was 12 992 people. There is an increasing proportion of detection of bladder cancer stage I–II disease patterns: 2003–50.8% in 2013–69.6%, while the number of newly diagnosed patients in III and IV clinical stages remains at 30%. The proportion of individuals who completed the treatment of the number of newly diagnosed patients with bladder cancer in 2013, was as follows: only surgical method — 65.4%, 33.5% combined. Purpose. Improvement of the results of treatment of patients with locally advanced bladder cancer. Materials and methods. The main treatment for muscle-invasive bladder cancer is radical cystectomy. In the combined treatment of bladder cancer chemotherapy is the component that systemic exposure to the tumor, the way of regional and distant metastases. The study included 132 patients with locally advanced bladder cancer who were treated for 2005–2013, divided into four groups: NACT + CE — 27 people (20.5%, CE + ACT — 21 (15.9%, NACT + CE + ACT — 21 (15.9% only CE — 63 (47.7%. An important component of treatment has been the use of platinum (cisplatin or carboplatin in Schemes M–VAC and GP. An objective response is possible in 44.7%, and the stabilization process in 40.4% of patients.Results. The clinical effect is evaluated in all patients. In the group of NACT 21% of patients survived for more than 4 years, but did not survive the 5‑year mark. In the group of CE + ACT the indicator achieved only 3‑year survival rate, which amounted to 43%. In the group of CE — none of the patients did not live up to 3 years, with 2‑year survival rate was 30%. In the group of ACT + NCT + CE 3 patients (15% were alive at the time, passed the threshold of the 5‑year survival rate, there is no progression of cancer.Conclusion. Combined treatment mode NACT

  4. Radiation therapy for intracranial germ cell tumors. Predictive value of tumor response as evaluated by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko; Toita, Takafumi; Kakinohana, Yasumasa; Yamaguchi, Keiichiro; Miyagi, Koichi; Kinjo, Toshihiko; Yamashiro, Katsumi; Sawada, Satoshi [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine

    1997-07-01

    This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response during radiation therapy can predict achievement of primary local with radiation therapy alone. Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy). Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years. Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and 100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone and initial tumor volume. The rate of tumor volume response to irradiation assessed by CT was significantly different in those patients who relapsed compared to those who did not relapse. Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy alone. (author)

  5. Alternating chemo-radiotherapy in bladder cancer: A conservative approach

    Energy Technology Data Exchange (ETDEWEB)

    Orsatti, M.; Franzone, P.; Giudici, S. [Istituto Nazionale per la Ricerca sul Cancro, Genova (Switzerland)] [and others

    1995-08-30

    The aim of this Phase II study was to determine a bladder-sparing treatment in patients with invasive bladder cancer, allowing a better quality of life. Objectives were to test toxicity and disease-free and overall survival of patients given an alternated chemo-radiotherapy definitive treatment. Seventy-six patients with bladder cancer Stage T1G3 through T4 N0 M0 were entered in the same chemotherapy regimen (Cisplatin 20 mg/mq and 5-Fluorouracil 200 mg/mq daily for 5 days) alternated with different radiotherapy scheduling, the first 18 patients received two cycles of 20 Gy/10 fractions/12 days each; the second group of 58 patients received two cycles of 25 Gy/10 fractions/12 days each (the last 21 patients received Methotrexate 40 mg/mq instead of 5-Fluorouracil). A clinical complete response was observed in 57 patients (81%), partial response in 7 patients (10%), and a nonresponse in 6 patients (9%). At a median follow-up of 45 months, 33 patients (47%) were alive and free of tumor. The 6-year overall survival and progression-free survival was 42% and 40%, respectively. Systemic side effects were mild, while a moderate or severe local toxicity was observed in 14 patients and 13 patients (about 20%), respectively. Our conservative combination treatment allowed bladder-sparing in a high rate of patients and resulted in a survival comparable to that reported after radical cystectomy. 34 refs., 4 figs., 5 tabs.

  6. Peripheral tumors alter neuroinflammatory responses to lipopolysaccharide in female rats

    OpenAIRE

    Pyter, Leah M.; Bih, Sarah El Mouatassim; Sattar, Husain; Prendergast, Brian J.

    2014-01-01

    Cancer is associated with an increased prevalence of depression. Peripheral tumors induce inflammatory cytokine production in the brain and depressive-like behaviors. Mounting evidence indicates that cytokines are part of a pathway by which peripheral inflammation causes depression. Neuroinflammatory responses to immune challenges can be exacerbated (primed) by prior immunological activation associated with aging, early-life infection, and drug exposure. This experiment tested the hypothesis ...

  7. Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

    DEFF Research Database (Denmark)

    Nascimento e Pontes, Merielen Garcia; da Silveira, Sara Martorelli; Trindade Filho, José Carlos de Souza;

    2013-01-01

    OBJECTIVE: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. METHODS: Tumors and their respective recurren...

  8. 经尿道膀胱肿瘤电切术与绿激光治疗非肌层侵润性膀胱癌的临床效果及预后分析%The Clinical Effect and Prognostic Analysis of Transurethral Resection of Bladder Tumor and Green Laser in the Treatment of Non Muscle Invasive Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    柳坤

    2015-01-01

    目的:探究与分析经尿道膀胱肿瘤电切术和绿激光治疗非肌层浸润性膀胱癌的临床效果及预后。方法选自我院2014年8月~2015年5月收治的非浸润性膀胱癌患者86例,按随机数法分为电切组和激光组,分别给予经尿道电切术和绿激光治疗,观察两组患者手术中的情况以及手术后的情况,将结果进行对比分析。结果激光组患者在术中及术后的不良反应低于电切组,P<0.05,差异具有统计学意义。结论经尿道膀胱肿瘤电切术和绿激光治疗法均能有效治疗非肌层浸润性膀胱癌,绿激光治疗更为安全高效。%Objective To explore and analyze the clinical efficacy and prognosis for patients with non-muscle invasive bladder cancer treated with transurethral bladder tumor resection and green laser. Methods 86 cases of non invasive bladder cancer patients were selected from August 2014 to May 2015 that treated at our hospital. All the patients were divided into two groups, the resection group and the laser group, separately treated with transurethral resection and green laser. The intraoperative and postoperative condition of patients would be analyzed and compared between groups. Results In the laser group, the adverse events of intraoperative and postoperative patients was significantly lower than that of the resection group, P<0.05, compared with statistical significance. Conclusion Transurethral resection of bladder tumor and green laser therapy can effectively treat non-muscle invasive bladder cancer. The green laser treatment is worthy of further research and extension in the clinic with the advantage of more safe and effective..

  9. Immunotherapeutic strategies for bladder cancer.

    Science.gov (United States)

    Chevalier, Mathieu F; Nardelli-Haefliger, Denise; Domingos-Pereira, Sonia; Jichlinski, Patrice; Derré, Laurent

    2014-01-01

    Bladder cancer is a common urologic malignancy with rising incidence in the elderly population. In most cases, bladder cancer is non-muscle-invasive at diagnosis and shows dramatically high recurrence rates, although current treatments often reduce the risk of disease progression. Immunotherapy using intravesical instillation of Bacillus Calmette-Guérin (BCG) remains the most effective therapy for patients with high risk tumors. However, BCG-therapy has important limitations including substantial adverse events and frequent treatment failure. Thus, it appears crucial to either improve or replace current therapy using new immunotherapeutic strategies. Here, we discuss the clinical trials that assessed therapeutic vaccination of bladder cancer patients using tumor associated antigens and we also argue for novel approaches arising from murine models. Vaccination routes to induce appropriate T-cell homing in the tumor site as well as the use of local immunostimulation to enhance recruitment of vaccine-induced T cells are discussed to highlight what we believe is a promising therapeutic vaccination strategy for patients with non-muscle-invasive bladder cancer. PMID:24384699

  10. Ct2 Bladder Cancer.

    Science.gov (United States)

    Soloway, Mark S

    2016-09-01

    The patient is an 80-year-old man who presented with gross hematuria. His past medical history indicates he was a cigarette smoker with 50 pack/years. He was successfully treated for carcinoma of the lung 7 years ago. He received chemotherapy, radiation, and surgery. He has mild COPD but has a good performance status. His laboratory studies do not indicate any abnormalities in terms of renal function. He does not have any significant cardiac disease. He has a medium build. He had prostate cancer and underwent a successful radical prostatectomy 10 years ago. His PSA is undetectable. He has some urinary incontinence and wears two pads/day. He underwent the appropriate investigations for gross hematuria. A CT scan of the abdomen and pelvis was normal with the exception of a 4-cm posterior mass in the bladder. There was no hydronephrosis and no enlarged lymph nodes. He underwent a transurethral resection of a solitary bladder tumor performed by another urologist. The tumor was described as large and sessile. It was located on the posterior wall and was approximately 4 cm. The bimanual examination did not reveal a mass. The pathology report stated that the tumor was a high-grade urothelial carcinoma with invasion into the muscularis propria. There was no lymphovascular invasion. I performed a reTURBT, and at that procedure, I did not identify any obvious tumor but the prior resection site was evident. I resected the prior tumor site quite extensively both in depth and width. The pathology revealed only focal carcinoma in situ. There was ample muscle in the specimen and there was some fat as well. As stated, they were free of any cancer. The patient is receptive to any treatment approach. PMID:27457483

  11. Urogenital tumors

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  12. Pretreatment photosensitizer dosimetry reduces variation in tumor response

    International Nuclear Information System (INIS)

    Purpose: To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment. Methods and Materials: Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. To compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower quartile, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay. Results: Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups. Conclusions: This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency

  13. Histopathological characterization of a syngeneic orthotopic murine bladder cancer model

    Directory of Open Access Journals (Sweden)

    Daher C. Chade

    2008-03-01

    Full Text Available PURPOSE: We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line. MATERIALS AND METHODS: Bladder tumor implantation was achieved by intravesical instillation of 5 x 10(5 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3. After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7, carcinoembrionic antigen (Dako-CEA, p53 and c-erbB2 oncoprotein (Her2/neu. RESULTS: Twenty-nine out of 30 animals (96.7% developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g, 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model. CONCLUSIONS: High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

  14. Apoptosis-related molecular differences for response to tyrosin kinase inhibitors in drug-sensitive and drug-resistant human bladder cancer cells

    Directory of Open Access Journals (Sweden)

    Jixia Li

    2013-01-01

    Full Text Available Context: The epidermal growth factor receptor (EGFR family is reportedly overexpressed in bladder cancer, and tyrosine kinaseinhibitors (TKIs have been suggested as treatment. Gefitinib is a selective inhibitor of the EGFR and lapatinib is a dual inhibitor of both the EGFR and HER2 (human EGFR type 2 receptor. Both compounds compete with the binding of adenosine triphosphate (ATP to the tyrosine kinase domain of the respective receptors to inhibit receptor autophosphorylation causing suppression of signal transduction. Unfortunately, resistance to these inhibitors is a major clinical problem. Aims: To compare the apoptosis signaling pathway(s induced by gefitinib and lapatinib, in UM-UC-5 (drug-sensitive and UM-UC-14 (drug-resistant bladder cancer cells and to identify molecular differences that might be useful predictors of their efficacy. Materials and Methods: Cell proliferation, cell cycle and apoptosis assay were used to detect the effect of TKIs on UM-UC-5 and UM-UC-14 cells. Molecular differences for response to TKIs were examined by protein array. Results: TKIs strongly inhibited cell proliferation and induced cell cycle G1 arrest and apoptosis in UM-UC-5 cells. Most notable apoptosis molecular differences included decreased claspin, trail, and survivin by TKIs in the sensitive cells. In contrast, TKIs had no effect on resistant cells. Conclusions: Claspin, trail, and survivin might be used to determine the sensitivity of bladder cancers to TKIs.

  15. Scavenger receptor-targeted photodynamic therapy of J774 tumors in mice: tumor response and concomitant immunity

    Science.gov (United States)

    Hamblin, Michael R.; O'Donnell, David A.; Huzaira, Misbah; Zahra, Touqir

    2002-06-01

    J774 is a cell line derived from Balb/c mice that in vitro behaves as macrophages (including scavenger-receptor expression) and has been widely used to study macrophage cell biology. In vivo it produces histiocytic lymphoma tumors that are invasive and metastatic. We report here on the response of subcutaneous J774 tumors to photodynamic therapy with scavenger-receptor targeted chlorin(e6). Bovine serum albumin was covalently conjugated with chlorin(e6), maleylated and purified by acetone precipitation and both this and free chlorin(e6) were injected IV into mice at 2 mg/kg. When tumors were illuminated with 665 nm laser-light after 24 hours there was a highly significant response (tumor volume and growth rate) for the conjugate, but this led to a relatively small survival increase due to the highly metastatic nature of the tumor. The free chlorin(e6) gave very little tumor response. When light was delivered 3 hours after injection the response from the conjugate disappeared due to insufficient time for the tumor cells to take up the photosensitizer by receptor-mediated endocytosis. Free chlorin(e6) at 3 hours, however, produced a total regression of the tumors due to a primarily vascular effect, but the mice died sooner than control animals. When J774 tumors were surgically removed at different times after implantation the mouse survival was proportional to the length of time they had had the tumor. We interpret this data to show that mice with J774 tumors slowly develop concomitant immunity and a PDT regimen that swiftly ablates the tumor will give worse survival results than a regimen with a slower tumor response.

  16. Control of the adaptive immune response by tumor vasculature

    Directory of Open Access Journals (Sweden)

    Laetitia eMauge

    2014-03-01

    Full Text Available The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by abnormal vessel structure and permeability, and by specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intratumoral immune responses and contribute to the development of intratumoral immunosuppression, which is a major mechanism for promoting the development, progression and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of antitumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy.

  17. Mechanical disruption of tumors by iron particles and magnetic field application results in increased anti-tumor immune responses.

    Directory of Open Access Journals (Sweden)

    Myriam N Bouchlaka

    Full Text Available The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer.

  18. Differential response of idiopathic sporadic tumoral calcinosis to bisphosphonates

    Directory of Open Access Journals (Sweden)

    Karthik Balachandran

    2014-01-01

    Full Text Available Context: Tumoral calcinosis is a disorder of phosphate metabolism characterized by ectopic calcification around major joints. Surgery is the current treatment of choice, but a suboptimal choice in recurrent and multicentric lesions. Aims: To evaluate the efficacy of bisphosphonates for the management of tumoral calcinosis on optimized medical treatment. Settings and Design: The study was done in the endocrine department of a tertiary care hospital in South India. We prospectively studied two patients with recurrent tumoral calcinosis who had failed therapy with phosphate lowering measures. Materials and Methods: After informed consent, we treated both patients with standard age adjusted doses of bisphosphonates for 18 months. The response was assessed by X ray and whole body 99mTc-methylene diphosphonate bone scan at the beginning of therapy and at the end of 1 year. We also estimated serum phosphate levels and urinary phosphate to document serial changes. Results: Two patients (aged 19 and 5 years with recurrent idiopathic hyperphosphatemic tumoral calcinosis, following surgery were studied. Both patients had failed therapy with conventional medical management − low phosphate diet and phosphate binders. They had restriction of joint mobility. Both were given standard doses of oral alendronate and parenteral pamidronate respectively for more than a year, along with phosphate lowering measures. At the end of 1 year, one of the patients had more than 95% and 90% reduction in the size of the lesions in right and left shoulder joints respectively with total improvement in range of motion. In contrast, the other patient (5-year-old had shown no improvement, despite continuing to maintain normophosphatemia following treatment. Conclusions: Bisphosphonate therapy in tumoral calcinosis is associated with lesion resolution and may be used as a viable alternative to surgery, especially in cases with multicentric recurrence or treatment failure to other

  19. Overall survival and local control following combined modality therapy and selective bladder preservation for invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose/Objective: Bladder preservation, in the interest of quality of life, is secondary to the primary treatment goal of curing the patient. To evaluate the long term efficacy of a selective bladder preserving approach we updated our prospective series which now includes 40 patients surviving and under surveillance for 5 or more years. Materials and Methods: From 1986 through 1993, 106 patients (median age 68 years) with muscle-invading tumor (stages T2-T4a, Nx, M0) initiated a protocol of maximal transurethral resection followed by 2 cycles of methotrexate, cisplatin and vinblastine plus cisplatin x2 with 40Gy pelvic irradiation. Complete responders and all non-cystectomy candidates received consolidation by cisplatin and 24.8Gy. Incomplete responders underwent immediate radical cystectomy as did those who developed recurrent invasive tumor. Median follow-up is 53 months. Results: Of all 106 patients who initiated induction Combined Modality Treatment (CMT): 1) 83 patients or 78% completed CMT; 33% developed moderate or severe leukopenia, 2) 74 patients (70%) had a Complete Response (CR), 3) the 5 year actuarial overall survival is 52%; for clinical stage T2 and T3-T4a this is 63% and 45%, respectively, 4) 36 patients (34%) have had cystectomy, all for tumor (6 because CMT wasn't tolerated, 13 for < CR, 17 for recurrence); no patient required cystectomy for complications; the 5 year survival with an intact functioning bladder is 43%, 5) 31 patients (20%) have had relapse of a superficial TCC with 4 requiring cystectomy after failing conservative management with a subsequent median follow-up of 58 months. Conclusion: These data demonstrate 1) that induction CMT with transurethral surgery and chemo-radiotherapy and selection for organ-conservation by response have a 52% overall survival which is comparable to immediate cystectomy-based prospective studies of patients with similar age and clinical stages and 2) that the majority of long term survivors retain fully

  20. A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer. A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Miyanaga, Naoto; Akaza, Hideyuki [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Okumura, Toshiyuki [and others

    2000-02-01

    A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. lntra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function. (author)

  1. 5-Hydroxytryptamine-induced bladder hyperactivity via the 5-HT2A receptor in partial bladder outlet obstruction in rats.

    Science.gov (United States)

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-04-01

    We investigated the effects of partial bladder outlet obstruction (BOO) on the function and gene expression of 5-hydroxytryptamine (5-HT) receptor subtypes in rat bladder. Isometric contractions of the isolated bladders from sham-operated control and BOO rats were examined. The contractile responses to 5-HT were significantly increased in BOO rat bladder strips, while the responses to KCl, carbachol, or phenylephrine were not different from the control. The 5-HT-induced hypercontraction in BOO rat bladder strips was inhibited by ketanserin, a 5-HT(2A) receptor antagonist. The contractile responses to 5-HT in bladder strips were not affected by urothelium removal from the intact bladder. The gene expression of 5-HT receptor subtypes in the bladders was analyzed by RT-PCR. The mRNA expression of the 5-HT(2A), 5-HT(2B), 5-HT(2C), 5-HT(4), and 5-HT(7) receptors was detected in both the control and BOO rat bladders. Quantitative RT-PCR analysis showed there was a significant increase of 5-HT(2A) receptor mRNA in the BOO rat bladder compared with the control bladder. On the other hand, the gene expression of the 5-HT(4) receptor was not changed in the BOO rat bladder. These results suggest that the increased contractile responses to 5-HT in BOO rat bladder may be partly caused by 5-HT(2A) receptor upregulation in the detrusor smooth muscles. PMID:23344575

  2. Knockdown of Ki-67 by dicer-substrate small interfering RNA sensitizes bladder cancer cells to curcumin-induced tumor inhibition.

    Directory of Open Access Journals (Sweden)

    Sivakamasundari Pichu

    Full Text Available Transitional cell carcinoma (TCC of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR. However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma longa, has been shown to possess powerful anticancer properties. In this study, we evaluated the combined efficacy of curcumin and a siRNA against Ki-67 mRNA (Ki-67-7 in rat (AY-27 and human (T-24 bladder cancer cells. The anticancer effects were assessed by the determination of cell viability, apoptosis and cell cycle analysis. Ki-67-7 (10 nM and curcumin (10 µM, when treated independently, were moderately effective. However, in their combined presence, proliferation of bladder cancer cells was profoundly (>85% inhibited; the rate of apoptosis in the combined presence of curcumin and Ki-67-7 (36% was greater than that due to Ki-67-7 (14% or curcumin (13% alone. A similar synergy between curcumin and Ki-67-7 in inducing cell cycle arrest was also observed. Western blot analysis suggested that pretreatment with Ki-67-7 sensitized bladder cancer cells to curcumin-mediated apoptosis and cell cycle arrest by p53- and p21-independent mechanisms. These data suggest that a combination of anti-Ki-67 siRNA and curcumin could be a viable treatment against the proliferation of bladder cancer cells.

  3. Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer

    OpenAIRE

    Morrison, Carl D.; Liu, Pengyuan; Woloszynska-Read, Anna; Zhang, Jianmin; Luo, Wei; Qin, Maochun; Bshara, Wiam; Conroy, Jeffrey M; Sabatini, Linda; Vedell, Peter; Xiong, Donghai; Liu, Song; Wang, Jianmin; Shen, He; Li, Yinwei

    2014-01-01

    Genetic alterations are frequently observed in bladder cancer. In this study, we demonstrate that bladder tumors can be classified into two different types based on the spectrum of genetic diversity they confer. In one class of tumors, we observed tumor protein p53 mutations and a large number of single-nucleotide and structural variants. Another characteristic of this group was chromosome shattering, known as chromothripsis, and mutational heterogeneity. The other two bladder tumors did not ...

  4. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    OpenAIRE

    Sonia Gon; Bipasa Majumdar; Ranjan Kumar Dey; Subrata Kumar Mitra

    2013-01-01

    Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bla...

  5. Iatrogenic neonatal bladder perforation

    Directory of Open Access Journals (Sweden)

    Lilia Trigui

    2011-01-01

    Full Text Available Neonatal bladder rupture is rare as a complication of bladder obstruction due to abnormal anatomy or iatrogenic causes. The present study describes the case of a 3-day-old infant with ascites due to bladder perforation secondary probably to manual decompression of the bladder. The infant underwent successful surgical repair of the perforation.

  6. Early inflammatory response in epithelial ovarian tumor cyst fluids

    International Nuclear Information System (INIS)

    Mortality rates for epithelial ovarian cancer (EOC) are high, mainly due to late-stage diagnosis. The identification of biomarkers for this cancer could contribute to earlier diagnosis and increased survival rates. Given that chronic inflammation plays a central role in cancer initiation and progression, we selected and tested 15 cancer-related cytokines and growth factors in 38 ovarian cyst fluid samples. We used ovarian cyst fluid since it is found in proximity to the pathology and mined it for inflammatory biomarkers suitable for early detection of EOC. Immunoprecipitation and high-throughput sample fractionation were obtained by using tandem antibody libraries bead and mass spectrometry. Two proteins, monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleucin-8 (IL-8/CXCL8), were significantly (P < 0.0001) higher in the malignant (n = 16) versus benign (n = 22) tumor cysts. Validation of MCP-1, IL-8, and growth-regulated protein-α (GROα/CXCL1) was performed with ELISA in benign, borderline, and malignant cyst fluids (n = 256) and corresponding serum (n = 256). CA125 was measured in serum from all patients and used in the algorithms performed. MCP-1, IL-8, and GROα are proinflammatory cytokines and promoters of tumor growth. From 5- to 100-fold higher concentrations of MCP-1, IL-8 and GROα were detected in the cyst fluids compared to the serum. Significant (P < 0.001) cytokine response was already established in borderline cyst fluids and stage I EOC. In serum a significant (P < 0.01) increase of IL-8 and GROα was found, but not until stage I and stage III EOC, respectively. These findings confirm that early events in tumorigenesis can be analyzed and detected in the tumor environment and we conclude that ovarian cyst fluid is a promising source in the search for new biomarkers for early ovarian tumors

  7. Bladder preservation using chemoradiation therapy for locally invasive bladder cancer

    International Nuclear Information System (INIS)

    We investigated the long-term results and molecular markers of outcome with selective organ preservation in invasive bladder cancer using chemoradiation therapy. We examined locally invasive bladder cancer in 32 patients (30 men, 2 women; mean age at treatment 68.1 years) who underwent bladder-sparing protocols in the Department of Urology at Sumitomo Hospital between 2000 and 2005. The clinical stage was T2, T3, and T4 in 13, 16, and 3 patients, respectively. Our protocol includes aggressive transurethral resection of the bladder tumor (TURBT) and 46 Gy radiotherapy (2 Gy/fraction, 5 fractions/week) to the pelvis with concurrent cisplatin chemotherapy (20 mg/body/day, 5 days/week, the first and fourth week, intravenously). The initial evaluation included magnetic resonance imaging (MRI), urine cytology, and cystoscopy with a biopsy. During follow-up, if the patients developed superficial recurrence, they was treated with TURBT and intravesical Bacillus Calmette-Guerin (BCG), while patients with invasive recurrence were advised to undergo a salvage cystectomy. We examined the association between the expression of the Bcl-2 family in pretreatment TUR specimens and patient outcome. The mean follow-up was 54.6 months. The first assessment after the induction chemoradiotherapy showed that bladder preservation was achieved in 27 patients (84.4%). The actuarial local control rate with an intact bladder was 56.3% (18 patients) at 3 years. The 1-, 3-, and 5-year cancer-specific survival rate was 90.6, 84.0, and 66.9%, respectively. The 5-year cancer-specific survival rate was 75.0, 67.2, and 33.3% in T2, T3, and T4, respectively. Bcl-x positivity was significantly associated with a poor cancer-specific survival rate (log-rank test, p=0.038). Chemoradiation therapy for invasive bladder cancer can achieve survival rates similar to those in patients treated with radical cystectomy, with successful bladder preservation. Our results suggest that the expression of Bcl-x is a

  8. Urinary Bladder Leiomyosarcoma: Primary Surgical Treatment.

    Science.gov (United States)

    Slaoui, Hakim; Sanchez-Salas, Rafael; Validire, Pierre; Barret, Eric; Rozet, François; Galiano, Marc; Cathelineau, Xavier

    2014-07-01

    Cases of bladder leiomyosarcoma represent 0.1% of all nonurothelial tumors. We present a case report of a 73-year-old man who underwent a radical cystoprostatectomy for a high-grade bladder leiomyosarcoma with an ileal diversion. The patient recovered uneventfully and no surgical margins were verified in final pathology. Early follow-up at 3 months shows no signs of computed tomography recurrence and adequate adaptation to ileal diversion. Although bladder sarcomas were once thought to have a grim prognosis, recent studies suggest that adequate surgical treatment is able to achieve optimal cancer control outcomes. PMID:26839792

  9. Urinary Bladder Leiomyosarcoma: Primary Surgical Treatment

    Directory of Open Access Journals (Sweden)

    Hakim Slaoui

    2014-07-01

    Full Text Available Cases of bladder leiomyosarcoma represent 0.1% of all nonurothelial tumors. We present a case report of a 73-year-old man who underwent a radical cystoprostatectomy for a high-grade bladder leiomyosarcoma with an ileal diversion. The patient recovered uneventfully and no surgical margins were verified in final pathology. Early follow-up at 3 months shows no signs of computed tomography recurrence and adequate adaptation to ileal diversion. Although bladder sarcomas were once thought to have a grim prognosis, recent studies suggest that adequate surgical treatment is able to achieve optimal cancer control outcomes.

  10. Molecular classification of non-muscle-invasive bladder cancer (pTa low-grade, pT1 low-grade, and pT1 high-grade subgroups) using methylation of tumor-suppressor genes.

    Science.gov (United States)

    Sacristan, Raquel; Gonzalez, Carolina; Fernández-Gómez, Jesus M; Fresno, Florentino; Escaf, Safwan; Sánchez-Carbayo, Marta

    2014-09-01

    The role of epigenetics in distinguishing pathological and clinical subgroups in bladder cancer is not fully characterized. We evaluated whether methylation of tumor-suppressor genes (TSGs) would classify non-muscle-invasive (NMI) bladder cancer subgroups and predict outcome. A retrospective design included the following paraffin-embedded primary NMI tumor types (n = 251): pTa low grade (LG) (n = 79), pT1LG (n = 81), and pT1 high grade (HG) (n = 91). Methylation of 25 TSGs was measured using methylation-specific, multiplex, ligation-dependent probe amplification. The TSGs most frequently methylated in the overall series were STK11 (96.8%), MGMT2 (64.5%), RARB (63.0%), and GATA5 (63.0%). TSG methylation correlated to clinicopathological variables in each subgroup and in the overall NMI series. Methylation of RARB, CD44, PAX5A, GSTP1, IGSF4 (CADM1), PYCARD, CDH13, TP53, and GATA5 classified pTa versus pT1 tumors whereas RARB, CD44, GSTP1, IGSF4, CHFR, PYCARD, TP53, STK11, and GATA5 distinguished LG versus HG tumors. Multivariate analyses indicated that PAX5A, WT1, and BRCA1 methylation independently predicted recurrence in pTaLG, PAX6, ATM, CHFR, and RB1 in pT1LG disease; PYCARD, in pT1HG disease; and PAX5A and RB1, in the overall series. Methylation of TSGs provided a molecular classification of NMI disease according to clinicopathological factors. Furthermore, TSG methylation predicted recurrence in NMI subgroups. PMID:24998186

  11. Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

    Directory of Open Access Journals (Sweden)

    Ramos Kátia L

    2008-11-01

    Full Text Available Abstract Background Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-α and IL-10 expression and to evaluate antitumour activity. Methods For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF-〈 and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells. Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-α in the BCG-treated group, as well as increases in TNF-α and IL-10 mRNA in the rBCG-S1PT group. Conclusion These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-α and IL-10 cytokine productions may have therapeutic value.

  12. Response of the tumor and organs of the tumor-bearing animal to the action of an ionizing radiation

    International Nuclear Information System (INIS)

    Changes in the antioxigenic activity (AOA) of the liver of the tumor-bearing animals and the tumor have been studied after a single whole-body exposure of animals to a dose of 600 R. AOA of the liver of animals having hepatoma 22-a and Ehrlich ascites tumor (EAT) was found to decrease immediately after irradiation while that of the tumor itself can both increase (hepatoma 22-a) and decrease (EAT). Proceeding from the assumption that AOA is connected with tissue radiosensitivity it is suggested that the observed variations in the response of tumor cells and normal tissue to the action of ionizing radiation should be taken into account when developing the schemes of radiation effect on the tumor

  13. Bladder preservation by internal iliac arterial infusion chemotherapy and irradiation in T3 bladder carcinoma patients over the age of 70 years

    Energy Technology Data Exchange (ETDEWEB)

    Hoshi, Senji; Shintaku, Ichiro; Suzuki, Ken-ichi; Takahashi, Toshiko; Kaihou, Yasuhiro; Ishidoya, Shigeto; Namima, Takashige; Ohyama, Chikara; Orikasa, Seiichi [Tohoku Univ., Sendai (Japan). School of Medicine

    2000-12-01

    Treatment by internal iliac arterial infusion chemotherapy (IA) combined with pelvic irradiation has proved to be effective for locally invasive bladder. Eight male patients, median age of 78 years (range 73-81) were enrolled. Pretreatment CT and whole layer core biopsy revealed T3a or T3b. Pelvic CT or fine needle aspiration biopsy following bipedal lymphography revealed N0 in 4 cases, N2 in 2 and N3 in 2, respectively. Three to 7 cycles of cisplatin (CDDP) 30-50 mg/m{sup 2}, methotrexate 20 mg/m{sup 2} and tetrahydropymnyl-adriamycin 20 mg/m{sup 2} every 3 week was administered combined with 40-50 Gy of whole pelvis irradiation. In 4 renal function impaired patients, 100 mg/m{sup 2} of carboplatin was administered instead of CDDP. All patients obtained complete response and the bladders were preserved. Observation periods were from 9 to 75 months (median 37 months). One N2 patient died with metastatic disease and two died without carcinoma. Two patients developed invasive bladder cancer on the side opposite to the primary tumors. Both were successfully treated by IA and irradiation. Bladders of all except one patient functioned for a long period. Side effects of IA and irradiation were not significant. IA combined with pelvic irradiation is effective and safe for elderly patients with bladder carcinoma. (author)

  14. A Case of Giant Bladder Carcinosarcoma without Submucosal Invasion

    OpenAIRE

    Koji Mikami; Mariko Yamanoi; Masayoshi Zaitsu; Akiko Tonooka; Toshimasa Uekusa; Takumi Takeuchi

    2011-01-01

    Carcinosarcoma is a rare biphasic neoplasia containing both malignant mesenchymal and epithelial elements. Bladder carcinosarcoma commonly presented as high-grade, advanced stage, and aggressive behavior with a poor prognosis. An 83-year-old male presented with painless gross hematuria to our hospital. Cystoscopy revealed massive nonpapillary bladder tumor on the right wall. The 91 g tumor could be completely removed with transurethral resection. Histology of the tumor was diagnosed as carcin...

  15. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Richard Choo

    2010-12-01

    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  16. Marker evaluation of human breast and bladder cancers

    Energy Technology Data Exchange (ETDEWEB)

    Mayall, B.H.; Carroll, P.R.; Chen, Ling-Chun; Cohen, M.B.; Goodson, W.H. III; Smith, H.S.; Waldman, F.M. (California Univ., San Francisco, CA (USA))

    1990-11-02

    We are investigating multiple markers in human breast and bladder cancers. Our aim is to identify markers that are clinically relevant and that contribute to our understanding of the disease process in individual patients. Good markers accurately assess the malignant potential of a cancer in an individual patient. Thus, they help identify those cancers that will recur, and they may be used to predict more accurately time to recurrence, response to treatment, and overall prognosis. Therapy and patient management may then be optimized to the individual patient. Relevant markers reflect the underlying pathobiology of individual tumors. As a tissue undergoes transformation from benign to malignant, the cells lose their differentiated phenotype. As a generalization, the more the cellular phenotype, cellular proliferation and cellular genotype depart from normal, the more advanced is the tumor in its biological evolution and the more likely it is that the patient has a poor prognosis. We use three studies to illustrate our investigation of potential tumor markers. Breast cancers are labeled in vivo with 5-bromodeoxyuridine (BrdUrd) to give a direct measure of the tumor labeling index. Bladder cancers are analyzed immunocytochemically using an antibody against proliferation. Finally, the techniques of molecular genetics are used to detect allelic loss in breast cancers. 6 refs., 3 figs.

  17. Transcriptional profiling of the bladder in urogenital schistosomiasis reveals pathways of inflammatory fibrosis and urothelial compromise.

    Directory of Open Access Journals (Sweden)

    Debalina Ray

    Full Text Available Urogenital schistosomiasis, chronic infection by Schistosoma haematobium, affects 112 million people worldwide. S. haematobium worm oviposition in the bladder wall leads to granulomatous inflammation, fibrosis, and egg expulsion into the urine. Despite the global impact of urogenital schistosomiasis, basic understanding of the associated pathologic mechanisms has been incomplete due to the lack of suitable animal models. We leveraged our recently developed mouse model of urogenital schistosomiasis to perform the first-ever profiling of the early molecular events that occur in the bladder in response to the introduction of S. haematobium eggs. Microarray analysis of bladders revealed rapid, differential transcription of large numbers of genes, peaking three weeks post-egg administration. Many differentially transcribed genes were related to the canonical Type 2 anti-schistosomal immune response, as reflected by the development of egg-based bladder granulomata. Numerous collagen and metalloproteinase genes were differentially transcribed over time, revealing complex remodeling and fibrosis of the bladder that was confirmed by Masson's Trichrome staining. Multiple genes implicated in carcinogenesis pathways, including vascular endothelial growth factor-, oncogene-, and mammary tumor-related genes, were differentially transcribed in egg-injected bladders. Surprisingly, junctional adhesion molecule, claudin and uroplakin genes, key components for maintaining the urothelial barrier, were globally suppressed after bladder exposure to eggs. This occurred in the setting of urothelial hyperplasia and egg shedding in urine. Thus, S. haematobium egg expulsion is associated with intricate modulation of the urothelial barrier on the cellular and molecular level. Taken together, our findings have important implications for understanding host-parasite interactions and carcinogenesis in urogenital schistosomiasis, and may provide clues for novel therapeutic

  18. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    Science.gov (United States)

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  19. Bladder pheochromocytoma: case presentation and the use of OctreoScan for localization of extra-adrenal tumor sites in a pediatric patient.

    Science.gov (United States)

    Fournier, José R; Baez-Trinidad, Luis; Acosta, Alex; Marrero, Miguel; Correa-Rivas, María; Rodríguez-Becerra, Javier; Nieves, Francisco

    2008-03-01

    An eleven year old boy presented with headaches and dizziness associated to micturition. On radiologic imaging, he was found with a bladder mass. The biochemical work up was suggestive of pheochromocytoma. An OctreoScan (111In-pentreotide) was used to rule out metastatic extension or other extra-adrenal locations of the pheochromocytoma. OctreoScan data correlated well with other radiologic studies, operative findings and with the final diagnosis, validating its use on pediatric patients. PMID:18450243

  20. Tumor response to radiotherapy is dependent on genotype-associated mechanisms in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Williams Jerry R

    2010-08-01

    Full Text Available Abstract Background We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21 in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy. In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose. Methods We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses. Results Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1 total cells killed as measured in vitro 2 additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose. Conclusions We establish an analytical

  1. Tumor response to radiotherapy is dependent on genotype-associated mechanisms in vitro and in vivo

    International Nuclear Information System (INIS)

    We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21) in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy. In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose. We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses. Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1) total cells killed as measured in vitro 2) additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose. We establish an analytical structure that predicts tumor response to radiotherapy based on

  2. A new optical method improves fluorescence guided diagnosis of bladder tumor in the outpatient department and reveals significant photo bleaching problems in established inpatients PDD techniques

    DEFF Research Database (Denmark)

    Lindvold, Lars René; Hermann, Gregers G.

    2013-01-01

    Photo dynamic diagnosis (PDD) is a convenient and well-documented procedure for diagnosis of bladder cancer and tumours using endoscopic techniques. At present, this procedure is available only for routine use in an operating room (OR) and often with substantial photobleaching effects of the phot......Photo dynamic diagnosis (PDD) is a convenient and well-documented procedure for diagnosis of bladder cancer and tumours using endoscopic techniques. At present, this procedure is available only for routine use in an operating room (OR) and often with substantial photobleaching effects...... light illumination (PDD mode) and white light illumination used for bladder tumour diagnosis and surgery suffers some inherent disadvantages, i.e., photo bleaching in white light that impairs the possibility for PDD as white light usually is used before the blue light for PDD. Based on spectroscopic...... observations of urine and the photoactive dye Protoporphyrin IX used in PDD a novel optical system for use with the cystoscope has been devised that solves the problem of green fluorescence from urine. This and the knowledge of photo-bleaching pitfalls in established systems make it possible to perform PDD...

  3. Regulation of bitter taste responses by tumor necrosis factor.

    Science.gov (United States)

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. PMID:25911043

  4. Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis

    Institute of Scientific and Technical Information of China (English)

    Zhe-Wei Zhang; Jing Xiao; Wei Luo; Bo-Han Wang; Ji-Min Chen

    2015-01-01

    Background:Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities;ATM is the major kinase for DNA damage detection.This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation (IR).Methods:Immunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine.A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses.Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis,while real-time polymerase chain reaction (RT-PCR) assessed changes in messenger RNA levels of p53 and downstream targets responding to IR.Finally,terminal deoxynucleotidyl transferase-dUTP nick end labeling assay.Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis.All of the data were analyzed with a two-tailed Student's t-test.Results:Immunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation ofγH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation.Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis.RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes.The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells.Conclusion:Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

  5. Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer

    Energy Technology Data Exchange (ETDEWEB)

    Folio, Les Roger, E-mail: Les.folio@nih.gov [Lead Radiologist for CT, NIH Radiology and Imaging Sciences, 10 Center Drive, Bethesda, MD 20892 (United States); Turkbey, Evrim B., E-mail: evrimbengi@yahoo.com [Johns Hopkins University, Baltimore, MD 21218 (United States); Steinberg, Seth M., E-mail: steinbes@mail.nih.gov [Head, Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, 9609 Medical Center Drive, Room 2W334, MSC 9716, Bethesda, MD 20892 (United States); Apolo, Andrea B. [Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892 (United States)

    2015-09-15

    Highlights: • It is clear that 2D axial measurements are incomplete assessments in metastatic disease; especially in light of evolving antiangiogenic therapies that can result in tumor necrosis. • Our pilot study demonstrates that taking volumetric density into account can better predict overall survival when compared to RECIST, volumetric size, MASS and Choi. • Although volumetric segmentation and further density analysis may not yet be feasible within routine workflows, the authors believe that technology advances may soon make this possible. - Abstract: Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan–Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2–14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to

  6. Viable tumor volume: Volume of interest within segmented metastatic lesions, a pilot study of proposed computed tomography response criteria for urothelial cancer

    International Nuclear Information System (INIS)

    Highlights: • It is clear that 2D axial measurements are incomplete assessments in metastatic disease; especially in light of evolving antiangiogenic therapies that can result in tumor necrosis. • Our pilot study demonstrates that taking volumetric density into account can better predict overall survival when compared to RECIST, volumetric size, MASS and Choi. • Although volumetric segmentation and further density analysis may not yet be feasible within routine workflows, the authors believe that technology advances may soon make this possible. - Abstract: Objectives: To evaluate the ability of new computed tomography (CT) response criteria for solid tumors such as urothelial cancer (VTV; viable tumor volume) to predict overall survival (OS) in patients with metastatic bladder cancer treated with cabozantinib. Materials and methods: We compared the relative capabilities of VTV, RECIST, MASS (morphology, attenuation, size, and structure), and Choi criteria, as well as volume measurements, to predict OS using serial follow-up contrast-enhanced CT exams in patients with metastatic urothelial carcinoma. Kaplan–Meier curves and 2-tailed log-rank tests compared OS based on early RECIST 1.1 response against each of the other criteria. A Cox proportional hazards model assessed response at follow-up exams as a time-varying covariate for OS. Results: We assessed 141 lesions in 55CT scans from 17 patients with urothelial metastasis, comparing VTV, RECIST, MASS, and Choi criteria, and volumetric measurements, for response assessment. Median follow-up was 4.5 months, range was 2–14 months. Only the VTV criteria demonstrated a statistical association with OS (p = 0.019; median OS 9.7 vs. 3.5 months). Conclusion: This pilot study suggests that VTV is a promising tool for assessing tumor response and predicting OS, using criteria that incorporate tumor volume and density in patients receiving antiangiogenic therapy for urothelial cancer. Larger studies are warranted to

  7. Renal Cell Carcinoma with Concurrent Urothelial Carcinoma of Urinary Bladder and Non-Hodgkin Lymphoma

    OpenAIRE

    Müller, Danko; Tomasović-Lončarić, Čedna; Galešić-Ljubanović, Danica; Heinzl, Renata; Savić, Ivan; Marušić, Petar

    2012-01-01

    We report a case of a 71-year-old male with multiple primary malignancies involving kidney and urinary bladder, combined with synchronous lymphoma. The patient was admitted to the hospital because of painless gross hematuria. Examination revealed tumor of the right kidney and papillary tumor in the urinary bladder and enlarged lymph nodes along aorta and inferior vena cava. Transurethral resection of bladder tumor (TUR), radical nephrectomy of the right kidney and retroperitoneal lymphadenect...

  8. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Rajamahanty, Srinivas; Louie, Brandon; O’Neill, Cormac; Choudhury, Muhammad; Konno, Sensuke

    2009-01-01

    Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim is to prevent multiple recurrences and progression to a more advanced, invasive disease. We here report an 87-year-old white male patient with invasive bladder cancer who received...

  9. Implementation of adaptive radiation therapy for urinary bladder carcinoma - Imaging, planning and image guidance

    International Nuclear Information System (INIS)

    Background: Adaptive radiation therapy (ART) for urinary bladder cancer has emerged as a promising alternative to conventional RT with potential to minimize radiation-induced toxicity to healthy tissues. In this work we have studied bladder volume variations and their effect on healthy bladder dose sparing and intra fractional margins, in order to refine our ART strategy. Material and methods: An online ART treatment strategy was followed for five patients with urinary bladder cancer with the tumors demarcated using Lipiodol. A library of 3-4 predefined treatment plans for each patient was created based on four successive computed tomography (CT) scans. Cone beam CT (CBCT) images were acquired before each treatment fraction and after the treatment at least weekly. In partial bladder treatment the sparing of the healthy part of the bladder was investigated. The bladder wall displacements due to bladder filling were determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment planning CT scans. An ellipsoidal model was applied in order to find the theoretical maximum values for the bladder wall displacements. Moreover, the actual bladder filling rate during treatment was evaluated using the CBCT images. Results: In partial bladder treatment the volume of the bladder receiving high absorbed doses was generally smaller with a full than empty bladder. The estimation of the bladder volume and the upper limit for the intra fractional movement of the bladder wall could be represented with an ellipsoidal model with a reasonable accuracy. Observed maximum growth of bladder dimensions was less than 10 mm in all three orthogonal directions during 15 minute interval. Conclusion: The use of Lipiodol contrast agent enables partial bladder treatment with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder model can be used for the estimation of the bladder volume changes and the upper limit of the bladder wall movement during the treatment

  10. Bladder Cancer Advocacy Network

    Science.gov (United States)

    ... future bladder cancer research through the Patient Survey Network. Read More... Don’t Miss the 2016 BCAN ... Click here for more details Bladder Cancer Advocacy Network 4915 St. Elmo Avenue, Suite 202 Bethesda, Maryland ...

  11. MANAGEMENT OF CARCINOMA BLADDER: A REVIEW LITERATURE

    Directory of Open Access Journals (Sweden)

    Gurinderjit Singh

    2014-12-01

    Full Text Available Carcinoma of the bladder is a disease of the elderly. Bladder cancer is three times more common in males than in females and more common in whites than in blacks. Patients with bladder cancer have a 1% to 4% incidence of synchronous or metachronous upper t ract urothelial tumors. There are many risk factors for urothelial cancer, classified into (1 Genetic (2 chemical exposure, and (3 chronic irritation. Genetic abnormalities associated with CIS include alterations in the retinoblastoma gene (Rb, p53, an d PTEN. Chemical exposure has the most epidemiologic evidence to support it as an inciting agent (Aromatic amines, aniline dyes, and nitrites and nitrates. Chronic irritants include catheters, recurrent urinary track infections, Schistosoma haematobium, a nd irradiation. There are many studies that suggest high water consumption, vitamin intake, and various diets that are beneficial in preventing bladder cancer. However, none of these have shown any clear benefit with respect to prevention.

  12. Optimizing the diagnosis and treatment of bladder cancer using fluorescence cystoscopy and Raman spectroscopy

    NARCIS (Netherlands)

    Draga, R.O.P.

    2013-01-01

    The gold standard for the diagnosis and treatment of bladder cancer is transurethral resection of bladder tumors (TURBT). A relative high recurrence rate and the need for repeated treatments make bladder cancer one the most expensive cancers from diagnosis till death of the patient. The TURBT accoun

  13. Predictive Factors of Tumor Response After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

    International Nuclear Information System (INIS)

    Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumor response to survival and to identify predictive factors for tumor response after chemoradiation. Methods and Materials: From 1998 to 2008, 168 patients with histologically proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluorouracil (5-FU)-based chemotherapy. Analysis of tumor response was based on lowering of the T stage between pretreatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival rates were correlated with tumor response. Tumor response was analyzed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival rates were, of 44.4% and 74.5% in the whole population, 83.4% and 83.4%, respectively, in patients with pathological complete response, 38.6% and 71.9%, respectively, in patients with tumor downstaging, and 29.1and 58.9% respectively, in patients with absence of response. A pretreatment carcinoembryonic antigen (CEA) level of <5 ng/ml was significantly independently associated with pathologic complete tumor response (p = 0.019). Pretreatment small tumor size (p = 0.04), pretreatment CEA level of <5 ng/ml (p = 0.008), and chemotherapy with capecitabine (vs. 5-FU) (p = 0.04) were significantly associated with tumor downstaging. Conclusions: Downstaging and complete response after CRT improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pretreatment CEA level of <5 ng/ml was associated with complete tumor response. Thus, small tumor size, a pretreatment CEA level of < 5ng/ml, and use of capecitabine were associated with tumor downstaging.

  14. Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

    International Nuclear Information System (INIS)

    Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

  15. Immunotherapy for bladder cancer.

    Science.gov (United States)

    Fuge, Oliver; Vasdev, Nikhil; Allchorne, Paula; Green, James Sa

    2015-01-01

    It is nearly 40 years since Bacillus Calmette-Guérin (BCG) was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest benefit in metastatic disease, although the role in superficial bladder cancer remains unclear. PMID:26000263

  16. Pure primary small cell carcinoma of urinary bladder: A rare diagnostic entity

    Directory of Open Access Journals (Sweden)

    Sonia Gon

    2013-01-01

    Full Text Available Small cell carcinoma of the bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for only 0.3-0.7% of all bladder tumors. Since the tumor is very rare, pathogenesis is uncertain. Small cell carcinomas of the urinary bladder are mixed with classic urothelial carcinomas or adenocarcinomas of the bladder in 68% cases, making pure primary small cell carcinoma even a rarer entity. The unknown etiology and natural history of small cell carcinoma of the urinary bladder represent a challenge both to the pathologist and urologists for its diagnosis and treatment, respectively.

  17. Radical nephroureterectomy and cystectomy for ureteral tumor and bladder mixed tumor by laparoscopic combined open surgery%腹腔镜及开放根治性肾输尿管膀胱切除术治疗输尿管癌合并膀胱混合癌1例报告及文献回顾分析

    Institute of Scientific and Technical Information of China (English)

    李国成; 屈卫星; 程永毅; 季晶; 刘全海

    2012-01-01

    Objective;To evaluate the safety and availability of laparoscopic and open radical nephroureterocystec-tomy to the patients with tumors of ureteral tumor complicating with bladder cancer. Methods: Followed up 1 patient who had been performed radical nephroureterocytectomy due to the tumors of unilateral ureteral tumor complicating with invasive bladder cancer. Results; The patient was diagnosed as tumor of unilateral ureter complicating with inva-sive bladder cancer by cystoscope, ureteroscope, ultrasound, intraveneous pyelography and CT. The patient with left ureteral cancer complicating with bladder cancer was performed the operation of laparoscopy radical nephroureterocys-tectomy and open urethral resection and ureterostomy. The total operation time was 480min and bleeding volume was 560 ml without blood transfusion. The recovery time of alimentary tract and the time of free activity were 3 days and 4 days. No obvious complications were observed. Postoperative pathological results showed that the slide were urothe-lial tumors with tumor stage of ureteral cancer T2N0M0 and tumor stage of bladder cancer T2N0M0 complicated by squamous cell carcinoma. The time of follow - up was 10 months without recurrence. Conclusion; Nephroureterocys-tectomy is available to tumor of unilateral ureteral tumor complicating with bladder mixed cancer. The operation under laparoscopy is available and safe, with less trauma and bleeding and faster recovery. Early diagnosis of bladder mixed tumor is difficult. For early diagnosis and treatment of bladder cancer and improve patient survival rates, multiple sites should be drawn when we perform cystoscopy.%目的:探讨腹腔镜和开放根治性肾输尿管膀胱切除术治疗输尿管癌合并膀胱混合癌患者的可行性和安全性.方法:回顾分析1例单侧输尿管癌并浸润性膀胱混合癌,腹腔镜下行根治性肾输尿管膀胱切除术及开放尿流改道手术患者的临床资料并进行随访分析.结果:术

  18. Radiotherapy is an effective treatment for high-risk T1-bladder cancer

    International Nuclear Information System (INIS)

    Purpose: Current treatment options for high-risk superficial T1-bladder cancer (Grade 3, associated Tis, multifocality, tumor diameter>5 cm or multiple recurrences) include early cystectomy or the goal of organ preservation by adjuvant intravesical therapy after transurethral resection (TURB). We have evaluated the efficacy of adjuvant radiotherapy or radiochemotherapy on local control, bladder preservation, recurrence rate and long-term survival after TURB of high-risk T1-bladder cancer. Patients and Methods: From May 1982 to May 1999, a total of 74 patients with T1-bladder cancer were treated by either radiotherapy (n=17) or concomitant radiochemotherapy (n=57) after TURB. Radiotherapy was initiated 4 to 8 weeks after TURB; a median dose of 54 (range; 45 to 60) Gy was applied to the bladder with daily fractions of 1.8 to 2.0 Gy. Since 1985 chemotherapy has been given in the 1st and 5th week of radiotherapy and consisted of cisplatin (25 mg/m2/d) in 33 patients, carboplatin (65 mg/m2/d) was administered in 14 patients with decreased creatine clearance (2/d) and 5-fluorouracil (600 mg/m2/d) was applied to 10 patients. Salvage cystectomy was recommended for patients with refractory disease or invasive recurrences. At the time of analysis, the median follow-up for surviving patients was 57 (range: 3 to 174) months. Results: After radiotherapy/radiochemotherapy, a complete remission at restaging TURB was achieved in 62 patients (83.7%), 35 of whom (47% with regard to the total cohort of the 74 treated patients) have been continuously free of tumor, 11 patients (18%) experienced a superficial relapse and 16 patients (26%) showed tumor progression after initial complete response. Overall-survival was 72% at 5 years and 50% at 10 years with 77% of the surviving patients maintaining their own bladder at 5 years. Negative prognostic factors for cancer-specific survival were non-complete (R1/2) initial TURB (p=0.12) and recurrent disease (p=0.07); combined radiochemotherapy

  19. Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Franklin C. Lee

    2013-01-01

    Full Text Available Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC in the neoadjuvant setting. Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0 and any response (≤pT1. Odds ratios were calculated using multivariate logistic regression. Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64, P=0.03 and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64, P=0.01. Seventy-two patients received GC (n=41 or MVAC (n=31. CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58. Any response (≤pT1 was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71. Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC. Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

  20. Myeloid cell signatures in tumor microenvironment predicts therapeutic response in cancer

    Directory of Open Access Journals (Sweden)

    Achyut BR

    2016-03-01

    Full Text Available Bhagelu R Achyut, Ali S Arbab Tumor Angiogenesis Laboratory, Department of Biochemistry and Molecular Biology, Cancer Center, Georgia Regents University, Augusta, GA, USA Abstract: Tumor microenvironment (TME consists of several immune and nonimmune cell populations including tumor cells. For many decades, experimental studies have depicted profound contribution of TME toward cancer progression and metastasis development. Several therapeutic strategies have been tested against TME through preclinical studies and clinical trials. Unfortunately, most of them have shown transient effect, and have largely failed due to aggressive tumor growth and without improving survival. Solid tumors are known to have a strong myeloid component (eg, tumor-associated macrophages in tumor development. Recent data suggest that therapeutic responses in tumor are characterized by alterations in immune cell signatures, including tumor-associated myeloid cells. Polarized tumor-associated myeloid cells (M1–M2 are critical in impairing therapeutic effect and promoting tumor growth. The present review is intended to compile all the literatures related to the emerging contribution of different populations of myeloid cells in the development of tumor and therapeutic failures. Finally, we have discussed targeting of myeloid cell populations as a combination therapy with chemo-, targeted-, or radiation therapies. Keywords: tumor microenvironment, tumor-associated macrophage, myeloid-derived suppressor cells, therapies, macrophage polarization, radiation, antiangiogenic therapy

  1. Bladder cancer immunotherapy.

    Science.gov (United States)

    Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M

    1982-11-01

    A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy. PMID:6757467

  2. Surgical Treatment of Adrenal Gland Metastasis Originating from Small Cell Carcinoma of the Urinary Bladder

    OpenAIRE

    Minekatsu Taga; Hideaki Ito; Naoya Kusukawa; Yoshiji Miwa; Hironobu Akino; Yoshiaki Imamura; Osamu Yokoyama

    2013-01-01

    We report a rare case of a solitary adrenal metastasis from small cell carcinoma of the urinary bladder that was successfully treated with surgical resection. A 71-year-old man was suffering from bladder tamponade for hematuria. Computed tomography (CT) revealed a bladder tumor at the left wall. The patients underwent radical cystectomy. Histopathological results were obtained in small cell carcinoma of the bladder with muscle invasion. Thus, he received two courses of adjuvant etoposide and ...

  3. Loss of GATA3 in bladder cancer promotes cell migration and invasion

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Kashiwagi, Eiji; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic...

  4. Is human hepatocellular carcinoma a hormone-responsive tumor?

    Institute of Scientific and Technical Information of China (English)

    Massimo Di Maio; Bruno Daniele; Sandra Pignata; Ciro Gallo; Ermelinda De Maio; Alessandro Morabito; Maria Carmela Piccirillo; Francesco Perrone

    2008-01-01

    Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminaryresults have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.

  5. Immunotherapy for bladder cancer

    Directory of Open Access Journals (Sweden)

    Fuge O

    2015-05-01

    Full Text Available Oliver Fuge,1 Nikhil Vasdev,1 Paula Allchorne,2 James SA Green2 1Department of Urology, Lister Hospital, Stevenage, UK; 2Department of Urology, Bartshealth NHS Trust, Whipps Cross Rd, London, UK Abstract: It is nearly 40 years since Bacillus Calmette–Guérin (BCG was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest

  6. Spectrum of Lesions in Cystoscopic Bladder Biopsies -A Histopathological Study

    Directory of Open Access Journals (Sweden)

    Mahesh Kumar U

    2012-04-01

    Full Text Available Background: Diseases of the bladder, particularly inflammation (cystitis, constitute an important source of clinical signs and symptoms. Tumors of the bladder are an important source of both morbidity and mortality. Objectives: 1 To study the histopathological features of various lesions in bladder biopsies. 2 To study the frequency of different pathological lesions, particularly Transitional Cell Carcinoma (TCC in urinary bladder biopsies. Results: Sixty cases of urinary bladder biopsies were received. Out of 60 patients, 43 were males and 17 were females. The spectrum of pathological lesions included inflammations, metaplastic lesions and tumours. Transitional cell carcinoma was the most common tumour seen in this study. A case of paraganglioma and malakoplakia were also seen. Conclusions: Our study has revealed that the bladder tumours are the commonest lesions in cystoscopic biopsies and TCC was the predominant tumour type

  7. Small cell carcinoma of the urinary bladder

    International Nuclear Information System (INIS)

    Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare tumor that exhibits aggressive behavior and accounts for approximately less than 1% of all primary bladder tumors. Small cell carcinoma generally occurs in the lung, accounting for 25% of all pulmonary malignancies. SCCUB exhibits a similar microscopic and immunohistochemical appearance to that of small cell carcinoma of the lung. There is no consensus about the standard therapy, owing to its rarity. Surgical resection seems to be the mainstay of treatment for patients with limited stage, together with neoadjuvant or adjuvant platinum-based chemotherapy. Radiation therapy has same small effect for palliative purposes, as well as being an alternative to radical cystectomy. Patients with advanced stage, although given platinum-based chemotherapy, have a poor prognosis. We herein review epidemiology, clinical presentation, diagnosis, pathological features, and current management of small cell carcinoma of the urinary bladder. (author)

  8. Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

    International Nuclear Information System (INIS)

    Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test. We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals. The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK. Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic test for bladder cancer

  9. Prognostic significance of clinico-pathological parameters in locally advanced bladder cancer

    International Nuclear Information System (INIS)

    Organ preservation should be the main interest in the treatment of patients with locally advanced bladder cancer. The selection of patients for the respective therapy is mainly based on tumor staging, grading and multiplicity. In the present study data from 65 patients with locally advanced bladder tumors treated by an integrated chemo- radio-therapy were evaluated. The cytostatic drugs used were either Cisplatinium (19 patients (29,2 %))or Adriamycin (21 patients (32.3 %)) alone or a combination (25 patients (38,4 %)). Complete remission was achieved in 53 patients (81,5 %). The following parameters were investigated and evaluated for their prognostic significance in a multivariant analysis. 1.) Histology: tumorgrade, tumortype-papillary/solid, infiltration patterns, lymph and/or blood vessel invasion and areas of squamous cell differentiation within the tumor; 2.) Clinic: staging, tumor volume, multiplicity, therapy and hydronephrosis. The predictive value of these parameters in regard to the therapy response of the tumors was calculated. This study actually showed a statistically worse outcome for patients with papillary histology. All other parameters did not show any significance concerning the tumor remission in response to integrated radio-chemo-therapy. (author)

  10. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various

  11. How the devil facial tumor disease escapes host immune responses.

    Science.gov (United States)

    Siddle, Hannah V; Kaufman, Jim

    2013-08-01

    The devil facial tumor disease (DFTD) is a contagious cancer that has recently emerged among Tasmanian devils, rapidly decimating the population. We have recently discovered that DFTD cells lose the expression MHC molecules on the cell surface, explaining how this tumor avoids recognition by host CD8(+) T cells. PMID:24083079

  12. How the devil facial tumor disease escapes host immune responses

    OpenAIRE

    Siddle, Hannah V; Kaufman, Jim

    2013-01-01

    The devil facial tumor disease (DFTD) is a contagious cancer that has recently emerged among Tasmanian devils, rapidly decimating the population. We have recently discovered that DFTD cells lose the expression MHC molecules on the cell surface, explaining how this tumor avoids recognition by host CD8+ T cells.

  13. Bone and lung tumor response following inhalation of transuranic nitrates

    International Nuclear Information System (INIS)

    Eight-hundred five rats exposed to transuranic nitrate aerosols developed 111 lung tumors and 24 bone tumors. Results for 239Pu(NO3)4, 238Pu(NO3)4, and 253Es(NO3)3 were similar, and comparable to what has been shown for the more refractory transuranic oxides

  14. Large Cell Neuroendocrine Carcinoma of Urinary Bladder; Case Presentation

    OpenAIRE

    Ayşegül SARI; Ermete, Murat; Canan SADULLAHOĞLU; Bal, Kaan; Ahmet BOLÜKBAŞI

    2013-01-01

    Large cell neuroendocrine tumor of the urinary bladder is very rare. It is a type of neuroendocrine carcinoma that is morphologically different from small cell carcinoma.This manuscript describes a 67-year-old man who presented with hematuria. Ultrasonogrophic and computer tomography revealed a 5 cm mass in right posterolateral wall of the bladder that invaded perivesical tissue and he subsequently underwent transurethral resection. Microscopic examination showed a tumor with a sheet-like and...

  15. Amygdalin Influences Bladder Cancer Cell Adhesion and Invasion In Vitro

    OpenAIRE

    Jasmina Makarević; Jochen Rutz; Eva Juengel; Silke Kaulfuss; Igor Tsaur; Karen Nelson; Jesco Pfitzenmaier; Axel Haferkamp; Blaheta, Roman A.

    2014-01-01

    The cyanogenic diglucoside amygdalin, derived from Rosaceae kernels, is employed by many patients as an alternative anti-cancer treatment. However, whether amygdalin indeed acts as an anti-tumor agent is not clear. Metastasis blocking properties of amygdalin on bladder cancer cell lines was, therefore, investigated. Amygdalin (10 mg/ml) was applied to UMUC-3, TCCSUP or RT112 bladder cancer cells for 24 h or for 2 weeks. Tumor cell adhesion to vascular endothelium or to immobilized collagen as...

  16. Effects of mild bladder outlet obstruction on rabbit bladder structure and function.

    Science.gov (United States)

    Kuo, H C

    1995-09-01

    Mild bladder outlet obstruction was created in 42 New Zealand white rabbits by placing a 5-mm inner diameter polyethylene tube around the urethra. Periods of obstruction lasted for 1 day (7 rabbits), 3 days (7 rabbits), 1 week (7 rabbits), 2 weeks (6 rabbits), 4 weeks (7 rabbits), 6 weeks (4 rabbits) and 8 weeks (4 rabbits). Whole bladder functional study was performed in control (5 rabbits) and the obstructed bladders. The obstructed bladders increased in weight two-to threefold. There was no significant difference in bladder weight after different periods of obstruction. Electric stimulation showed a diminished response after 3 days of obstruction. Pharmacologic stimulation with 500 microM carbachol revealed a decreased response after obstruction, but intravesical pressure returned to the control level at 6 and 8 weeks of obstruction. However, the bladder weight and the expelling function of the obstructed bladders remained the same as on day 1 of obstruction. Histologic study of control and obstructed bladders revealed that: 1) dense submucosal fibrous tissue developed after 3 days of obstruction, 2) detrusor muscle hypertrophy and hyperplasia were noted with intermuscular collagenous fiber deposition after 2 weeks of obstruction, 3) trabeculation of the bladder wall with hyperplasia of muscular bundles was noted after 2 weeks of obstruction, 4) acute edematous and inflammatory reaction were apparent after 3 days and 1 week of obstruction, but resolved later and 5) degenerative changes of muscular cells were noted at 8 weeks of obstruction. The results show that despite apparent morphologic changes after outlet obstruction, no significant difference was observed in bladder expelling between short-term and long-term infravesical mild outlet obstruction. The bladder contractile apparatus appears to have a compensatory ability after mild outlet obstruction. PMID:8696170

  17. Oral chemoprevention with acetyl salicylic Acid, vitamin d and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, J; Rosenberg, J;

    2013-01-01

    , and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet...

  18. Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

    LENUS (Irish Health Repository)

    Mulsow, J

    2012-02-01

    Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

  19. The combined status of ATM and p53 link tumor development with therapeutic response

    DEFF Research Database (Denmark)

    Jiang, Hai; Reinhardt, H Christian; Bartkova, Jirina;

    2009-01-01

    commonly used by tumors to bypass early neoplastic checkpoints ultimately determine chemotherapeutic response and generate tumor-specific vulnerabilities that can be exploited with targeted therapies. Specifically, evaluation of the combined status of ATM and p53, two commonly mutated tumor suppressor...... genes, can help to predict the clinical response to genotoxic chemotherapies. We show that in p53-deficient settings, suppression of ATM dramatically sensitizes tumors to DNA-damaging chemotherapy, whereas, conversely, in the presence of functional p53, suppression of ATM or its downstream target Chk2...

  20. Immunological response induced by alternated cooling and heating of breast tumor.

    Science.gov (United States)

    Dong, Jiaxiang; Liu, Ping; Zhang, Aili; Xu, Lisa X

    2007-01-01

    A new in-situ thermal physical method combining both cryosurgery and local hyperthermia was used to treat mice bearing 4T1 murine mammary carcinoma. The induced anti-tumor immune response was investigated. The cryo/heat treatment resulted in stimulation of CTL response and attraction of immunocytes into the tumor debris, which correlated well to the tumor rejection in re-implantation. The results suggested that alternated cooling and heating had synergistic effect and might be developed into an alternative modality for tumor therapy. PMID:18002249

  1. Use of the vasodilator sodium nitroprusside during local hyperthermia: effects on tumor temperature and tumor response in a rat tumor model

    International Nuclear Information System (INIS)

    Purpose: The effect of a decrease in the mean arterial blood pressure (MAP) induced by sodium nitroprusside (SNP) on the tumor temperature during hyperthermia (HT), and on the cytotoxic effect of HT, was studied in the BT4An tumor transplanted to the hind limb of BD IX rats. Experiments with two different anesthetics, pentobarbital and the midazolam/fentanyl/fluanisone combination (MFF), were performed to secure reliable conclusions. Methods and Materials: In the tumor response experiments local waterbath HT at 44.0 deg. C was given for 60 min. Sodium nitroprusside was administered as a continuous intravenous infusion to lower the MAP to 60 or 80 mmHg during HT. In two other experiments the temperature at the base of the tumor during HT was measured before and during SNP infusion. In animals without tumor the temperature was measured subcutaneously on the foot during HT with or without SNP-induced hypotension. Results: When SNP was given to lower the MAP to 60 mmHg during HT in MFF anesthetized animals, the median tumor growth time (TGT) was 70 days, compared to 14.5 days in the HT alone group. The corresponding figures were 127 and 12.1 days with pentobarbital anesthesia. In the HT + SNP group, more than 40% cure was observed in both experiments. No cures were seen in any of the other groups. Hyperthermia alone prolonged the TGT slightly, whereas SNP given alone had no effect, compared to controls. When the MAP was lowered to 80 mmHg by SNP infusion during HT (MFF anesthesia), the median TGT was 19.9 days, which was significantly longer than that in the HT alone group (10.9 days). In the MAP range from 60 to 120 mmHg, a nearly linear relationship between the MAP and the tumor temperature was found during HT in MFF anesthetized animals. With both anesthetics, the median temperature at the base of the tumor was about 0.8 deg. C higher during HT when the MAP was lowered to 60 mmHg by SNP. In animals without tumors, the temperature subcutaneously on the foot was 0

  2. Tumor suppressive microRNA-1 mediated novel apoptosis pathways through direct inhibition of splicing factor serine/arginine-rich 9 (SRSF9/SRp30c) in bladder cancer

    International Nuclear Information System (INIS)

    Highlights: ► Tumor suppressive miRNA-1 directly inhibits splicing factor serine/arginine-rich 9 (SRSF9). ► SRSF9 mRNA expression was up-regulated in bladder cancer specimens compared to normal tissues. ► Cell viability (proliferation, migration, and invasion) was reduced in SRSF9 knockdown cells. ► SRSF9 knockdown by miR-1 induced cell apoptosis through caspase-3/7 activation in BC cell lines. -- Abstract: We have previously found that restoration of tumor suppressive microRNA-1 (miR-1), induced cell apoptosis in bladder cancer (BC) cell lines. However, the apoptosis mechanism induced by miR-1 was not fully elucidated. Alternative splicing of mRNA precursors provides cancer cells with opportunities to translate many oncogenic protein variants, which promote cell proliferation and survival under unpreferable condition for cancer development. Serine/arginine-rich (SR) protein family, which involved in alternative pre-mRNA splicing, plays a critical role for regulating apoptosis by splicing apoptosis-related genes. However, transcriptional regulation of SR proteins, themselves, has not been elucidated. In this study, we focused on splicing factor serine/arginine-rich 9 (SRSF9/SRp30c) on the basis of our previous genome-wide gene expression analysis using miR-1-transfected BC cell lines because putative target sites of miR-1 are existed in 3′-untranslated region (UTR) of SRSF9 mRNA. The expression levels of mRNA of SRSF9 were extremely reduced in the miR-1 transfectants. A luciferase activity significantly decreased in the transfectants suggesting that actual binding occurred between miR-1 and 3′UTR of SRSF9 mRNA. Loss-of-function assays demonstrated that significant inhibitions of cell proliferation, migration, and invasion were observed in the si-SRSF9 transfectants. Apoptosis assays demonstrated that cell apoptosis fraction increased and that caspase-3/7 was activated in the si-SRSF9 transfectants. Our data indicated that tumor suppressive miR-1 induces

  3. Tumor suppressive microRNA-1 mediated novel apoptosis pathways through direct inhibition of splicing factor serine/arginine-rich 9 (SRSF9/SRp30c) in bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Hirofumi [Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan); Enokida, Hideki, E-mail: enokida@m.kufm.kagoshima-u.ac.jp [Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan); Chiyomaru, Takeshi; Tatarano, Shuichi; Hidaka, Hideo; Yamasaki, Takeshi; Gotannda, Takenari; Tachiwada, Tokushi [Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan); Nohata, Nijiro [Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba (Japan); Yamane, Takashi [Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan); Seki, Naohiko [Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba (Japan); Nakagawa, Masayuki [Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Tumor suppressive miRNA-1 directly inhibits splicing factor serine/arginine-rich 9 (SRSF9). Black-Right-Pointing-Pointer SRSF9 mRNA expression was up-regulated in bladder cancer specimens compared to normal tissues. Black-Right-Pointing-Pointer Cell viability (proliferation, migration, and invasion) was reduced in SRSF9 knockdown cells. Black-Right-Pointing-Pointer SRSF9 knockdown by miR-1 induced cell apoptosis through caspase-3/7 activation in BC cell lines. -- Abstract: We have previously found that restoration of tumor suppressive microRNA-1 (miR-1), induced cell apoptosis in bladder cancer (BC) cell lines. However, the apoptosis mechanism induced by miR-1 was not fully elucidated. Alternative splicing of mRNA precursors provides cancer cells with opportunities to translate many oncogenic protein variants, which promote cell proliferation and survival under unpreferable condition for cancer development. Serine/arginine-rich (SR) protein family, which involved in alternative pre-mRNA splicing, plays a critical role for regulating apoptosis by splicing apoptosis-related genes. However, transcriptional regulation of SR proteins, themselves, has not been elucidated. In this study, we focused on splicing factor serine/arginine-rich 9 (SRSF9/SRp30c) on the basis of our previous genome-wide gene expression analysis using miR-1-transfected BC cell lines because putative target sites of miR-1 are existed in 3 Prime -untranslated region (UTR) of SRSF9 mRNA. The expression levels of mRNA of SRSF9 were extremely reduced in the miR-1 transfectants. A luciferase activity significantly decreased in the transfectants suggesting that actual binding occurred between miR-1 and 3 Prime UTR of SRSF9 mRNA. Loss-of-function assays demonstrated that significant inhibitions of cell proliferation, migration, and invasion were observed in the si-SRSF9 transfectants. Apoptosis assays demonstrated that cell apoptosis fraction increased and that

  4. Pathological predictive factors for tumor response in locally advanced breast carcinomas treated with anthracyclin-based neoadjuvant chemotherapy

    Directory of Open Access Journals (Sweden)

    Trupti Patel

    2013-01-01

    Conclusion: Pathological parameters like type of tumor, presence of LVE and tumor necrosis in the core biopsy can predict the response to NACT in routine stain. Tumor necrosis and type of breast carcinoma are predictive parameters for tumor responsiveness to NACT. LVE was reliable in predicting axillary lymph node metastasis.

  5. Tetrachloroethylene exposure and bladder cancer risk

    DEFF Research Database (Denmark)

    Vlaanderen, Jelle; Straif, Kurt; Ruder, Avima; Blair, Aaron; Hansen, Johnni; Lynge, Elsebeth; Charbotel, Barbara; Loomis, Dana; Kauppinen, Timo; Kyyronen, Pentti; Pukkala, Eero; Weiderpass, Elisabete; Guha, Neela

    2014-01-01

    BACKGROUND: In 2012, the International Agency for Research on Cancer classified tetrachloroethylene, used in the production of chemicals and the primary solvent used in dry cleaning, as "probably carcinogenic to humans" based on limited evidence of an increased risk of bladder cancer in dry...... cleaners. OBJECTIVES: We assessed the epidemiological evidence for the association between tetrachloroethylene exposure and bladder cancer from published studies estimating occupational exposure to tetrachloroethylene or in workers in the dry-cleaning industry. METHODS: Random-effects meta-analyses were......-analysis demonstrates an increased risk of bladder cancer in dry cleaners, reported in both cohort and case-control studies, and some evidence for an exposure-response relationship. Although dry cleaners incur mixed exposures, tetrachloroethylene could be responsible for the excess risk of bladder cancer because it is...

  6. Monitoring tumor therapeutic response with diffuse optical spectroscopies

    Science.gov (United States)

    Sunar, Ulas

    The diffuse optical technique using Near-Infrared (NIR) light provides a promising means for non-invasive imaging and clinical diagnosis of deep tissues. During the last few years, we have developed a multi-modal diffuse optical technique combining two qualitatively different methodologies: Diffuse Reflectance Spectroscopy (DRS) and Diffuse Correlation Spectroscopy (DCS). This approach permits real-time, non-invasive and simultaneous quantification of tissue hemoglobin concentration, blood oxygen saturation and blood flow. The instrumentation is portable and rapid, and it has enabled us to study tissue responses in a variety of physiological contexts from cancer treatment monitoring to functional imaging of brain. In this thesis I focus on monitoring of tumor responses to therapies in preclinical and clinical contexts. In preclinical applications, I investigate an antivascular therapy in animal models. The effects of an antivascular drug, Combretastatin, were monitored continuously and were found to induce substantial reduction of blood flow and tissue oxygen. The observations of blood flow and oxygenation were then correlated with power Doppler Ultrasound and EF5 (hypoxia biomarker) techniques, respectively. In another animal model application, the chemotherapy drug, Onconase (Onc), was tested. Onc enhances the therapeutic effects of the drug Cisplatin, which is currently used as a chemotherapeutic agent for head and neck patients during chemoradiation therapy. Our observations demonstrated that Onc increased both tissue blood flow and tissue blood oxygenation; we also compared our results with those from MRI/MRS measurements. The diffuse optical technique was then translated to the clinic, i.e. head and neck patients during chemo-radiation therapy. Our pilot study with eight patients revealed significant early changes in hemodynamic parameters suggesting that daily optics-based therapy monitoring during the first two weeks of chemo-radiation therapy may have

  7. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kuiqing; Chen, Xu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Liu, Cheng [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Gu, Peng; Li, Zhuohang; Wu, Shaoxu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Xu, Kewei [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Lin, Tianxin, E-mail: tianxinl@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Huang, Jian, E-mail: urolhj@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China)

    2015-05-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.

  8. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    International Nuclear Information System (INIS)

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway

  9. Deciphering cellular states of innate tumor drug responses

    OpenAIRE

    Graudens, Esther; Boulanger, Virginie; Mollard, Cindy; Mariage-Samson, Régine; Barlet, Xavier; Grémy, Guilaine; Couillault, Christine; Lajémi, Malika; Piatier-Tonneau, Dominique; Zaborski, Patrick; Eveno, Eric; Auffray, Charles; Imbeaud, Sandrine

    2006-01-01

    Background The molecular mechanisms underlying innate tumor drug resistance, a major obstacle to successful cancer therapy, remain poorly understood. In colorectal cancer (CRC), molecular studies have focused on drug-selected tumor cell lines or individual candidate genes using samples derived from patients already treated with drugs, so that very little data are available prior to drug treatment. Results Transcriptional profiles of clinical samples collected from CRC patients prior to their ...

  10. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    International Nuclear Information System (INIS)

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6–neutralizing antibody for 24 hours or stably transfected with IL-6–silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6–silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  11. Role of Interleukin-6 in the Radiation Response of Liver Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Miao-Fen, E-mail: miaofen@adm.cgmh.org.tw [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Hsieh, Ching-Chuan [College of Medicine, Chang Gung University, Taiwan (China); Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); Chen, Wen-Cheng [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China); College of Medicine, Chang Gung University, Taiwan (China); Lai, Chia-Hsuan [Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan (China)

    2012-12-01

    Purpose: To investigate the role of interleukin (IL)-6 in biological sequelae and tumor regrowth after irradiation for hepatic malignancy, which are critical for the clinical radiation response of liver tumors. Methods and Materials: The Hepa 1-6 murine hepatocellular cancer cell line was used to examine the radiation response by clonogenic assays and tumor growth delay in vivo. After irradiation in a single dose of 6 Gy in vitro or 15 Gy in vivo, biological changes including cell death and tumor regrowth were examined by experimental manipulation of IL-6 signaling. The effects of blocking IL-6 were assessed by cells preincubated in the presence of IL-6-neutralizing antibody for 24 hours or stably transfected with IL-6-silencing vectors. The correlations among tumor responses, IL-6 levels, and myeloid-derived suppressor cells (MDSC) recruitment were examined using animal experiments. Results: Interleukin-6 expression was positively linked to irradiation and radiation resistance, as demonstrated by in vitro and in vivo experiments. Interleukin-6-silencing vectors induced more tumor inhibition and DNA damage after irradiation. When subjects were irradiated with a sublethal dose, the regrowth of irradiated tumors significantly correlated with IL-6 levels and MDSC recruitment in vivo. Furthermore, blocking of IL-6 could overcome irradiation-induced MDSC recruitment and tumor regrowth after treatment. Conclusion: These data demonstrate that IL-6 is important in determining the radiation response of liver tumor cells. Irradiation-induced IL-6 and the subsequent recruitment of MDSC could be responsible for tumor regrowth. Therefore, treatment with concurrent IL-6 inhibition could be a potential therapeutic strategy for increasing the radiation response of tumors.

  12. Assessment of Chemotherapy Response Using FDG-PET in Pediatric Bone Tumors: A Single Institution Experience

    OpenAIRE

    Kim, Dong Hwan; Kim, Seung Yeon; Lee, Hyeon Jeong; Song, Bong Sup; Kim, Dong Ho; Cho, Joong Bum; Lim, Jung Sub; Lee, Jun Ah

    2011-01-01

    Purpose Response to neo-adjuvant chemotherapy is an important prognostic factor for osteosarcoma (OS) and the Ewing sarcoma family of tumors (ESFT). [F-18]-fluorodeoxy-D-glucose (FDG)-positron emission tomography (PET) is a non-invasive imaging modality that predicts histologic response to chemotherapy of various malignancies; however, limited data exist about the usefulness of FDG-PET in predicting the histologic response of pediatric bone tumors to chemotherapy. We analyzed the FDG-PET imag...

  13. Heat-shocked tumor cell lysate-pulsed dendritic cells induce effective anti-tumor immune response in vivo

    Institute of Scientific and Technical Information of China (English)

    Jian Qiu; Guo-Wei Li; Yan-Fang Sui; Hong-Ping Song; Shao-Yan Si; Wei Ge

    2006-01-01

    AIM: To study whether heat-shocked tumor cells could enhance the effect of tumor cell lysate-pulsed dendritic cells (DCs) in evoking anti-tumor immune response in vivo.METHODS: Mouse undifferentiated colon cancer cells(CT-26) were heated at 42℃ for 1 h and then frozenthawed. The bone marrow-derived DCs pulsed with heatshocked CT-26 cell lysate (HSCT-26 DCs) were recruited to immunize syngeneic naive BALB/c mice. The cytotoxic activity of tumor specific cytotoxic T lymphocytes (CTLs)in mouse spleen was evaluated by IFN-enzyme-linked immunospot (ELISpot) and LDH release assay. The immunoprophylactic effects induced by HSCT-26 DCs in mouse colon cancer model were compared to those induced by single CT-26 cell lysate-pulsed DCs (CT-26DCs) on tumor volume, peritoneal metastasis and survival time of the mice.RESULTS: Heat-treated CT-26 cells showed a higher hsp70 protein expression. Heat-shocked CT-26 cell lysate pulsing elevated the co-stimulatory and MHC-Ⅱ molecule expression of bone marrow-derived DCs as well as interleukin-12 p70 secretion. The IFN-γ secreting CTLs induced by HSCT-26 DCs were significantly more than those induced by CT-26 DCs (P= 0.002). The former CTLs' specific cytotoxic activity was higher than the latter CTLs' at a serial E/T ratio of 10:1, 20:1, and 40:1. Mouse colon cancer model showed that the tumor volume of HSCT-26 DC vaccination group was smaller than that of CT-26 DC vaccination group on tumor volume though there was no statistical difference between them(24 mm3 vs 8 mm3, P= 0.480). The median survival time of mice immunized with HSCT-26 DCs was longer than that of those immunized with CT-26 DCs (57 d vs 43 d,P= 0.0384).CONCLUSION: Heat-shocked tumor cell lysate-pulsed DCs can evoke anti-tumor immune response in vivo effectively and serve as a novel DC-based tumor vaccine.

  14. Clear cell urothelial carcinoma of the urinary bladder: a case report and review of the literature

    OpenAIRE

    Knez, Virginia M; Barrow, Willis; Lucia, M. Scott; Wilson, Shandra; La Rosa, Francisco G.

    2014-01-01

    Introduction The occurrence of clear cell tumors in the bladder is not uncommon. Clear cell dysplasia is well-described and characterized by focal replacement of transitional mucosa by cells with abundant clear cytoplasm, nuclear enlargement, and a granular chromatin pattern. Clear cells can also be seen in clear cell adenocarcinoma, which is rare, comprising 0.5% to 2.0% of the reported bladder carcinomas. Other clear cell tumors found in the bladder to be considered in the differential diag...

  15. Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

    OpenAIRE

    Gülçin Güler Şimşek; Servet Güreşçi; Ural Oğuz; Ali Ünsal

    2014-01-01

    Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL) in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor.

  16. Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

    Directory of Open Access Journals (Sweden)

    Gülçin Güler Şimşek

    2014-03-01

    Full Text Available Small cell carcinoma of the urinary bladder (SCCUB is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor.

  17. Tumors of the upper urothelium

    International Nuclear Information System (INIS)

    Forty-two cases of malignant tumors of renal pelvis were reviewed: 28 were transitional cell carcinomas; and 14 were squamous cell carcinomas. The natural history and spread of the disease is discussed in detail. Transitional cell carcinomas spread primarily to the ureter (40 percent), followed closely by the renal bed (33 percent) and bladder (30 percent). Squamous cell carcinomas spread primarily through the renal bed (60 percent), followed by the draining lymph nodes (28 percent). The spread to other regions (bones, splanchnic organs, chest, etc.), occurred with relatively less frequency, but more in squamous than transitional cell carcinomas. Transitional cell carcinomas seem to have a longer natural history than squamous cell carcinomas. Recurrences in bladder and the remainder of the urothelium seem to be controlled for relatively long periods of time, while those in lymph nodes and renal bed seem to be rapidly fatal. The results of treatment and factors influencing them are discussed. Patients suffering from transitional cell carcinomas faired better than those with squamous cell carcinomas at the 5 year mark (25 and 15 percent, respectively), but the 10 year results are poor in both. The role of radiotherapy in the treatment of these tumors and the influencing factors are also discussed in detail. The response of these tumors to radiotherapy seems to be akin to that of the lower urothelium (bladder), provided adequate dosage is delivered to the relevant volume at the proper moment in time. (U.S.)

  18. Imaging Tumor Vascularity and Response to Anti-Angiogenic Therapy Using Gaussia Luciferase.

    Science.gov (United States)

    Kantar, Rami S; Lashgari, Ghazal; Tabet, Elie I; Lewandrowski, Grant K; Carvalho, Litia A; Tannous, Bakhos A

    2016-01-01

    We developed a novel approach to assess tumor vascularity using recombinant Gaussia luciferase (rGluc) protein and bioluminescence imaging. Upon intravenous injection of rGluc followed by its substrate coelenterazine, non-invasive visualization of tumor vascularity by bioluminescence imaging was possible. We applied this method for longitudinal monitoring of tumor vascularity in response to the anti-angiogenic drug tivozanib. This simple and sensitive method could be extended to image blood vessels/vasculature in many different fields. PMID:27198044

  19. Perfusion and Volume Response of Canine Brain Tumors to Stereotactic Radiosurgery and Radiotherapy.

    OpenAIRE

    Zwingenberger, AL; Pollard, RE; Taylor, SL; Chen, RX; Nunley, J; Kent, MS

    2016-01-01

    Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) are highly conformal, high-dose radiation treatment techniques used to treat people and dogs with brain tumors.To evaluate the response to SRS- and SRT-treated tumors using volume and perfusion variables and to measure the survival times of affected dogs.Prospective study of 34 dogs with evidence of brain tumors undergoing stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT).Computed tomography and MRI imaging w...

  20. Frankincense oil derived from Boswellia carteri induces tumor cell specific cytotoxicity

    Directory of Open Access Journals (Sweden)

    Ashley Richard A

    2009-03-01

    Full Text Available Abstract Background Originating from Africa, India, and the Middle East, frankincense oil has been important both socially and economically as an ingredient in incense and perfumes for thousands of years. Frankincense oil is prepared from aromatic hardened gum resins obtained by tapping Boswellia trees. One of the main components of frankincense oil is boswellic acid, a component known to have anti-neoplastic properties. The goal of this study was to evaluate frankincense oil for its anti-tumor activity and signaling pathways in bladder cancer cells. Methods Frankincense oil-induced cell viability was investigated in human bladder cancer J82 cells and immortalized normal bladder urothelial UROtsa cells. Temporal regulation of frankincense oil-activated gene expression in bladder cancer cells was identified by microarray and bioinformatics analysis. Results Within a range of concentration, frankincense oil suppressed cell viability in bladder transitional carcinoma J82 cells but not in UROtsa cells. Comprehensive gene expression analysis confirmed that frankincense oil activates genes that are responsible for cell cycle arrest, cell growth suppression, and apoptosis in J82 cells. However, frankincense oil-induced cell death in J82 cells did not result in DNA fragmentation, a hallmark of apoptosis. Conclusion Frankincense oil appears to distinguish cancerous from normal bladder cells and suppress cancer cell viability. Microarray and bioinformatics analysis proposed multiple pathways that can be activated by frankincense oil to induce bladder cancer cell death. Frankincense oil might represent an alternative intravesical agent for bladder cancer treatment.

  1. Correlation between radiologic evaluation modalities and histologic tumor response in chemotherapy-treated Ewing sarcoma

    International Nuclear Information System (INIS)

    In Ewing sarcoma, the addition of preoperative and postoperative chemotherapy has dramatically raised the 5-year survival rate. Radiologic evaluation of chemotherapy response becomes important so that the treatment plan can be altered in cases of poor response. The authors evaluated sequential examinations, including plain radiographs, Tc-99m skeletal scintigrams, and CT scans in 48 patients with Ewing sarcoma of bone. In 31 patients, biopsy material was obtained for histologic grading of treatment response. Good tumor response (grades 3 and 4) led over the ensuing 1-3 months to disappearance of the soft-tissue tumor component, solid transformation of the previously lamellated or spiculated periosteal reaction, and filling in of the lytic regions. Insufficient tumor response (grades 1 and 2) demonstrated persistence of soft-tissue tumor component and lamellated or spiculated periosteal reaction as well as absence, filling in, or even enlargement of lytic regions

  2. Rectal cancer: the influence of tumor proliferation on response to preoperative irradiation

    International Nuclear Information System (INIS)

    Purpose: Regression of rectal carcinoma after preoperative irradiation is variable, likely reflecting differences in the physical and biologic properties of these tumors. This study examines the association between the pathologic response of rectal cancer after irradiation and its pretreatment proliferative state as assayed by the activity of the proliferative dependent antigens (Ki-67, PCNA) and mitotic counts. Methods and Materials: One hundred and twenty-two patients with locally advanced rectal cancer received preoperative irradiation followed by surgery. Pretreatment tumor biopsies were scored for the extent of Ki-67 and PCNA immunostaining and the number of mitoses per 10 high-powered fields. Postirradiation surgical specimens were examined for extent of residual disease. Results: The tumors of 38 of 122 patients (31%) exhibited marked pathologic downstaging (no residual tumor or cancer confined to the rectal wall) after preoperative irradiation. Two features were associated with the likelihood of marked pathologic regression after preoperative irradiation: tumor proliferative activity and lesion size. When stratified by lesion size, marked tumor regression occurred most frequently in smaller tumors with high Ki-67, PCNA, and mitotic activity compared to larger tumors with lower Ki-67, PCNA, and mitotic activity. Intermediate downstaging rates were seen for small or large tumors with moderate Ki-67, PCNA, and mitotic activity. Conclusion: Tumor Ki-67, PCNA, and mitotic activity predicts the likelihood of response to irradiation, which may aid in formulating treatment policies for patients with rectal cancer

  3. Treatment Option Overview (Bladder Cancer)

    Science.gov (United States)

    ... Cancer Treatment Bladder Cancer Screening Research Bladder Cancer Treatment (PDQ®)–Patient Version General Information About Bladder Cancer ... Certain factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) depends on ...

  4. Transitional cell carcinoma of the bladder in childhood: radiological findings and differential diagnosis

    International Nuclear Information System (INIS)

    We present a case of transitional cell carcinoma of the bladder in an 11-year-old boy. The rarity of these tumors during childhood is pointed out. The radiological and ultrasonographic findings are described and the differential diagnosis is discussed with respect to other bladder tumors occurring in childhood. (Author) 11 refs

  5. Immunohistochemical study of the expression of cell cycle regulating proteins at different stages of bladder cancer

    DEFF Research Database (Denmark)

    Primdahl, Hanne; Maase, Hans von der; Sørensen, Flemming B.; Wolf, Hans; Ørntoft, Torben Falck

    2002-01-01

    PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue material consisted of bladder tumors from three groups of...

  6. Opportunities of radiological methods for examination in diagnostics of urinary bladder cancer

    OpenAIRE

    Chekhonatskaya M.L.; Popkov V.M.; Zuev V.V.; Glybochko P.V.; Ponukalin A.N.

    2011-01-01

    The research goal is the comparative analysis of Russian and foreign studies concerned the possibility of radiological methods of diagnostics of cancer of urinary bladder. The problem of early diagnostics of initial tumor and tumor recurrence, determination of stages of bladder cancer, its prognosis and outcome remains an actual one

  7. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Masaharu [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Koga, Fumitaka, E-mail: f-koga@cick.jp [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Yoshida, Soichiro [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Tamura, Tomoki [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Fujii, Yasuhisa [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Ito, Eisaku [Department of Pathology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan); Kihara, Kazunori [Department of Urology, Tokyo Medical and Dental University, Graduate School, Tokyo (Japan)

    2014-10-01

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  8. Significance of ERBB2 Overexpression in Therapeutic Resistance and Cancer-Specific Survival in Muscle-Invasive Bladder Cancer Patients Treated With Chemoradiation-Based Selective Bladder-Sparing Approach

    International Nuclear Information System (INIS)

    Purpose: To investigate the associations of ERBB 2 overexpression with chemoradiation therapy (CRT) resistance and cancer-specific survival (CSS) in muscle-invasive bladder cancer (MIBC) patients treated with the CRT-based bladder-sparing protocol. Methods and Materials: From 1997 to 2012, 201 patients with cT2-4aN0M0 bladder cancer were treated with CRT (40 Gy with concurrent cisplatin) following transurethral resection of bladder tumor (TURBT). Basically, patients with tumors that showed good CRT response and were amenable to segmental resection underwent partial cystectomy (PC) with pelvic lymph node dissection for bladder preservation; otherwise, radical cystectomy (RC) was recommended. Included in this study were 119 patients in whom TURBT specimens were available for immunohistochemical analysis of ERBB 2 expression. Following CRT, 30 and 65 patients underwent PC or RC, respectively; the remaining 24 patients did not undergo cystectomy. Tumors were defined as CRT-resistant when patients did not achieve complete response after CRT. Associations of ERBB 2 overexpression with CRT resistance and CSS were evaluated. Results: CRT resistance was observed clinically in 56% (67 of 119 patients) and pathologically (in cystectomy specimens) in 55% (52 of 95 patients). ERBB 2 overexpression was observed in 45 patients (38%). On multivariate analysis, ERBB 2 overexpression was an independent predictor for CRT resistance clinically (odds ratio, 3.6; P=.002) and pathologically (odds ratio, 2.9; P=.031). ERBB 2 overexpression was associated with shorter CSS (5-year CSS rates, 56% vs 87% for the ERBB 2 overexpression group vs the others; P=.001). ERBB 2 overexpression was also an independent risk factor for bladder cancer death at all time points of our bladder-sparing protocol (pre-CRT, post-CRT, and post-cystectomy). Conclusions: ERBB 2 overexpression appears relevant to CRT resistance and unfavorable CSS in MIBC patients treated with the CRT-based bladder

  9. A voxel-based multiscale model to simulate the radiation response of hypoxic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Espinoza, I., E-mail: iespinoza@fis.puc.cl [Institute of Physics, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany); Peschke, P. [Clinical Cooperation Unit Molecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany); Karger, C. P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120 (Germany)

    2015-01-15

    Purpose: In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan. Methods: A voxel-based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia-induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen-dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation-induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions. Results: The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the

  10. Sickle erythrocytes target cytotoxics to hypoxic tumor microvessels and potentiate a tumoricidal response.

    Directory of Open Access Journals (Sweden)

    David S Terman

    Full Text Available Resistance of hypoxic solid tumor niches to chemotherapy and radiotherapy remains a major scientific challenge that calls for conceptually new approaches. Here we exploit a hitherto unrecognized ability of sickled erythrocytes (SSRBCs but not normal RBCs (NLRBCs to selectively target hypoxic tumor vascular microenviroment and induce diffuse vaso-occlusion. Within minutes after injection SSRBCs, but not NLRBCs, home and adhere to hypoxic 4T1 tumor vasculature with hemoglobin saturation levels at or below 10% that are distributed over 70% of the tumor space. The bound SSRBCs thereupon form microaggregates that obstruct/occlude up to 88% of tumor microvessels. Importantly, SSRBCs, but not normal RBCs, combined with exogenous prooxidant zinc protoporphyrin (ZnPP induce a potent tumoricidal response via a mutual potentiating mechanism. In a clonogenic tumor cell survival assay, SSRBC surrogate hemin, along with H(2O(2 and ZnPP demonstrate a similar mutual potentiation and tumoricidal effect. In contrast to existing treatments directed only to the hypoxic tumor cell, the present approach targets the hypoxic tumor vascular environment and induces injury to both tumor microvessels and tumor cells using intrinsic SSRBC-derived oxidants and locally generated ROS. Thus, the SSRBC appears to be a potent new tool for treatment of hypoxic solid tumors, which are notable for their resistance to existing cancer treatments.

  11. Dynamics of tumor hypoxia in response to patupilone and ionizing radiation.

    Directory of Open Access Journals (Sweden)

    Katrin Orlowski

    Full Text Available Tumor hypoxia is one of the most important parameters that determines treatment sensitivity and is mainly due to insufficient tumor angiogenesis. However, the local oxygen concentration in a tumor can also be shifted in response to different treatment modalities such as cytotoxic agents or ionizing radiation. Thus, combined treatment modalities including microtubule stabilizing agents could create an additional challenge for an effective treatment response due to treatment-induced shifts in tumor oxygenation. Tumor hypoxia was probed over a prolonged observation period in response to treatment with different cytotoxic agents, using a non-invasive bioluminescent ODD-Luc reporter system, in which part of the oxygen-dependent degradation (ODD domain of HIF-1α is fused to luciferase. As demonstrated in vitro, this system not only detects hypoxia at an ambient oxygen concentration of 1% O(2, but also discriminates low oxygen concentrations in the range from 0.2 to 1% O(2. Treatment of A549 lung adenocarcinoma-derived tumor xenografts with the microtubule stabilizing agent patupilone resulted in a prolonged increase in tumor hypoxia, which could be used as marker for its antitumoral treatment response, while irradiation did not induce detectable changes in tumor hypoxia. Furthermore, despite patupilone-induced hypoxia, the potency of ionizing radiation (IR was not reduced as part of a concomitant or adjuvant combined treatment modality.

  12. Secondary specific immune response in vitro to MSV tumor cells.

    Science.gov (United States)

    Senik, A; Hebrero, F P; Levy, J P

    1975-12-15

    The interactions which occur between antigenic tumor cells and normal or immune lymphoid cells in a 3-day in vitro culture, have been studied with a murine sarcoma virus (MSV)-induced tumor. The 3H-thymidine incorporation of lymphoma cells growing in suspension, and the radioactive-chromium release of freshly sampled lymphoma cells regularly added to the culture, have been compared to determine the part played by immune lymphoid cells in cytolysis and cytostasis of the tumor-cell population. The cytolytic activity increases in the culture from day 0 to day 3. It is due, predominantly, to T-cells, and remains specific to antigens shared by MSV tumors and related lymphomas. This activity would be difficult to detect unless freshly sampled ascitic cells were used as targets, since the lymphoma cells spontaneously lose a part of their sensitivity to immune cytolysis during in vitro culture. The method used in the present experiments is a secondary chromium release test (SCRT), which measures the invitro secondary stimulation of cytotoxic T-lymphocytes (CTL) by tumor cells. In the absence of stimulatory cells, the CTL activity would have rapidly fallen in vitro. The cytostatic activity also increases during the 3 days in vitro, in parallel to the cytolytic activity: it is due to non-T-cells and remains mainly non-specific. The significance of these data for the interpretation of invitro demonstrated cell-mediated anti-tumor immune reactions is briefly discussed, as well as their relevance in the in vivo role of immune CTL. PMID:53210

  13. ROLE OF USG AND MDCT IN EVALUATION OF URINARY BLADDER MASS

    Directory of Open Access Journals (Sweden)

    Sunny

    2014-11-01

    Full Text Available Primary bladder neoplasms account for 2%–6% of all tumors, with bladder cancer ranked as the fourth most common malignancy (1 . Peak incidence is in the sixth and the seventh decades. Incidence is four times higher in men than in women. The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible (or elastic organ, the bladder sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra. (2 The bladder is readily identified by ultrasound, Computed Tomography, cystography, Magnetic Resonance Image (MRI and Cystoscopy, but Bladder ultrasound is noninvasive, readily accessible, and easy to use. It has been extensively investigated as a possible substitution for some of the more common invasive modalities used to evaluate the bladder

  14. Non-invasive in vivo imaging of early metabolic tumor response to therapies targeting choline metabolism.

    Science.gov (United States)

    Mignion, Lionel; Danhier, Pierre; Magat, Julie; Porporato, Paolo E; Masquelier, Julien; Gregoire, Vincent; Muccioli, Giulio G; Sonveaux, Pierre; Gallez, Bernard; Jordan, Bénédicte F

    2016-04-15

    The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1) H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H-89, indirect inhibitor sorafenib and down-regulation of choline-kinase α (ChKA) expression using specific short-hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti-ChKA shRNA significantly repressed tumor growth. The increase of apparent-diffusion-coefficient of water (ADCw) measured by DW-MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, (1) H-choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW-MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW-MRI combined to choline spectroscopy may provide a useful non-invasive marker for the early clinical assessment of tumor response to therapies targeting choline signaling. PMID:26595604

  15. Small Cell Carcinoma of the Urinary Bladder: KIT and PDGFRA Gene Mutations

    OpenAIRE

    Nuket Eliyakin; Hakan Postaci; Yasemin Baskin; Zafer Kozacioğlu

    2015-01-01

    Primary small cell carcinoma of the urinary bladder is very rare. A 72-year-old was admitted to our hospital because of hematuria and dysuria. Cystoscopy revealed a bladder full of multiple, solid and papillary tumors. Biopsies from the deep and papillary tumors were taken. Histologically, tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin, synaptophysin, neuron-specific enolase, CD56, CD117 and Ki67 (labeling 70%). The tumo...

  16. Molecular determinants of treatment response in human germ cell tumors

    NARCIS (Netherlands)

    F. Mayer; J.A. Stoop (Hans); G.L. Scheffer (George); R. Scheper; J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert); C. Bokemeyer

    2003-01-01

    textabstractPURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways ma

  17. The relationship between overactive bladder and sexual activity in women

    OpenAIRE

    Patel Ankur S.; O'Leary Margie L.; Stein Robert J.; Leng Wendy W.; Chancellor Michael B; Patel Subodh G.; Borello-France Diane

    2006-01-01

    PURPOSE: We assessed the relationships between bladder symptoms, demographic, and medical history variables and sexual dysfunction in women with overactive bladder (OAB) disorder. MATERIALS AND METHODS: Seventy-eight women diagnosed with OAB completed self-administered questionnaires related to overall heath status, bladder function, and sexual function. Data were compiled for questionnaire responses, and multivariate logistic regression analyses were performed to determine predictors of sexu...

  18. Tumor Interstitial Fluid Pressure as an Early-Response Marker for Anticancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Stephane Ferretti

    2009-09-01

    Full Text Available Solid tumors have a raised interstitial fluid pressure (IFP due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days or later (6 or 7 days lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P ≤ .005 correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  19. Whole-genome sequencing of a malignant granular cell tumor with metabolic response to pazopanib

    Science.gov (United States)

    Wei, Lei; Liu, Song; Conroy, Jeffrey; Wang, Jianmin; Papanicolau-Sengos, Antonios; Glenn, Sean T.; Murakami, Mitsuko; Liu, Lu; Hu, Qiang; Conroy, Jacob; Miles, Kiersten Marie; Nowak, David E.; Liu, Biao; Qin, Maochun; Bshara, Wiam; Omilian, Angela R.; Head, Karen; Bianchi, Michael; Burgher, Blake; Darlak, Christopher; Kane, John; Merzianu, Mihai; Cheney, Richard; Fabiano, Andrew; Salerno, Kilian; Talati, Chetasi; Khushalani, Nikhil I.; Trump, Donald L.; Johnson, Candace S.; Morrison, Carl D.

    2015-01-01

    Granular cell tumors are an uncommon soft tissue neoplasm. Malignant granular cell tumors comprise T transitions, particularly when immediately preceded by a 5′ G. A loss-of-function mutation was detected in a newly recognized tumor suppressor candidate, BRD7. No mutations were found in known targets of pazopanib. However, we identified a receptor tyrosine kinase pathway mutation in GFRA2 that warrants further evaluation. To the best of our knowledge, this is only the second reported case of a malignant granular cell tumor exhibiting a response to pazopanib, and the first whole-genome sequencing of this uncommon tumor type. The findings provide insight into the genetic basis of malignant granular cell tumors and identify potential targets for further investigation. PMID:27148567

  20. Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma

    DEFF Research Database (Denmark)

    Bonekamp, David; Mouridsen, Kim; Radbruch, Alexander;

    2016-01-01

    oxygenation appears to be worsened despite vascular normalization. Accordingly, hazards for both progression and death are found elevated in patients with a greater reduction of tumor metabolic rate of oxygen in response to bevacizumab and patients with higher intratumoral tumor metabolic rate of oxygen at......Antiantiogenic therapy with bevacizumab in recurrent glioblastoma is currently understood to both reduce microvascular density and to prune abnormal tumor microvessels. Microvascular pruning and the resulting vascular normalization are hypothesized to reduce tumor hypoxia and increase supply of...... systemic therapy to the tumor; however, the underlying pathophysiological changes and their timing after treatment initiation remain controversial. Here, we use a novel dynamic susceptibility contrast MRI-based method, which allows simultaneous assessment of tumor net oxygenation changes reflected by the...

  1. CIP2A protein expression in high-grade, high-stage bladder cancer

    International Nuclear Information System (INIS)

    Bladder cancer is one of the most common cancers in the United States. Numerous markers have been evaluated for suitability of bladder cancer detection and surveillance. However, few of them are acceptable as a routine tool. Therefore, there exists a continuing need for an assay that detects the presence of bladder cancer in humans. It would be advantageous to develop an assay with a protein that is associated with the development of bladder cancer. We have identified the cancerous inhibitor of PP2A (CIP2A) protein as a novel bladder cancer biomarker. In this study, Western blot analysis was used to assess the expression level of CIP2A protein in bladder cancer cell lines and bladder cancer patient tissues (n = 43). Our studies indicated CIP2A protein was abundantly expressed in bladder cancer cell lines but not in nontumor epithelial cell lines. Furthermore, CIP2A was specifically expressed in transitional cell carcinoma (TCC) of the bladder tumor tissues but not in adjacent nontumor bladder tissue. Our data showed that CIP2A protein detection in high-grade TCC tissues had a sensitivity of 65%, which is 3.4-fold higher than that seen in low-grade TCC tissues (19%). The level of CIP2A protein expression increased with the stage of disease (12%, 27%, 67%, and 100% for pTa, pT1, pT2, and pT3 tumor, respectively). In conclusion, our studies suggest that CIP2A protein is specifically expressed in human bladder tumors. CIP2A is preferentially expressed in high-grade and high-stage TCC tumors, which are high-risk and invasive tumors. Our studies reported here support the role of CIP2A in bladder cancer progression and its usefulness for the surveillance of recurrence or progression of human bladder cancer

  2. A study of an effective sunitinib–chemotherapeutic combination regimen for bladder cancer treatment using a mouse model

    Directory of Open Access Journals (Sweden)

    Dah-Shyong Yu

    2014-06-01

    Conclusion: Combination of the tyrosine kinase receptor inhibitor sunitinib with gemcitabine chemotherapy synergistically enhances tumor cytotoxicity and may provide a new treatment modality for advanced bladder cancer.

  3. Tumor and normal tissue responses to fractioned non-uniform dose delivery

    International Nuclear Information System (INIS)

    The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, γ, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters α and β. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs

  4. Stages of Bladder Cancer

    Science.gov (United States)

    ... red in color). Frequent urination. Pain during urination. Lower back pain. Tests that examine the urine and bladder are used to help detect (find) and diagnose bladder cancer. The following tests and ... left. Treatment given after surgery, to lower the risk that the cancer will come back, ...

  5. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has...

  6. Bladder pain syndrome

    DEFF Research Database (Denmark)

    Hanno, Philip; Nordling, Jørgen; Fall, Magnus

    2011-01-01

    Bladder pain syndrome is a deceptively intricate symptom complex that is diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom. It is a diagnosis of exclusion in a patient who has ex...

  7. Combined-modality treatment and organ preservation in bladder cancer. Do molecular markers predict outcome?

    International Nuclear Information System (INIS)

    Purpose: in invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ-sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed. Patients and methods: the apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis. Results: the median AI for all patients was 1.5% (range 0.2-7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder. Conclusion: The indices of pretreatment apoptosis and Ki-67 predict a

  8. Plasticity of gamma delta T cells: impact on the anti-tumor response

    Directory of Open Access Journals (Sweden)

    Virginie eLafont

    2014-12-01

    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  9. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt; Rudkjær, Lise; Ørntoft, Torben Falck; Wewer, Ulla M.

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined by...... could be detected in the urine by Western blotting; ADAM12 was present in higher levels in the urine from patients with bladder cancer compared with urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined, the level of ADAM12 in the...

  10. Role of VEGF in the growth and metastasis of a murine bladder carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Feng; WU Jihong; TIAN Yuhua; CHEN Xiafang; HU Honghui; WU Wensen; LI Chuanyuan; HUANG Qian

    2003-01-01

    Bladder transitional cell carcinoma is the most common form of carcinoma in the urinary system. Although overexpression of VEGF has been identified in tissue, serum, and urine of patients with bladder cancer, the role of VEGF in transitional cell carcinoma of the bladder has not been clearly elucidated. Here, we dissected the effect of VEGF during bladder tumor growth and progression by modifying a BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine) induced mouse bladder transitional cell carcinoma cell line BTT-T739 by stable transfection of antisense VEGF121 cDNA. The transfection resulted in more than 80% reduction in VEGF production. The growth of the transduced tumor cells in vitro was not affected, however, these cells formed small or no tumors in vivo. Even in the tumors formed, there were mini- mal vascularization, extensive necrosis and longer latency compared to those formed by parental cells. The permeability of tumor vasculature and metastatic tumor growth were also significantly suppressed in antisense VEGF cDNA trans- fected cells. In addition, the transfer of anti-angiogenic gene in a combination of sFlk-1 and ExTek with electroporation can suppress the tumor growth efficiently. Taken together, these results demonstrated that VEGF plays an important role in bladder tumor angiogenesis and angiogenesis plays an important role in bladder tumor growth and metastasis.

  11. Inflammatory and Tumor Stimulating Responses after Laparoscopic Sigmoidectomy

    OpenAIRE

    Kim, Jin Soo; Hur, Hyuk; Min, Byung Soh; Lee, Kang Young; Chung, Hyun Cheol; Kim, Nam Kyu

    2011-01-01

    Purpose Laparoscopic colectomy has clinical benefits such as short hospital stay, less postoperative pain, and early return of bowel function. However, objective evidence of its immunologic and oncologic benefits is scarce. We compared functional recovery after open versus laparoscopic sigmoidectomy and investigated the effect of open versus laparoscopic surgery on acute inflammation as well as tumor stimulation. Materials and Methods A total of 57 patients who were diagnosed with sigmoid col...

  12. A study of image-guided radiotherapy of bladder cancer based on lipiodol injection in the bladder wall

    International Nuclear Information System (INIS)

    Purpose. We have tested a procedure of focal injection of the contrast medium Lipiodol as a fiducial marker for image-guided boost of the tumor in bladder cancer radiotherapy (RT). In this study, we have evaluated the feasibility and the safety of the method as well as the inter- and intra-fraction shift of the bladder tumor. Materials and methods. Five patients with muscle invasive urinary bladder cancer were included in the study. Lipiodol was injected during flexible cystoscopy into the submucosa of the bladder wall at the periphery of the tumor or the post resection tumor-bed. Cone-beam CT (CBCT) scans were acquired daily throughout the course of RT. Results. Lipiodol demarcation of the bladder tumor was feasible and safe with only a minimum of side effects related to the procedure. The Lipiodol spots were visible on CT and CBCT scans for the duration of the RT course. More than half of all the treatment fractions required a geometric shift of 5 mm or more to match on the Lipiodol spots. The mean intra-fraction shift (3D) of the tumor was 3 mm, largest in the anterior-posterior and cranial-caudal directions. Conclusion. This study demonstrates that Lipiodol can be injected into the bladder mucosa and subsequently visualized on CT and CBCT as a fiducial marker. The relatively large inter-fraction shifts in the positions of Lipiodol spots compared to the intra-fraction movement indicates that image-guided RT based on radio-opaque markers is important for RT of the bladder cancer tumor.

  13. Dynamics of liquid sloshing in upright and inverted bladdered tanks

    Science.gov (United States)

    Dodge, F. T.; Kana, D. D.

    A system identification methodology was used to examine the dynamics of liquid sloshing in the upright and inverted bladdered hydrazine tanks of the Tracking and Data Relay Satellite, (TDRS) and to evaluate the effects of bladder stiffness on the sloshing parameters. Mechanical models of the two systems were developed using the numerical values derived from static stability tests and from slosh frequency response tests of a full-size model tank fitted with a prototype bladder. For the upright tank (liquid below the bladder) a modified conventional pendulum was used. In the inverted tank (liquid above the bladder) where sloshing is unconventional due to the highly nonsymmetrical orientation of the liquid held by the bladder, a mechanical model using an inverted pendulum which is able to undergo small oscillations as well as large reorientations was necessary. Both thrusting and low-gravity conditions are considered.

  14. Imaging of Gastrointestinal Stromal Tumors: From Diagnosis to Evaluation of Therapeutic Response.

    Science.gov (United States)

    Vernuccio, Federica; Taibbi, Adele; Picone, Dario; LA Grutta, Ludovico; Midiri, Massimo; Lagalla, Roberto; Lo Re, Giuseppe; Bartolotta, Tommaso Vincenzo

    2016-06-01

    Once considered an obscure tumor entity with poor prognosis, gastrointestinal stromal tumors (GISTs) are nowadays recognized as the most common mesenchymal tumors of the alimentary tract. GISTs differ from other mesenchymal neoplasms at pathology since 90% of them exhibit strong immunohistochemical staining for KIT, a tyrosinase kinase growth factor receptor. In the early 2000s, the ability of imatinib mesylate, a tyrosine kinase inhibitor, to inhibit KIT established a new paradigm for cancer treatment. A reduction in lesion size may not be observed or may appear many months after therapy; thus, tumor response criteria alternative to the Response Evaluation Criteria in Solid Tumors were developed. This review highlights the role of imaging in the detection, characterization, preoperative staging, postoperative assessment, therapy-response evaluation and treatment-related toxicities. All this information is crucial in optimizing patient management. Contrast-enhanced computed tomography is the most commonly used modality for staging the disease and assessing treatment response, whereas positron-emission tomography adds valuable functional information. Magnetic resonance imaging (MRI) may also be useful, especially in ano-rectal GISTs. Diffusion-weighted MRI may provide promising indicators of tumor response to targeted molecular therapy. Radiologists and oncologists should be aware of all these issues related to GISTs, since multidisciplinary teams gathering different expertise are usually needed to properly treat patients with GISTs. PMID:27272772

  15. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Hoogsteen, Ilse J., E-mail: i.hoogsteen@rther.umcn.nl [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Marres, Henri A.M.; Hoogen, Franciscus J.A. van den [Department of Otorhinolaryngology/Head-Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Rijken, Paul F.J.W.; Lok, Jasper; Bussink, Johan; Kaanders, Johannes H.A.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)

    2012-11-01

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  16. Expression of EGFR Under Tumor Hypoxia: Identification of a Subpopulation of Tumor Cells Responsible for Aggressiveness and Treatment Resistance

    International Nuclear Information System (INIS)

    Purpose: Overexpression of epidermal growth factor receptor (EGFR) and tumor hypoxia have been shown to correlate with worse outcome in several types of cancer including head-and-neck squamous cell carcinoma. Little is known about the combination and possible interactions between the two phenomena. Methods and Materials: In this study, 45 cases of histologically confirmed squamous cell carcinomas of the head and neck were analyzed. All patients received intravenous infusions of the exogenous hypoxia marker pimonidazole prior to biopsy. Presence of EGFR, pimonidazole binding, and colocalization between EGFR and tumor hypoxia were examined using immunohistochemistry. Results: Of all biopsies examined, respectively, 91% and 60% demonstrated EGFR- and pimonidazole-positive areas. A weak but significant association was found between the hypoxic fractions of pimonidazole (HFpimo) and EGFR fractions (F-EGFR) and between F-EGFR and relative vascular area. Various degrees of colocalization between hypoxia and EGFR were found, increasing with distance from the vasculature. A high fraction of EGFR was correlated with better disease-free and metastasis-free survival, whereas a high degree of colocalization correlated with poor outcome. Conclusions: Colocalization of hypoxia and EGFR was demonstrated in head-and-neck squamous cell carcinomas, predominantly at longer distances from vessels. A large amount of colocalization was associated with poor outcome, which points to a survival advantage of hypoxic cells that are also able to express EGFR. This subpopulation of tumor cells might be indicative of tumor aggressiveness and be partly responsible for treatment resistance.

  17. The impact of ranitidine on monocyte responses in the context of solid tumors.

    Science.gov (United States)

    Vila-Leahey, Ava; Rogers, Dakota; Marshall, Jean S

    2016-03-01

    Monocytes and myeloid derived suppressor cells (MDSC) have been implicated on the regulation of tumor growth. Histamine is also important for regulating MDSC responses. Oral administration of the H2 receptor antagonist ranitidine can inhibit breast tumor growth and metastasis. In the current study, we examined the impact of oral ranitidine treatment, at a clinically relevant dose, on multiple murine tumor models. The impact of ranitidine on monocyte responses and the role of CCR2 in ranitidine-induced tumor growth inhibition were also investigated. Oral ranitidine treatment did not reduce tumor growth in the B16-F10 melanoma, LLC1 lung cancer and EL4 thymoma models. However, it consistently reduced E0771 primary tumor growth and metastasis in the 4T1 model. Ranitidine had no impact on E0771 tumor growth in mice deficient in CCR2, where monocyte recruitment to tumors was limited. Analysis of splenic monocytes also revealed an elevated ratio of H2 versus H1 expression from tumor-bearing compared with naïve mice. More detailed examination of the role of ranitidine on monocyte development demonstrated a decrease in monocyte progenitor cells following ranitidine treatment. Taken together, these results reveal that H2 signaling may be a novel target to alter the monocyte population in breast tumor models, and that targeting H2 on monocytes via oral ranitidine treatment impacts effective tumor immunity. Ranitidine is widely used for control of gastrointestinal disorders. The potential role of ranitidine as an adjunct to immunotherapies for breast cancer and the potential impact of H2 antagonists on breast cancer outcomes should be considered. PMID:26863636

  18. Enhancement of tumor response by MEK inhibitor in murine HCa-I tumors

    International Nuclear Information System (INIS)

    Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protein kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Murine hepatocarcinoma, HCa-l is known to be highly radioresistant with a TCD50 (radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5-8 mm. HCa-l, were treated with PD98059 (intratumoral injection of 0.16 μg in 50 μl). Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed up regulation of p53, p21WAF1/CIP1 and Bcl-Xs in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-XL, Bax and BCI-2 were changed to a lesser extent. The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment

  19. Partial cystectomy in a 76 year old patient suffering from small cell carcinoma of the urinary bladder

    OpenAIRE

    Starownik, Radosław; Korolczuk, Agnieszka; Bar, Krzysztof; Płaza, Paweł; Kiś, Jacek; Muc, Kamil; Bar, Marek

    2013-01-01

    Small cell carcinomas of the urinary bladder originating from the neuroendocrine cells are extremely rare. We present a case of a 76–year–old patient with small cell carcinoma of the urinary bladder. The patient had hematuria and cystoscopy revealed a tumor located in a urinary bladder diverticulum. Partial resection of the bladder wall with diverticulectomy was performed. Microscopic examination established the diagnosis of neuroendocrine carcinoma, which was confirmed by immunohistochemistr...

  20. Cathepsin-D And Tnf-α in Bladder Cancer

    Directory of Open Access Journals (Sweden)

    T. Salman

    1996-01-01

    Full Text Available In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones, serum tumor necrosis factor alpha (TNF-α and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-α showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzia ova or lymph node involvement.

  1. Biphasic modeling of brain tumor biomechanics and response to radiation treatment.

    Science.gov (United States)

    Angeli, Stelios; Stylianopoulos, Triantafyllos

    2016-06-14

    Biomechanical forces are central in tumor progression and response to treatment. This becomes more important in brain cancers where tumors are surrounded by tissues with different mechanical properties. Existing mathematical models ignore direct mechanical interactions of the tumor with the normal brain. Here, we developed a clinically relevant model, which predicts tumor growth accounting directly for mechanical interactions. A three-dimensional model of the gray and white matter and the cerebrospinal fluid was constructed from magnetic resonance images of a normal brain. Subsequently, a biphasic tissue growth theory for an initial tumor seed was employed, incorporating the effects of radiotherapy. Additionally, three different sets of brain tissue properties taken from the literature were used to investigate their effect on tumor growth. Results show the evolution of solid stress and interstitial fluid pressure within the tumor and the normal brain. Heterogeneous distribution of the solid stress exerted on the tumor resulted in a 35% spatial variation in cancer cell proliferation. Interestingly, the model predicted that distant from the tumor, normal tissues still undergo significant deformations while it was found that intratumoral fluid pressure is elevated. Our predictions relate to clinical symptoms of brain cancers and present useful tools for therapy planning. PMID:27086116

  2. Intramural leiomyomas of the bladder in asymptomatic men

    Directory of Open Access Journals (Sweden)

    Roberto I. Lopes

    2003-06-01

    Full Text Available Bladder leiomyomas are rare benign mesenchymal tumors, which account for less than 0.43% of all bladder tumors with approximately 200 cases described in the literature. These tumors may be classified into 3 different locations: endovesical, intramural and extravesical. Endovesical is the most common form, accounting for 63-86% of the cases, while intramural occurs in 3-7% and extravesical in 11-30%. The intramural form, especially small tumors, may not produce symptoms hardening detection. We report two cases of intramural bladder leiomyomas in asymptomatic men observed incidentally by transabdominal ultrasonography during the follow-up of benign prostatic hyperplasia. We discuss the diagnosis and management of these lesions.

  3. X-ray responses of human colon tumor cells grown in artificial capillary culture

    International Nuclear Information System (INIS)

    Clone A human colon adenocarcinoma cells were grown in three-dimensional artificial capillary culture (ACC) to determine responses of capillaries treated 3 weeks after tumor cell inoculation with a specific, easily quantifiable cytotoxic agent, ionizing radiation. Changes in extracapillary space (ECS) fluid concentrations of lactate dehydrogenase (LDH) and aspartate aminotransferase (GOT) and the utilization of glucose in circulating medium were monitored after a supralethal radiation dose (90 Gy) of X-rays. Immediately after irradiation, increased levels of LDH and GOT were found that reached maximum levels about four to five times those found in nonirradiated control capillaries at 10-13 days post irradiation and then declined. Patterns of enzyme production appeared to correlate with the numbers of nonviable tumor cells collected from the ECS of the artificial capillaries. In contrast, glucose utilization showed little correlation with either enzyme concentration or dead cell production. In other studies, tumor cells were removed from unirradiated capillaries by trypsinization and used to obtain complete survival curves after graded doses of X-radiation. The dose-response curves obtained indicate that clone A colon tumor cells grown in ACC show a marked decrease in their ability to accumulate sublethal radiation injury as compared to responses of these cells growing exponentially in asynchronous monolayer cultures, to synchronized mid-G1 tumor cells, or to tumor cells in stationary growth phase. These data suggest that ACC is a potentially useful model to study the effects of cytotoxic agents on human tumor cells

  4. β-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses.

    Science.gov (United States)

    Ning, Yongling; Xu, Dongqin; Zhang, Xiaohang; Bai, Yu; Ding, Jun; Feng, Tongbao; Wang, Shizhong; Xu, Ning; Qian, Keqing; Wang, Yong; Qi, Chunjian

    2016-06-01

    Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of β-glucan on TEDCs and found that β-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy and suggesting its potential clinical benefit. β-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses. PMID:26773960

  5. Metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice.

    Science.gov (United States)

    Montales, Maria Theresa E; Melnyk, Stepan B; Liu, Shi J; Simmen, Frank A; Liu, Y Lucy; Simmen, Rosalia C M

    2016-09-01

    The emerging links between breast cancer and metabolic dysfunctions brought forth by the obesity pandemic predict a disproportionate early disease onset in successive generations. Moreover, sensitivity to chemotherapeutic agents may be influenced by the patient's metabolic status that affects the disease outcome. Maternal metabolic stress as a determinant of drug response in progeny is not well defined. Here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus-Wnt1 transgenic offspring exposed to a metabolically compromised environment imposed by maternal high-fat diet. Control progeny were from dams consuming diets with regular fat content. Maternal high-fat diet exposure increased tumor incidence and reduced tumor latency but did not affect tumor volume response to doxorubicin, compared with control diet exposure. However, doxorubicin-treated tumors from high-fat-diet-exposed offspring demonstrated higher proliferation status (Ki-67), mammary stem cell-associated gene expression (Notch1, Aldh1) and basal stem cell-like (CD29(hi)CD24(+)) epithelial subpopulation frequencies, than tumors from control diet progeny. Notably, all epithelial subpopulations (CD29(hi)CD24(+), CD29(lo)CD24(+), CD29(hi)CD24(+)Thy1(+)) in tumors from high-fat-diet-exposed offspring were refractory to doxorubicin. Further, sera from high-fat-diet-exposed offspring promoted sphere formation of mouse mammary tumor epithelial cells and of human MCF7 cells. Untargeted metabolomics analyses identified higher levels of kynurenine and 2-hydroxyglutarate in plasma of high-fat diet than control diet offspring. Kynurenine/doxorubicin co-treatment of MCF7 cells enhanced the ability to form mammosphere and decreased apoptosis, relative to doxorubicin-only-treated cells. Maternal metabolic dysfunctions during pregnancy and lactation may be targeted to reduce breast cancer risk and improve early drug response in progeny, and may inform clinical management of disease

  6. Preliminary results of a phase III trial of spontaneous animal tumors to heat and/or radiation: early normal tissue response and tumor volume influence on initial response

    International Nuclear Information System (INIS)

    A Phase III randomized trial was initiated to test the relative efficacies of heat alone, radiation alone and heat plus radiation using spontaneous malignancies in pet animals. Heat alone was inferior to the other two treatment arms as demonstrated by a significantly higher non-response rate and shorter response duration. The ratio of complete response rates (CR) for heat plus radiation to radiation alone or the thermal relative risk (TRR) was greater for tumors > 10 cm3 as compared to those 3 (TRR = 4.8 and 1.4, respectively). The overall TRR for complete responses was 2.3. The CR data for the combined therapy arm indicate at least an additive effect between heat and radiation for small tumors but most likely a synergistic effect in the larger tumor gap. Based on the data currently available, no significant difference in response duration is observed between the two radiation arms, although a nonsignificant advantage to the combination therapy exists. Normal tissue effects were evaluated by incidence of full moist desquamation within the irradiated volume, late fibrosis and bone necrosis. Since the radiation skin dose depended upon the technique being used it was possible to estimate the dose to achieve moist desquamation in 50% of the animals (DD50) by a logistic regression model as being 3728 -/+ 344 rad for radiation alone. Significant lowering of the DD50 was not observed for the addition of heat to radiation. Low patient numbers where intact skin was heated prevented an accurate analysis of the effect, however

  7. Treatment results of radiation therapy for muscle-invasive bladder cancer

    Energy Technology Data Exchange (ETDEWEB)

    Langsenlehner, Tanja; Doeller, Carmen; Stranzl-Lawatsch, Heidi; Kapp, Karin S. [Univ. Clinic of Therapeutic Radiology and Oncology, Medical Univ. of Graz (Austria); Quehenberger, Franz [Inst. for Medical Informatics, Statistics and Documentation, Medical Univ. of Graz (Austria); Langsenlehner, Uwe [Internal Outpatient Dept., Steiermaerkische GKK, Graz (Austria); Pummer, Karl [Dept. of Urology, Medical Univ. of Graz (Austria)

    2010-04-15

    Purpose: To assess local control and survival rates in patients with muscle-invasive bladder cancer treated with external-beam radiotherapy and to investigate prognostic factors. Patients and methods: Between 1997 and 2007, 75 patients (male, n = 58; female, n = 17, median age, 74.2 years) with localized transitional cell carcinoma of the bladder (T2, n = 34; T3, n = 32; T4, n = 9) not suitable for radical surgery due to advanced age, comorbidity or inoperability underwent external-beam radiotherapy without simultaneous chemotherapy at the University Clinic of Therapeutic Radiology and Oncology, Medical University of Graz, Austria. A conformal four-field technique was used in all patients to treat the tumor and regional lymph nodes with single daily fractions of 1.8-2 Gy to a total dose of 50-50.4 Gy, followed by a cone-down to encompass the empty bladder which was boosted to 70-70.4 Gy. All patients had undergone transurethral tumor resection prior to radiotherapy which was macroscopically incomplete in 62 patients. Results: Complete response was achieved in 65% of patients. Actuarial 3-year local control and metastases-free survival rates were 52.5% and 63.7%, 3-year local recurrence-free survival rate in complete responders was 71%. In univariate analysis, hydronephrosis, lymph vessel invasion, and macroscopic residual tumor were significantly predictive of disease progression. Hydronephrosis and lymph vessel invasion were also associated with a higher risk of local recurrence. The actuarial 3-year progression-free and overall survival rates were 40.1% and 56.9%, respectively. Conclusion: Radiotherapy is an effective treatment option in terms of local control and survival even in elderly patients with locally advanced bladder cancer not suitable for cystectomy. (orig.)

  8. A kinetic model of tumor growth and its radiation response with an application to Gamma Knife stereotactic radiosurgery

    CERN Document Server

    Watanabe, Yoichi; Leder, Kevin Z; Hui, Susanta K

    2015-01-01

    We developed a mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. We made several key assumptions of the model. Tumor volume is composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time, Td) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, theta. Upon irradiation the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time, Tcl. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumor and metastatic brain tumors of five patients who were treated by Gamma Knife stereotactic radiosurgery (GKSRS). By selecting appropriate model parameters, we showed the temporal variation of the tumors for both th...

  9. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  10. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    International Nuclear Information System (INIS)

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  11. Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Zhongwei Qiao

    Full Text Available This study utilized magnetic resonance imaging (MRI to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL-1α, IL-6 and tumor necrosis factor (TNFα levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

  12. Hemodynamic response imaging: a potential tool for the assessment of angiogenesis in brain tumors.

    Directory of Open Access Journals (Sweden)

    Dafna Ben Bashat

    Full Text Available Blood oxygenation level dependence (BOLD imaging under either hypercapnia or hyperoxia has been used to study neuronal activation and for assessment of various brain pathologies. We evaluated the benefit of a combined protocol of BOLD imaging during both hyperoxic and hypercapnic challenges (termed hemodynamic response imaging (HRI. Nineteen healthy controls and seven patients with primary brain tumors were included: six with glioblastoma (two newly diagnosed and four with recurrent tumors and one with atypical-meningioma. Maps of percent signal intensity changes (ΔS during hyperoxia (carbogen; 95%O2+5%CO2 and hypercapnia (95%air+5%CO2 challenges and vascular reactivity mismatch maps (VRM; voxels that responded to carbogen with reduced/absent response to CO2 were calculated. VRM values were measured in white matter (WM and gray matter (GM areas of healthy subjects and used as threshold values in patients. Significantly higher response to carbogen was detected in healthy subjects, compared to hypercapnia, with a GM/WM ratio of 3.8 during both challenges. In patients with newly diagnosed/treatment-naive tumors (n = 3, increased response to carbogen was detected with substantially increased VRM response (compared to threshold values within and around the tumors. In patients with recurrent tumors, reduced/absent response during both challenges was demonstrated. An additional finding in 2 of 4 patients with recurrent glioblastoma was a negative response during carbogen, distant from tumor location, which may indicate steal effect. In conclusion, the HRI method enables the assessment of blood vessel functionality and reactivity. Reference values from healthy subjects are presented and preliminary results demonstrate the potential of this method to complement perfusion imaging for the detection and follow up of angiogenesis in patients with brain tumors.

  13. Hedgehog Signaling Regulates Bladder Cancer Growth And Tumorigenicity

    OpenAIRE

    Fei, Dennis Liang; Sanchez-Mejias, Avencia; Wang, Zhiqiang; Flaveny, Colin; Long, Jun; Singh, Samer; Rodriguez-Blanco, Jezabel; Tokhunts, Robert; Giambelli, Camilla; Briegel, Karoline J.; Schulz, Wolfgang A; Gandolfi, A. Jay; Karagas, Margaret; Zimmers, Teresa A.; Jorda, Merce

    2012-01-01

    The role of HEDGEHOG (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We...

  14. CADrx for GBM Brain Tumors: Predicting Treatment Response from Changes in Diffusion-Weighted MRI

    Directory of Open Access Journals (Sweden)

    Matthew S. Brown

    2009-11-01

    Full Text Available The goal of this study was to develop a computer-aided therapeutic response (CADrx system for early prediction of drug treatment response for glioblastoma multiforme (GBM brain tumors with diffusion weighted (DW MR images. In conventional Macdonald assessment, tumor response is assessed nine weeks or more post-treatment. However, we will investigate the ability of DW-MRI to assess response earlier, at five weeks post treatment. The apparent diffusion coefficient (ADC map, calculated from DW images, has been shown to reveal changes in the tumor’s microenvironment preceding morphologic tumor changes. ADC values in treated brain tumors could theoretically both increase due to the cell kill (and thus reduced cell density and decrease due to inhibition of edema. In this study, we investigated the effectiveness of features that quantify changes from pre- and post-treatment tumor ADC histograms to detect treatment response. There are three parts to this study: first, tumor regions were segmented on T1w contrast enhanced images by Otsu’s thresholding method, and mapped from T1w images onto ADC images by a 3D region of interest (ROI mapping tool using DICOM header information; second, ADC histograms of the tumor region were extracted from both pre- and five weeks post-treatment scans, and fitted by a two-component Gaussian mixture model (GMM. The GMM features as well as standard histogram-based features were extracted. Finally, supervised machine learning techniques were applied for classification of responders or non-responders. The approach was evaluated with a dataset of 85 patients with GBM under chemotherapy, in which 39 responded and 46 did not, based on tumor volume reduction. We compared adaBoost, random forest and support vector machine classification algorithms, using ten-fold cross validation, resulting in the best accuracy of 69.41% and the corresponding area under the curve (Az of 0.70.

  15. FDG-PET during Therapy of Head and Neck Carcinomas. Prediction of tumor response and associations to tumor cell properties

    International Nuclear Information System (INIS)

    Introduction: Correlations between FDG uptake to single tumor properties, such as tumor grade, tumor cell proliferation or DNA ploidy have failed. Association between FDG metabolism during cytotoxic therapy, treatment outcome and tumor cell properties were evaluated in a prospective study of 47 patients with locally advanced head neck carcinomas (HNSCC) receiving radical treatment, radiotherapy with or without neoadjuvant cisplatinum-based chemotherapy. Methods: Repeated FDG PET scans with evaluation of metabolic rate of FDG (MR FDG) before and early during, either radiotherapy or initial chemotherapy. Fine needle aspiration of palpable node metastasis was performed in 31 patients immediately after each PET scan for analysis of S-phase (SPF), and DNA ploidy (analyzed by FCM and Image Cytometry; ICM). The associations between MR FDG and therapy outcome, and MR FDG and ploidy and s-phase were evaluated. We also studied changes in these properties during therapy. Results: Early changes in MR FDG were associated to treatment outcome, both survival and locoregional control. MR FDG below the median value during therapy was associated to a significantly better outcome, compared to MR FDG above the median value. This regards both 5 year-survival (72 % and 35% resp., p 0.0042) and locoregional control (96% and 55% resp., p 0.002). Analysis of DNA ploidy revealed differences depending on analyses used. ICM identified primarily more non-diploid tumors than FCM did, as well as more persisting non-diploid clones during treatment. No significant association to treatment outcome depending on DNA ploidy or SPF was seen.There was neither any significant association between DNA ploidy nor SPF to MR FDG. Conclusions: MR FDG during therapy was associated to therapy outcome, and thus enabling in vivo monitoring of metabolic response. Ploidy and SPF was not associated to FDG-metabolism

  16. Effect of hyperglycemia on the tumor response to irradiation given alone or in combination with hyperthermia

    Energy Technology Data Exchange (ETDEWEB)

    Urano, M.; Todoroki, T.; Kahn, J.; Okunieff, P.

    1987-09-01

    The effect of hyperglycemia (elevated blood glucose level) on the response of a murine tumor to irradiation given alone or in combination with hyperthermia was studied. Tumors were early generation isotransplants of a spontaneous C3H/Sed mouse fibrosarcoma, FSa-II. Single-cell suspensions were transplanted into the foot, and irradiation was given when each tumor reached an average diameter of 7 mm. Following irradiation, the tumor growth time to reach 1000 mm3 was studied and the dose-response curve between the tumor growth time and radiation dose was fitted. Preadministration of glucose increased the size of the hypoxic and chronically hypoxic cell fractions without altering the slope of the dose-response curve where the chronically hypoxic cell fraction is determined as the fraction of cells which were not oxygenated under hyperbaric oxygen conditions. Hyperthermia given prior to irradiation enhanced the tumor response to irradiation, but simultaneously increased the size of the hypoxic and chronically hypoxic cell fractions. Similar results were observed following hyperthermia given after irradiation. When hyperthermia at 43.5 degrees C was given 24 h before irradiation, the size of the hypoxic cell fraction increased with increasing treatment time, while a substantial decrease in the chronically hypoxic cell fraction was observed. Administration of glucose 60 min before hyperthermia further increased the size of the hypoxic cell fraction. Possible mechanisms explaining why glucose administration increases the hypoxic cell fractions are discussed.

  17. Contrast-enhanced MR imaging monitoring of acute tumor response to chemotherapy

    International Nuclear Information System (INIS)

    Treatment responses of human malignant melanomas were monitored at millimeter resolution in athymic mice by injecting a new polymeric contrast agent, Gd-DTPA-dextran (0.1 mmol Gd/kg, intravenously). Proton MR imaging (0.35 T, spin-echo, repetition time = 0.5 second, echo time = 50 msec) was performed 30 hours after administering diphtheria toxin. Pre-contrast medium images revealed only homogeneous intermediate-intensity tumor masses. Post-contrast medium images of untreated (viable) tumors demonstrated 32% enhancement throughout the entire mass. Post-contrast medium images of toxin-treated tumors revealed marked enhancement (65%) of the histologically viable outer rims, lesser enhancement (38%) of heavily damaged subregions, and no enhancement of dead tumor. These acute, contrast medium-enhanced MR images accurately identified tumor subregions that survived for longer than one week

  18. A new marker for normal tissue and tumor responses to irradiation in vivo

    International Nuclear Information System (INIS)

    Impairment of normal tissue is one of the major concerns associated with radiotherapy of tumors. Side effects such as enterobrosia and cognitive problems are reported after exposure to radiation during and after cancer therapy. This study evaluated the ability of 14C-Thymidine for detecting the early effects of irradiation on tumor, gut and skin proliferation-rate. To measured 14C-Thymidine uptake, mice were intravenously injected with tracers. The linear energy transfer (LET) and dose-related decrease in 14C-Thymidine in NFSa tumor were observed 12 hours after carbon-beam irradiation. Furthermore, the reduction in 14C-Thymidine uptake at 12 hours was correlated with tumor-volume at 14 days after irradiation. These findings demonstrated that the thymidine uptake could be an appropriate marker for investigating tumor proliferation-rate after radiotherapy of malignant diseases. Thymidine uptake could predict for or allow for rapid monitoring of response to radiotherapy. (author)

  19. In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

    International Nuclear Information System (INIS)

    Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer. Key words: Single-walled carbon nanotubes; Bladder cancer; Drug vehicle; THP; Intravesical chemotherapy

  20. A Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy

    International Nuclear Information System (INIS)

    Purpose: To assess the long term efficacy of neoadjuvant MCV (Methotrexate, Cisplatin, Vinblastine) chemotherapy in patients with muscle invading bladder cancer treated by combined modality therapy with selection for consolidation by either cystectomy or Cisplatin and radiation (XRT) based on initial response. Patients and Methods: From 1990 through 1993, 126 patients (median age 68 years, range39 to 83 years) with clinical stage T2-T4aNXM0 bladder cancer were randomized following a thorough transurethral resection (TURBT), if possible, to receive (Arm 1, N=62) or not (Arm 2, N=64) 2 cycles of MCV prior to 39.6Gy pelvic irradiation with concurrent Cisplatin (100mg/M2) 2 courses, 3 weeks apart. Tumor response was scored as a clinical CR when the tumor-site biopsy and urine cytology were negative. The CR patients were treated with consolidation of an additional 25.2Gy to a total of 64.8Gy with 1 additional cycle of Cisplatin. Those with less than a CR were advised prompt cystectomy as were those with a subsequent invasive recurrence. The median follow up of surviving patients is 44 months. Results: 72% of patients completed the protocol with no or minor deviations; 62% on Arm 1 and 82% on Arm 2. The actuarial 5 year overall survival is 47%; 42% in Arm 1 and 50% in Arm 2. 40% of the patients had evidence of distant metastases at 5 years; 35% in Arm 1 and 43% in Arm 2. The 5 year survival with a functioning bladder is 36%, 32% in Arm 1, 39% in Arm 2. Among the 72 CR patients (60% CR in Arm 1 and 55% CR in Arm 2) 13% have had evidence of an invasive tumor relapse at 5 years. Six patients died during treatment; 5 in Arm 1, 1 in Arm 2. No patient required a cystectomy for treatment-related bladder morbidity. Conclusions: Two cycles of MCV neoadjuvant chemotherapy was not shown to provide an improved rate of CR to induction therapy or freedom from metastatic disease, or in five year overall survival. This absence of benefit in any of these endpoints may have resulted more

  1. Stage of urinary bladder cancer at first presentation

    Directory of Open Access Journals (Sweden)

    Al-Bazzaz Pishtewan

    2009-01-01

    Full Text Available The stage of urinary bladder cancer is an important factor in determining prognosis of the disease. This prospective study was performed to determine the stage of bladder cancer at first presentation at the Rizgary Hospital in the Erbil governorate in Iraqi Kurdistan. We evaluated 72 patients with bladder cancer. The grades and stages of bladder cancer of these patients were determined through physical examination and investigations. We found that 47.2% of patients had superficial cancer, 19.4% had tumor with invasion into the lamina propria and 30.6% of patients had tumor with invasion to muscle wall. Regional or distant metastases were found in 2.8% of patients. Well differentiated tumor was seen in 44.4% of the patients, moderately differentiated tumor was found in 38.9% and poorly differentiated tumor was found in 16.7% of the patients. Our study suggests that bladder cancer is diagnosed at a relatively early stage in the Erbil governorate. However, the situation can be further improved by adopting proper screening programs and performing appropriate investigations.

  2. Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors

    Directory of Open Access Journals (Sweden)

    Michèle J. Hoffmann

    2015-12-01

    Full Text Available The INK4/ARF locus at chromosome 9p21 encoding p14ARF, p15INK4B and p16INK4A is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC. In addition to deletions and DNA hypermethylation, further epigenetic mechanisms might underlie its repression. One candidate factor is the long noncoding RNA ANRIL, which recruits Polycomb proteins (PcG to regulate expression of target genes in cis and trans. We observed ANRIL overexpression in many UC tissues and cell lines mainly resulting from upregulation of 3’-truncated isoforms. However, aberrant ANRIL expression was neither associated with repression of INK4/ARF genes nor with proliferation activity or senescence. We wondered whether truncated ANRIL isoforms exhibit altered properties resulting in loss of function in cis. We excluded delocalization and performed RNA immunoprecipitation demonstrating interaction between full length or truncated ANRIL and PcG protein CBX7, but not SUZ12 of PRC2. Our data indicate that ANRIL in UC cells may not interact with PRC2, which is central for initializing gene repression. Thus, tissue-specific binding activities between ANRIL and PcG proteins may determine the regulatory function of ANRIL. In conclusion, ANRIL does not play a major role in repression of the INK4/ARF locus in UC.

  3. Factors associated with tumor response and survival in radiosurgery for brain metastasis

    International Nuclear Information System (INIS)

    We reviewed our experience with radiosurgery for brain metastasis and focused on factors associated with tumor response and survival. Our study consists of 19 patients with 25 brain metastases who underwent linear accelerator radiosurgery. There was evidence of extra-central nervous system (CNS) tumors in 15 patients. The maximum diameter of the tumors ranged from 3 to 40 mm with a mean of 20 mm. Tumor doses at the isocenter varied from 16 to 25 Gy with a mean of 21 Gy. Eighteen lesions were treated by radiosurgery alone and 7 lesions received combined radiosurgery with fractionated radiotherapy. Of the 11 patients who experienced CNS failure either in or out of the radiosurgery field, 6 patients had salvage radiotherapy. Median survival was 7 months, and the 1-year actuarial survival rate was 40%. Death was due to extra-CNS tumor manifestations in 11 patients. In 3 patients, CNS failure was the cause of death. One died of local progression, and the other 2 died of newly developed metastases. Poor Karnofsky performance scores and the presence of extra-CNS tumors significantly affected 1-year survival in univariate analysis (p<0.05). Local tumor control was achieved in 80% of the lesions. The 1-year actuarial tumor control rate was 51%. Newly developed brain metastases were observed in 7 patients. The tumor diameter was mostly associated with tumor response in multiple regression analysis (p=0.0031). We concluded that radiosurgery is effective in controlling small brain metastases. Survival benefit is expected for those with good performance status and adequately controlled extra-CNS disease. (author)

  4. Survivin-specific T-cell reactivity correlates with tumor response and patient survival

    DEFF Research Database (Denmark)

    Becker, Jürgen C; Andersen, Mads H; Hofmeister-Müller, Valeska; Wobser, Marion; Frey, Lidia; Sandig, Christiane; Walter, Steffen; Singh-Jasuja, Harpreet; Kämpgen, Eckhart; Opitz, Andreas; Zapatka, Marc; Bröcker, Eva-B; thor Straten, Per; Schrama, David; Ugurel, Selma

    2012-01-01

    Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has...

  5. Early detection of antiangiogenic treatment responses in a mouse xenograft tumor model using quantitative perfusion MRI

    International Nuclear Information System (INIS)

    Angiogenesis plays a major role in tumor growth and metastasis, with tumor perfusion regarded as a marker for angiogenesis. To evaluate antiangiogenic treatment response in vivo, we investigated arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure tumor perfusion quantitatively. Chronic and 24-h acute treatment responses to bevacizumab were assessed by ASL and dynamic-contrast-enhanced (DCE) MRI in the A498 xenograft mouse model. After the MRI, tumor vasculature was assessed by CD34 staining. After 39 days of chronic treatment, tumor perfusion decreased to 44.8 ± 16.1 mL/100 g/min (P < 0.05), compared to 92.6 ± 42.9 mL/100 g/min in the control group. In the acute treatment study, tumor perfusion in the treated group decreased from 107.2 ± 32.7 to 73.7 ± 27.8 mL/100 g/min (P < 0.01; two-way analysis of variance), as well as compared with control group post dosing. A significant reduction in vessel density and vessel size was observed after the chronic treatment, while only vessel size was reduced 24 h after acute treatment. The tumor perfusion correlated with vessel size (r = 0.66; P < 0.005) after chronic, but not after acute treatment. The results from DCE-MRI also detected a significant change between treated and control groups in both chronic and acute treatment studies, but not between 0 and 24 h in the acute treatment group. These results indicate that tumor perfusion measured by MRI can detect early vascular responses to antiangiogenic treatment. With its noninvasive and quantitative nature, ASL MRI would be valuable for longitudinal assessment of tumor perfusion and in translation from animal models to human

  6. miRNAs modulate the drug response of tumor cells

    Institute of Scientific and Technical Information of China (English)

    WU XueMei; XIAO HuaSheng

    2009-01-01

    Chemotherapy is one of the major treatments of malignant carcinomas. However, its efficiency is af-fected by both intrinsic and acquired resistance to anticancer drugs. The cellular mechanisms of drug resistance include the overexpression of energy-dependent transporters that eject anticancer drugs from cells such as p-glycoprotein and multidrug resistance related protein (MRP), the mutation of drug targets, the activation of DNA repair pathways, the defects in cellular death pathways and so on. The genetic and epigenetic changes of these genes can lead to cancer drug resistance. Among these mechanisms, microRNAs (miRNAs) which are critical and essential for many important processes such as development, differentiation, and even carcinogenesis have been reported to regulate the chemo-sensitivity of tumor cells. In this paper we briefly review the relationship between miRNA and cancer drug resistance.

  7. miRNAs modulate the drug response of tumor cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Chemotherapy is one of the major treatments of malignant carcinomas. However,its efficiency is affected by both intrinsic and acquired resistance to anticancer drugs. The cellular mechanisms of drug resistance include the overexpression of energy-dependent transporters that eject anticancer drugs from cells such as p-glycoprotein and multidrug resistance related protein (MRP),the mutation of drug targets,the activation of DNA repair pathways,the defects in cellular death pathways and so on. The genetic and epigenetic changes of these genes can lead to cancer drug resistance. Among these mechanisms,microRNAs (miRNAs) which are critical and essential for many important processes such as development,differentiation,and even carcinogenesis have been reported to regulate the chemosen-sitivity of tumor cells. In this paper we briefly review the relationship between miRNA and cancer drug resistance.

  8. The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses

    OpenAIRE

    Maker, Ajay V; Prabhakar, Bellur; Pardiwala, Krunal

    2015-01-01

    Rose Bengal (RB) is a red synthetic dye that was initially used in the garment industry and has been used safely for decades as a corneal stain by ophthalmologists. Antineoplastic properties of RB have also been observed, though the mechanism of action remained to be elucidated. Recently, interest in RB as a therapeutic cancer treatment has increased due to significant anti-tumor responses with direct tumor injection in human clinical trials for metastatic melanoma. In these patients, there h...

  9. Magnetic resonance imaging in assessment of treatment response of gamma knife for brain tumors

    Institute of Scientific and Technical Information of China (English)

    GAO Xiao; ZHANG Xue-ning; ZHANG Yun-ting; YU Chun-shui; XU De-sheng

    2011-01-01

    Objective To review the applications of magnetic resonance imaging (MRI) techniques in assessing treatment response to gamma knife radiosurgery for brain tumors.Data sources Published articles about assessing treatment response to gamma knife radiosurgery for brain tumors were selected using PubMed. The search terms were "MRI", "gamma knife" and "brain tumors".Study selection Articles regarding the MRI techniques using for early assessment of treatment response of gamma knife were selected.Results MRI techniques, especially diffusion weighted imaging, perfusion weighted imaging, magnetic resonance spectroscopy, are useful for early assessment of treatment response of gamma knife by detecting the hemodynamic, metabolic, and cellular alterations. Moreover, they can also provide important information on prognosis.Conclusions Diffusion weighted imaging, perfusion weighted imaging and magnetic resonance spectroscopy can provide early assessment of treatment response of gamma knife for brain tumors, and also information of tumor progression or recurrence earlier than conventional MRI. But there are still many questions to be answered which should be based on the development and advancement of MRI and related disciplines.

  10. Effects of selenium on radiation responses of tumor cells and tissue

    International Nuclear Information System (INIS)

    Purpose: this review summarizes information about modulation of radiation effects in tumor cells and tissues by selenium. Results: in vitro, clonogenic survival to ionizing radiation was found to be reduced, depending on selenite concentration and duration of administration, by a factor of 1.5-4.4. In experimental animal tumors, a positive effect of selenium was observed with chemotherapy. The only available study in combination with irradiation did not show any benefit of selenium with clinically relevant radiotherapy protocols in R1H tumors. None of the investigations demonstrated a negative effect on the tumor response to therapy. Conclusion: the only study with fractionated irradiation was performed in a rat R1H tumor, which does not show accelerated repopulation. Therefore, interaction of selenium with such repopulation processes, potentially resulting in increased tumor tolerance, could not be detected. For local administration of normal tissues with selenium, potential tumor effects may be of less importance, but these may be relevant for systemic administration. Therefore, well-designed studies with relevant tumor models and endpoints, and with clinically relevant fractionation protocols are recommended. (orig.)

  11. Chemoimmunotherapy of murine bladder cancer.

    Science.gov (United States)

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  12. Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

    International Nuclear Information System (INIS)

    Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm3 size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1σ) for a mean dose response gradient γ in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs

  13. Bladder Cancer Stem-Like Cells: Their Origin and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Tomokazu Ohishi

    2015-12-01

    Full Text Available Bladder cancer (BC, the most common cancer arising from the human urinary tract, consists of two major clinicopathological phenotypes: muscle-invasive bladder cancer (MIBC and non-muscle-invasive bladder cancer (NMIBC. MIBC frequently metastasizes and is associated with an unfavorable prognosis. A certain proportion of patients with metastatic BC can achieve a remission with systemic chemotherapy; however, the disease relapses in most cases. Evidence suggests that MIBC comprises a small population of cancer stem cells (CSCs, which may be resistant to these treatments and may be able to form new tumors in the bladder or other organs. Therefore, the unambiguous identification of bladder CSCs and the development of targeted therapies are urgently needed. Nevertheless, it remains unclear where bladder CSCs originate and how they are generated. We review recent studies on bladder CSCs, specifically focusing on their proposed origin and the possible therapeutic options based on the CSC theory.

  14. Possible disease remission in patient with invasive bladder cancer with D-fraction regimen

    OpenAIRE

    Konno, Sensuke

    2009-01-01

    Srinivas Rajamahanty, Brandon Louie, Cormac O’Neill, Muhammad Choudhury, Sensuke KonnoDepartment of Urology, New York Medical College, Valhalla, New York, USAAbstract: Superficial bladder tumors are the most prevalent form of bladder cancers and transurethral resection is the primary surgical modality for those tumors. However, nearly 65% of patients will have tumor recurrence in five years while about 15% will have progression to muscle invasion. Thus, the primary therapeutic aim i...

  15. Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery

    International Nuclear Information System (INIS)

    Seventy patients with muscle-invading bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospective protocol from 1980 through 1985. Thirty-six patients are alive, all but three without evidence of cancer. The complete response rate is 77% in the 62 patients completing planned irradiation and 70% for all patients. Among the complete responders, 73% are currently maintained, and this group has a significantly higher four-year survival than those not having a complete response and those with recurrence of disease - 57% vs 11%. The observed high complete response rates in patients in all stages and the high survival rates suggest irradiation plus cisplatin therapy offers an important therapeutic gain over radiation therapy alone for invasive cancer of the bladder. These results encourage further evaluation of combining cisplatin-based, multidrug chemotherapy with irradiation in patients with locally very-advanced bladder tumors who are not suited for surgery

  16. Evaluation of In-111 DTPA-paclitaxel scintigraphy to predict response on murine tumors to paclitaxel

    International Nuclear Information System (INIS)

    Our goal was to determine whether scintigraphy with 111In-DTPA-paclitaxel could predict the response to chemotherapy with paclitaxel. Ovarian carcinoma (OCA 1), mammary carcinoma (MCA-4), fibrosarcoma (FSA) and squamous cell carcinoma (SCC VII) were inoculated into the thighs of female C3Hf/Kam mice. Mice bearing 8 mm tumors were treated with paclitaxel (40 mg/kg). The growth delay, which was defined as the time in days for tumors in the treated groups to grow from 8 to 12 mm in diameter minus the time in days for tumors in the untreated control group to reach the same size, was measured to determine the effect of paclitaxel on the tumors. Sequential scintigraphy in mice bearing 10 to 14 mm tumors was conducted at 5, 30, 60, 120, 240 min and 24 hrs postinjection of 111In-DTPA-paclitaxel (3.7 MBq) or 111In-DTPA as a control tracer. The tumor uptakes (% injection dose/pixel) were determined. The growth delay of OCA 1, MCA-4, FSA and SCC VII tumors was 13.6, 4.0, -0.02 and -0.28 days, respectively. In other words, OCA 1 and MCA-4 were paclitaxel-sensitive tumors, whereas FSA and SCC VII were paclitaxel-resistant tumors. The tumor uptakes at 24 hrs postinjection of In-111 DTPA paclitaxel of OCA 1, MCA-4, FSA and SCC VII were 1.0 x 10-3, 1.6 x 10-3, 2.2 x 10-3 and 9.0 x 10-3% injection dose/pixel, respectively. There was no correlation between the response to chemotherapy with paclitaxel and the tumor uptakes of 111In-DTPA-paclitaxel. Scintigraphy with 111In-DTPA-paclitaxel could not predict the response to paclitaxel chemotherapy. Although there was significant accumulation of the paclitaxel in the tumor cells, additional mechanisms must be operative for the agent to be effective against the neoplasm. 111In-DTPA-paclitaxel activity is apparently different from that of paclitaxel with Cremophor. (author)

  17. Automated detection of breast tumor in MRI and comparison of kinetic features for assessing tumor response to chemotherapy

    Science.gov (United States)

    Aghaei, Faranak; Tan, Maxine; Zheng, Bin

    2015-03-01

    Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) is used increasingly in diagnosis of breast cancer and assessment of treatment efficacy in current clinical practice. The purpose of this preliminary study is to develop and test a new quantitative kinetic image feature analysis method and biomarker to predict response of breast cancer patients to neoadjuvant chemotherapy using breast MR images acquired before the chemotherapy. For this purpose, we developed a computer-aided detection scheme to automatically segment breast areas and tumors depicting on the sequentially scanned breast MR images. From a contrast-enhancement map generated by subtraction of two image sets scanned pre- and post-injection of contrast agent, our scheme computed 38 morphological and kinetic image features from both tumor and background parenchymal regions. We applied a number of statistical data analysis methods to identify effective image features in predicting response of the patients to the chemotherapy. Based on the performance assessment of individual features and their correlations, we applied a fusion method to generate a final image biomarker. A breast MR image dataset involving 68 patients was used in this study. Among them, 25 had complete response and 43 had partially response to the chemotherapy based on the RECIST guideline. Using this image feature fusion based biomarker, the area under a receiver operating characteristic curve is AUC = 0.850±0.047. This study demonstrated that a biomarker developed from the fusion of kinetic image features computed from breast MR images acquired pre-chemotherapy has potentially higher discriminatory power in predicting response of the patients to the chemotherapy.

  18. Ultrasonic spectrum analysis for in vivo characterization of tumor microstructural changes in the evaluation of tumor response to chemotherapy using diagnostic ultrasound

    International Nuclear Information System (INIS)

    There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound. Experiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei. Treatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p < 0.05). The spectral slope increased by 48.5%, from −10.66 ± 2.96 to −5.49 ± 2.69; the midband-fit increased by 12.8%, from −57.10 ± 7.68 to −49.81 ± 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p < 0.001). Ultrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy

  19. Semiautomated volumetric response evaluation as an imaging biomarker in superior sulcus tumors

    International Nuclear Information System (INIS)

    Volumetric response to therapy has been suggested as a biomarker for patient-centered outcomes. The primary aim of this pilot study was to investigate whether the volumetric response to induction chemoradiotherapy was associated with pathological complete response (pCR) or survival in patients with superior sulcus tumors managed with trimodality therapy. The secondary aim was to evaluate a semiautomated method for serial volume assessment. In this retrospective study, treatment outcomes were obtained from a departmental database. The tumor was delineated on the computed tomography (CT) scan used for radiotherapy planning, which was typically performed during the first cycle of chemotherapy. These contours were transferred to the post-chemoradiotherapy diagnostic CT scan using deformable image registration (DIR) with/without manual editing. CT scans from 30 eligible patients were analyzed. Median follow-up was 51 months. Neither absolute nor relative reduction in tumor volume following chemoradiotherapy correlated with pCR or 2-year survival. The tumor volumes determined by DIR alone and DIR + manual editing correlated to a high degree (R2 = 0.99, P < 0.01). Volumetric response to induction chemoradiotherapy was not correlated with pCR or survival in patients with superior sulcus tumors managed with trimodality therapy. DIR-based contour propagation merits further evaluation as a tool for serial volumetric assessment. (orig.)

  20. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  1. Effects of increasing carbon nanofiber density in polyurethane composites for inhibiting bladder cancer cell functions.

    Science.gov (United States)

    Tsang, Melissa; Chun, Young Wook; Im, Yeon Min; Khang, Dongwoo; Webster, Thomas J

    2011-07-01

    Polyurethane (PU) is a versatile elastomer that is commonly used in biomedical applications. In turn, materials derived from nanotechnology, specifically carbon nanofibers (CNFs), have received increasing attention for their potential use in biomedical applications. Recent studies have shown that the dispersion of CNFs in PU significantly enhances composite nanoscale surface roughness, tensile properties, and thermal stability. Although there have been studies concerning normal primary cell functions on such nanocomposites, there have been few studies detailing cancer cell responses. Since many patients who require bladder transplants have suffered from bladder cancer, the ideal bladder prosthetic material should not only promote normal primary human urothelial cell (HUC) function, but also inhibit the return of bladder cancerous cell activity. This study examined the correlation between transitional (UMUC) and squamous (or SCaBER) urothelial carcinoma cells and HUC on PU:CNF nanocomposites of varying PU and CNF weight ratios (from pure PU to 4:1 [PU:CNF volume ratios], 2:1, 1:1, 1:2, and 1:4 composites to pure CNF). Composites were characterized for mechanical properties, wettability, surface roughness, and chemical composition by atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and goniometry. The adhesion and proliferation of UMUC and SCaBER cancer cells were assessed by MTS assays. Cellular responses were further quantified by measuring the amounts of nuclear mitotic protein 22 (NMP-22), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha. Results demonstrated that both UMUC and SCaBER cell proliferation rates decreased over time on substrates with increased CNF in PU. In addition, with the exception of VEGF from UMUC (which was the same across all materials), composites containing the most CNF activated cancer cells (UMUC and SCaBER) the least, as shown by

  2. Multidisciplinary Approach in the Treatment of Patients with Small Cell Bladder Carcinoma

    OpenAIRE

    Macedo, L. Traldi; Ribeiro, J.; Curigliano, G; Fumagalli, L.; Locatelli, M.; Campello Carvalheira, J. Barreto; Quintela, A.; Bertelli, S.; O. De Cobelli

    2011-01-01

    Abstract Small cell carcinoma of the urinary bladder (SCCUB) is considered to be a tumor with a neuroendocrine phenotype characterised by aggressive behaviour and poor prognosis. Small cell carcinoma of the urinary bladder comprises 0,35 to 1% of all bladder cancers and is frequently observed in combination with other histological subtypes of carcinoma. Clinical presentation is characterized by advanced stage at diagnosis and rapidly progressive disease. In daily clinical practice ...

  3. Small cell carcinoma of the urinary bladder: A case report and review of the literature

    OpenAIRE

    Ismaili Nabil; Ghanem Samia; Mellas Nawfel; Afqir Said; Taleb Meriem; Amrani Meryem; Gamra Lamia; Errihani Hassan

    2009-01-01

    Small cell carcinoma of the bladder (SCCB) is extremely rare. In this paper, we present a case of metastatic SCCB managed by chemotherapy and we would provide a brief review of the epidemiology, clinical features, diagnosis, pathologic features, staging, treatment, and prognosis of SCCB. A 52-year-old man was admitted with signs and symptoms suggestive of a bladder cancer. Computed tomography of the pelvis and abdomen showed a large tumor at the right bladder wall, measuring 10 cm in diameter...

  4. Small cell cancer of the bladder: The Leon-Berard cancer centre experience

    OpenAIRE

    Ismaili, Nabil; Elkarak, Fadi; Heudel, Pierre Etienne; Flechon, Aude; Droz, Jean Pierre

    2008-01-01

    Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre. Materials and Methods: We retrospectively analyzed various characteristics of small cell bladder carcinoma: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006. Results: The...

  5. Cellular origin of bladder neoplasia and tissue dynamics of its progression to invasive carcinoma

    OpenAIRE

    Shin, Kunyoo; Lim, Agnes; Odegaard, Justin I.; Honeycutt, Jared D.; Kawano, Sally; Hsieh, Michael H.; Beachy, Philip A.

    2014-01-01

    Understanding how malignancies arise within normal tissues requires identification of the cancer cell of origin and knowledge of the cellular and tissue dynamics of tumor progression. Here we examine bladder cancer in a chemical carcinogenesis model that mimics muscle-invasive human bladder cancer. With no prior bias regarding genetic pathways or cell types, we prospectively mark or ablate cells to show that muscle-invasive bladder carcinomas arise exclusively from Sonic hedgehog ( Shh )-expr...

  6. GATA3 in the urinary bladder: suppression of neoplastic transformation and down-regulation by androgens

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Miyamoto, Yurina; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    Recent evidence suggests the involvement of sex hormone receptors in bladder cancer initiation, while precise functions of androgens and estrogens in the carcinogenesis step remain poorly understood. We recently found down-regulation of GATA3, a zinc-finger transcription factor and a new urothelial marker, in bladder cancer, which also correlated with expression status of androgen receptor (AR) and estrogen receptors (ERs). We here assessed whether GATA3 acted as a suppressor of bladder tumor...

  7. Role of Gene Methylation in Antitumor Immune Response: Implication for Tumor Progression

    Energy Technology Data Exchange (ETDEWEB)

    Serrano, Alfonso; Castro-Vega, Isabel [Department of Immunology, Hospital Clinico Universitario, Campus Universitario Teatinos S/N, 29010 Malaga (Spain); Redondo, Maximino, E-mail: mredondo@hcs.es [Department of Biochemistry, CIBER ESP, Hospital Costa del Sol, Marbella, Málaga, Carretera de Cadiz km 187, 29603 (Spain)

    2011-03-29

    Cancer immunosurveillance theory has emphasized the role of escape mechanisms in tumor growth. In this respect, a very important factor is the molecular characterization of the mechanisms by which tumor cells evade immune recognition and destruction. Among the many escape mechanisms identified, alterations in classical and non-classical HLA (Human Leucocyte Antigens) class I and class II expression by tumor cells are of particular interest. In addition to the importance of HLA molecules, tumor-associated antigens and accessory/co-stimulatory molecules are also involved in immune recognition. The loss of HLA class I antigen expression and of co-stimulatory molecules can occur at genetic, transcriptional and post-transcriptional levels. Epigenetic defects are involved in at least some mechanisms that preclude mounting a successful host-antitumor response involving the HLA system, tumor-associated antigens, and accessory/co-stimulatory molecules. This review summarizes our current understanding of the role of methylation in the regulation of molecules involved in the tumor immune response.

  8. Tumor Cell Response to Synchrotron Microbeam Radiation Therapy Differs Markedly From Cells in Normal Tissues

    International Nuclear Information System (INIS)

    Purpose: High-dose synchrotron microbeam radiation therapy (MRT) can be effective at destroying tumors in animal models while causing very little damage to normal tissues. The aim of this study was to investigate the cellular processes behind this observation of potential clinical importance. Methods and Materials: MRT was performed using a lattice of 25 μm-wide, planar, polychromatic, kilovoltage X-ray microbeams, with 200-μm peak separation. Inoculated EMT-6.5 tumor and normal mouse skin tissues were harvested at defined intervals post-MRT. Immunohistochemical detection of γ-H2AX allowed precise localization of irradiated cells, which were also assessed for proliferation and apoptosis. Results: MRT significantly reduced tumor cell proliferation by 24 h post-irradiation (p = 0.002). An unexpected finding was that within 24 h of MRT, peak and valley irradiated zones were indistinguishable in tumors because of extensive cell migration between the zones. This was not seen in MRT-treated normal skin, which appeared to undergo a coordinated repair response. MRT elicited an increase in median survival times of EMT-6.5 and 67NR tumor-inoculated mice similar to that achieved with conventional radiotherapy, while causing markedly less normal tissue damage. Conclusions: This study provides evidence of a differential response at a cellular level between normal and tumor tissues after synchrotron MRT.

  9. Role of Gene Methylation in Antitumor Immune Response: Implication for Tumor Progression

    International Nuclear Information System (INIS)

    Cancer immunosurveillance theory has emphasized the role of escape mechanisms in tumor growth. In this respect, a very important factor is the molecular characterization of the mechanisms by which tumor cells evade immune recognition and destruction. Among the many escape mechanisms identified, alterations in classical and non-classical HLA (Human Leucocyte Antigens) class I and class II expression by tumor cells are of particular interest. In addition to the importance of HLA molecules, tumor-associated antigens and accessory/co-stimulatory molecules are also involved in immune recognition. The loss of HLA class I antigen expression and of co-stimulatory molecules can occur at genetic, transcriptional and post-transcriptional levels. Epigenetic defects are involved in at least some mechanisms that preclude mounting a successful host-antitumor response involving the HLA system, tumor-associated antigens, and accessory/co-stimulatory molecules. This review summarizes our current understanding of the role of methylation in the regulation of molecules involved in the tumor immune response

  10. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review.

    LENUS (Irish Health Repository)

    Shrotriya, Shiva

    2015-01-01

    A systematic literature review was done to determine the relationship between elevated CRP and prognosis in people with solid tumors. C-reactive protein (CRP) is a serum acute phase reactant and a well-established inflammatory marker. We also examined the role of CRP to predict treatment response and tumor recurrence.

  11. Preliminary results of a phase III trial of spontaneous animal tumors to heat and/or radiation: early normal tissue response and tumor volume influence on initial response

    International Nuclear Information System (INIS)

    A Phase III randomized trial was initiated to test the relative efficacies of heat alone, radiation alone and heat plus radiation using spontaneous malignancies in pet animals. Heat alone was inferior to the other two treatment arms as demonstrated by a significantly higher non-response rate and shorter response duration. The ratio of complete response rates (CR) for heat plus radiation to radiation alone or the thermal relative risk (TRR) was greater for tumors > 10 cm3 as compared to those 3 (TRR = 4.8 and 1.4, respectively). The overall TRR for complete responses was 2.3. The CR data for the combined therapy arm indicate at least an additive effect between heat and radiation for small tumors but most likely a synergistic effect in the larger tumor group. Based on the data currently available, no significant difference in response duration is observed between the two radiation arms, although a nonsignificant advantage to the combination therapy exists. Normal tissue effects were evaluated by incidence of full moist desquamation within the irradiated volume, late fibrosis and bone necrosis. Since the radiation skin dose depended upon the technique being used it was possible to estimate the dose to achieve moist desquamation in 50% of the animals (DD50) by a logistic regression model as being 3728 +/- 344 rad for radiation alone. Significant lowering of the DD50 was not observed for the addition of the heat to radiation. Low patient numbers where intact skin was heated prevented an accurate analysis of the effect, however

  12. Response of mouse transplantable tumor to Plumbago Rosea and plumbagin in combination with radiation

    International Nuclear Information System (INIS)

    The anticancer and radiosensibility effects of the alcoholic root extract of the medicinal plant Plumbago rosea and its active component plumbagin were studied on mouse Ehrilich ascites carcinoma, grown intraperitoneally in Swiss mice. Mice were injected i. p. with Plumbago extract (50 or 75 mg/kg) (10) or plumbagin (2.5 mg/kg) (4), (3 mg/kg) (3), (6 mg/kg) (1) starting from 24 h after tumor cell transplantation with or without one abdominal exposure to 7.5 Gy gamma radiation after the first drug dose. Tumor growth and mouse survival were studied for 120 days. Both treatments inhibited tumor growth and increased the life span. Combination with radiation further increased the life span and number of survivors indicating a response modifying effect on Ehrlich ascites tumor in vivo. The purified plumbagin was more toxic than the extract

  13. Response of mouse transplantable tumor to Plumbago Rosea and plumbagin in combination with radiation

    Energy Technology Data Exchange (ETDEWEB)

    Emerson Solomon, F.; Sharada, A.C.; Uma Devi, P. [Kasturba Medical College, Manipal (India)

    1994-12-31

    The anticancer and radiosensibility effects of the alcoholic root extract of the medicinal plant Plumbago rosea and its active component plumbagin were studied on mouse Ehrilich ascites carcinoma, grown intraperitoneally in Swiss mice. Mice were injected i. p. with Plumbago extract (50 or 75 mg/kg) (10) or plumbagin (2.5 mg/kg) (4), (3 mg/kg) (3), (6 mg/kg) (1) starting from 24 h after tumor cell transplantation with or without one abdominal exposure to 7.5 Gy gamma radiation after the first drug dose. Tumor growth and mouse survival were studied for 120 days. Both treatments inhibited tumor growth and increased the life span. Combination with radiation further increased the life span and number of survivors indicating a response modifying effect on Ehrlich ascites tumor in vivo. The purified plumbagin was more toxic than the extract.

  14. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder

    International Nuclear Information System (INIS)

    Purpose: To assess prognostic factors for bladder relapse and distant failure following definitive radiotherapy for invasive transitional cell carcinoma (TCC) of the bladder. Methods and Materials: Retrospective review of patients treated in the period 1977 to 1990 by definitive radiotherapy. The factors studied included age, sex, T stage, histological grade, tumor multiplicity, ureteric obstruction, total radiation dose, and use of neoadjuvant chemotherapy. The endpoints studied were bladder relapse and distant failure. Results: There were 342 patients with a mean follow-up time of 7.9 years. Bladder relapse was observed in 159 patients. The overall actuarial bladder relapse rate at 5 years was 55% (SE = 3%). Prognostic factors for a higher bladder relapse rate were: tumor multiplicity (p < 0.001), presence of ureteric obstruction (p = 0.001), and higher T stage (p 0.044). Distant failure occurred in 39 patients. The overall actuarial distant failure rate at 5 years was 28% (SE = 3%). Prognostic factors for a higher distant failure rate were: ureteric obstruction (p = 0.003) and higher T stage (p = 0.030). Conclusion: In our study, patients with invasive bladder TCC fell into distinct prognostic groups determined by the three independent factors, ureteric obstruction, tumor multiplicity, and T stage. These factors provided estimated risks of bladder relapse by 5 years which ranged from 34% to 91%. Knowledge of these prognostic factors can help in the selection of patients more suited for bladder preservation by definitive radiotherapy

  15. Long non-coding RNA-GAS5 acts as a tumor suppressor in bladder transitional cell carcinoma via regulation of chemokine (C-C motif) ligand 1 expression

    OpenAIRE

    CAO, QIFENG; Wang, Ning; QI, JUAN; GU, ZHENGQIN; SHEN, HAIBO

    2015-01-01

    Long non-coding RNAs (lncRNAs) have important roles in diverse biological processes, including transcriptional regulation, cell growth and tumorigenesis. The present study aimed to investigate whether lncRNA-growth arrest-specific (GAS)5 regulated bladder cancer progression via regulation of chemokine (C-C) ligand (CCL)1 expression. The viability of BLX bladder cancer cells was detected using a Cell Counting kit-8 assay, and cell apoptosis was assessed by annexin V-propidium iodide double-sta...

  16. A rare case of pure small cell carcinoma of urinary bladder

    Directory of Open Access Journals (Sweden)

    Sunita Singh

    2014-09-01

    Full Text Available Bladder cancer is the second most common urologic malignancy. Up to 95% of the urinary bladder tumors are of epithelial origin, from which 90% are transitional neoplasms. However, small cell carcinoma of the urinary bladder is rare tumor accounting for<0.7% of bladder cancer, of which the pure form is extremely rare. A 53‑year‑old female presented to urosurgery outpatient department complaining of hematuria and burning micturition since 3 months. Ultrsonography showed a large heteroechoic mass filling whole of the bladder. Histopathological examination of the transurethral debulked tumor mass revealed small cell carcinoma, which was confirmed on immunohistochemistry. We report this case due to its rarity and to add on to literature

  17. Acute phase response induced following tumor treatment by photodynamic therapy: relevance for the therapy outcome

    Science.gov (United States)

    Korbelik, Mladen; Merchant, Soroush; Stott, Brandon; Cecic, Ivana; Payne, Peter; Sun, Jinghai

    2006-02-01

    Acute phase response is an effector process orchestrated by the innate immune system for the optimal mobilization of the resources of the organism distant from the local insult site needed in the execution of a host-protecting reaction. Our research has shown that mice bearing tumors treated by photodynamic therapy (PDT) exhibit the three major hallmarks of acute phase response: release of acute phase reactants, neutrophilia, and pituitary/adrenal axis activation. Of particular interest in this study were acute phase proteins that have a pivotal role in the clearance of dead cells, since the occurrence of this process in PDT-treated tumors emerges as a critical event in the course of PDT-associated host response. It is shown that this type of acute phase reactants, including complement proteins (C3, C5, C9, mannose-binding lectin, and ficolin A) and related pentraxins (serum amyloid P component and PTX3), are upregulated following tumor PDT and accumulate in the targeted lesions. Based on the recently accumulated experimental evidence it is definitely established that the acute phase response is manifested in the hosts bearing PDT-treated tumors and it is becoming clear that this effector process is an important element of PDT-associated host response bearing in impact on the eventual outcome of this therapy.

  18. Large Cell Neuroendocrine Carcinoma of Urinary Bladder; Case Presentation

    Directory of Open Access Journals (Sweden)

    Ayşegül SARI

    2013-01-01

    Full Text Available Large cell neuroendocrine tumor of the urinary bladder is very rare. It is a type of neuroendocrine carcinoma that is morphologically different from small cell carcinoma.This manuscript describes a 67-year-old man who presented with hematuria. Ultrasonogrophic and computer tomography revealed a 5 cm mass in right posterolateral wall of the bladder that invaded perivesical tissue and he subsequently underwent transurethral resection. Microscopic examination showed a tumor with a sheet-like and trabecular growth pattern comprising necrotic areas which infiltrated the muscularis propria. Tumoral cells had coarse chromatin, prominent nucleoli, moderate amount of cytoplasm and immunohistochemically stained strongly positive with synaptophysin, chromogranin and CD56.There are only few case reports of large cell neuroendocrine tumor of the urinary bladder so the biological behavior and the treatment protocol of these tumors are still obscure. Appropriate management protocols and prognostic estimation could be achived by the increased number of cases being reported. Therefore in a case of a poorly differentiated tumor in bladder, although rare, it is important to consider large cell neuroendocrine carcinoma in differential diagnosis.

  19. In vivo optical imaging of tumor and microvascular response to ionizing radiation.

    Science.gov (United States)

    Maeda, Azusa; Leung, Michael K K; Conroy, Leigh; Chen, Yonghong; Bu, Jiachuan; Lindsay, Patricia E; Mintzberg, Shani; Virtanen, Carl; Tsao, Julissa; Winegarden, Neil A; Wang, Yanchun; Morikawa, Lily; Vitkin, I Alex; Jaffray, David A; Hill, Richard P; DaCosta, Ralph S

    2012-01-01

    Radiotherapy is a widely used cancer treatment. However, understanding how ionizing radiation affects tumor cells and their vasculature, particularly at cellular, subcellular, genetic, and protein levels, has been limited by an inability to visualize the response of these interdependent components within solid tumors over time and in vivo. Here we describe a new preclinical experimental platform combining intravital multimodal optical microscopy for cellular-level longitudinal imaging, a small animal x-ray microirradiator for reproducible spatially-localized millimeter-scale irradiations, and laser-capture microdissection of ex vivo tissues for transcriptomic profiling. Using this platform, we have developed new methods that exploit the power of optically-enabled microscopic imaging techniques to reveal the important role of the tumor microvasculature in radiation response of tumors. Furthermore, we demonstrate the potential of this preclinical platform to study quantitatively--with cellular and sub-cellular details--the spatio-temporal dynamics of the biological response of solid tumors to ionizing radiation in vivo. PMID:22927920

  20. CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

    Science.gov (United States)

    Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2015-11-01

    The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. PMID:25263481

  1. Cholesterol crystal embolization diagnosed on bladder transurethral resection.

    Science.gov (United States)

    Chatelain, Denis; Cordonnier, Carole; Brevet, Marie; Petit, Jacques; Sevestre, Henri

    2005-08-01

    Cholesterol crystal embolization (CCE) is a severe systemic disorder caused by vascular migration of cholesterol crystals originating from ulcerative atherosclerotic plaques located in large arteries. We report 2 cases of CCE diagnosed on bladder transurethral resection in 2 men aged 94 and 72 years. Both patients had atherosclerosis disease. One patient had been treated by heparin 1 month before for pulmonary embolism and the other had had a coronary angiography and bypass graft surgery 5 months before for silent myocardial infarction. One patient presented with hematuria and the other with acute renal failure. Cystoscopy showed multiple papillary tumors of the bladder wall. Bladder transurethral resections showed transitional cell carcinoma with cholesterol crystals occluding the lumen of small arterioles in the submucosa. Eight cases of CCE in the bladder wall have been reported in the literature in 3 women and 5 men aged 56 to 79 years. Cholesterol crystal embolization is often discovered in the bladder wall on necropsy specimens. Only 2 cases have been fortuitously discovered on bladder transurethral resection performed for transitional cell carcinoma. Cholesterol crystal embolization in the bladder wall is often a marker of severe disease although the evolution is quite favorable in our patients, still alive 1 and 2 years after diagnosis. PMID:16084459

  2. Concomitant boost radiotherapy for muscle invasive bladder cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the feasibility and efficacy of a concomitant partial bladder boost schedule in radiotherapy for invasive bladder cancer, coupling a limited boost volume with shortening of the overall treatment time. Methods and materials: Between 1994 and 1999, 50 patients with a T2-T4 N0M0 transitional cell carcinoma of the bladder received radiotherapy delivered in a short overall treatment time with a concomitant boost technique. With this technique a dose of 40 Gy in 2-Gy fractions was administered to the small pelvis with a concomitant boost limited to the bladder tumor area plus margin of 15 Gy in fractions of 0.75 Gy. The total tumor dose was 55 Gy in 20 fractions in 4 weeks. Toxicity was scored according to EORTC/RTOG toxicity criteria. Results: The feasibility of the treatment was good. Severe acute toxicity ≥G3 was observed in seven patients (14%). Severe late toxicity ≥G3 was observed in six patients (13%). Thirty-seven patients (74%) showed a complete and five (10 %) a partial remission after treatment. The actuarial 3-year freedom of local progression was 55%. Conclusion: In external radiotherapy for muscle invasive bladder cancer a concomitant boost technique coupling a partial bladder boost with shortening of the overall treatment time provides a high probability of local control with acceptable toxicity

  3. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;

    2006-01-01

    gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...

  4. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer.

    Directory of Open Access Journals (Sweden)

    Guadalupe Lorenzatti Hiles

    Full Text Available ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable

  5. Strategies of assessing and quantifying radiation treatment metabolic tumor response using F18 FDG Positron Emission Tomography (PET)

    International Nuclear Information System (INIS)

    The use of positron emission tomography (PET) using F-18 labeled fluorodeoxyglucose (FDG) for both oncology disease staging and radiation therapy target volume delineation has steadily increased over the last decade, and FDG-PET is today readily available in all major medical centers. The goal of anti tumor treatment, including chemotherapy and/or radiation therapy is to diminish a tumor cell population, ideally to the state of total eradication. Reducing the number of viable tumor cells can lead to a reduction in anatomical tumor size, and may also be correlated with decreased FDG uptake. Efforts to assess tumor response to therapy have attempted to describe and quantify changes in glucose utilization, also referred to as metabolic tumor response. In this review, an attempt is made to present and discuss methodologies to assess and quantify tumor metabolic response to radiation therapy or chemoradiation treatment courses.

  6. Nerve Disease and Bladder Control

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... KB) Alternate Language URL Nerve Disease and Bladder Control Page Content On this page: What bladder control ...

  7. Gall bladder distention in newborns.

    OpenAIRE

    Corbett, R P; Egner, J R

    1988-01-01

    Three cases of gall bladder distention in asphyxiated newborns are described. Clinical and ultrasound examination showed this to be a benign, transient phenomenon. A causal relation between tissue hypoxia and gall bladder distention is proposed.

  8. Hemorrhagic irradiation cystitis associated with bladder transitional cell carcinoma and effects of aluminium-ammonium sulfate irrigation for massive bladder hemorrage

    International Nuclear Information System (INIS)

    Although pelvic irradiation is carried out widely on patients with uterine cancer, a few reports have dealt with the occurence of secondary bladder tumors due to pelvic irradiation. Herein, we report a case of radiation induced bladder transitional cell carcinoma. A 72-year-old woman suffered hemorrhagic irradiation cystitis for 2 years in duration following 8000 rads radiotherapy received 4 years before. Primary uterine cervical cancer was well controlled and residual tumor or recurrence of tumor was excluded by clinical examination. Cystoscopic and cytologic examination was initiated in 1981 when first episode of hematuria occurred and was repeated there-after to check for neoplasm in the bladder until June 1983, when a bladder tumor was identified. Cystoscopy revealed a small papillary tumor in trigone, and hyperemic edema and bleeding in almost the whole bladder mucosa. The pathology of the tumor was transitional cell carcinoma. Hemorrhagic cystitis was treated successfully with bladder irrigation of 3 litres of 1% aluminium-ammonium sulfate solution after 3 courses of irrigation. (author)

  9. Unusual presentation of cutaneous metastasis from bladder urothelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chin-Pao Chang; I-Yen Lee; Hung-Jen Shih

    2013-01-01

    Cutaneous metastases from urothelial carcinoma of the bladder are a rare disease.In previous reports,the most common metastatic cutaneous lesions were non-tender nodules on the abdominal skin.We report a patient with bladder urothelial carcinoma with cutaneous metastases initially presenting as right leg and suprapubic lymphedema.Bladder tumor was the incidental finding by magnetic resonance venography.Urothelial carcinoma (clinical stage Ⅳ) was diagnosed,and chemotherapy was performed.Extensive painful erythematous plaques with an erysipelas-like appearance located on the suprapubic area,chest and abdomen were noted,and cutaneous metastases were confirmed by histopathology.Subsequently,extensive scrotal and prepuce ulcerative changes developed.This paper reports a rare case of extensive cutaneous metastasis of bladder urothelial carcinoma who presented an interesting clinical course.

  10. A phase I/II trial of transurethral surgery plus cisplatin and radiation therapy followed by either selective bladder preservation or radical cystectomy for patients with muscle-invading bladder cancer but without hydronephrosis

    International Nuclear Information System (INIS)

    Purpose/Objective: To explore the combination of transurethral surgery infusion 5-fluorouracil plus cisplatin and accelerated hyperfractionated radiation in the management of muscle-invading bladder cancer. Materials and Methods: 18 patients with Clinical Stage T2-T3b, Nx, M0 transitional cell carcinoma of the bladder without hydronephrosis were entered into a MGH protocol aimed at selective bladder conservation. Treatment began with as complete a transurethral resection as possible, followed by induction chemoradiation. This consisted of 5-FU 425 mg/m2 per day on days 1-4, cisplatin 20 mg/m2 per day on days 1-5 and 15-19. Twice-a-day radiation was delivered to the bladder and pelvis in a combination of 1.25 and 1.5 Gy fractions on days 1-5, 8-12, and 15-19 to a total dose of 42.5 Gy. Response was evaluated cystoscopically 3 weeks later. Patients with a complete response received consolidation therapy with cis-platinum 5-FU and a further 22.5 Gy radiation. Those who had not had a complete response were encouraged to undergo radical cystectomy. Adjuvant cisplatin, Methotrexate, and vinblastine was given to 13 patients for 3 cycles. Results: Of the 18 patients, 13 had visibly complete transurethral resections. Two patients did not complete the induction protocol as written due to acute toxicity. One was lost to follow-up at this stage. After induction treatment, 13 of the 18 patients had no tumor detectable on urine cytology or rebiopsy (a 72% complete response rate). Of the 5 patients who still had detectable tumor, 2 underwent radical cystectomy, one a partial cystectomy and 2 refused surgery and underwent consolidative chemoradiation instead. With a median follow-up of 20 months (range 9-30), 2 of the 16 patients with conserved bladders have experienced local relapse. In both of these, the relapse was superficial and managed by local measures without the need for radical surgery. No patient has required cystectomy for radiation morbidity. Two patients have

  11. Monitoring early tumor response to drug therapy with diffuse optical tomography

    Science.gov (United States)

    Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

    2012-01-01

    Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

  12. Plasticity in Tumor-Promoting Inflammation: Impairment of Macrophage Recruitment Evokes a Compensatory Neutrophil Response

    Directory of Open Access Journals (Sweden)

    Jessica C. Pahler

    2008-04-01

    Full Text Available Previous studies in the K14-HPV/E2 mouse model of cervical carcinogenesis demonstrated that infiltrating macrophages are the major source of matrix metalloproteinase 9 (MMP-9, a metalloprotease important for tumor angiogenesis and progression. We observed increased expression of the macrophage chemoattractant, CCL2, and its receptor, CCR2, concomitant with macrophage influx and MMP-9 expression. To study the role of CCL2-CCR2 signaling in cervical tumorigenesis, we generated CCR2-deficient K14-HPV/E2 mice. Cervixes of CCR2-null mice contained significantly fewer macrophages. Surprisingly, there was only a modest delay in time to progression from dysplasia to carcinoma in the CCR2-deficient mice, and no difference in end-stage tumor incidence or burden. Moreover, there was an unexpected persistence of MMP-9 activity, associated with increased abundance of MMP-9+ neutrophils in tumors from CCR2-null mice. In vitro bioassays revealed that macrophages produce soluble factor(s that can suppress neutrophil dynamics, as evidenced by reduced chemotaxis in response to CXCL8, and impaired invasion into three-dimensional tumor masses grown in vitro. Our data suggest a mechanism whereby CCL2 attracts proangiogenic CCR2+ macrophages with the ancillary capability to limit infiltration by neutrophils. If such tumor-promoting macrophages are suppressed, MMP-9+ neutrophils are then recruited, providing alternative paracrine support for tumor angiogenesis and progression.

  13. Visualization of tumor vascular reactivity in response to respiratory challenges by optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Kim, Hoon Sup; Lee, Songhyun; Lee, Kiri; Eom, Tae Joong; Kim, Jae G.

    2016-02-01

    We previously reported the potential of using vascular reactivity during respiratory challenges as a marker to predict the response of breast tumor to chemotherapy in a rat model by using a continuous wave near-infrared spectroscopy. However, it cannot visualize how the vascular reactivity from tumor vessel can predict the tumor response to its treatment. In this study, we utilized a spectral domain optical coherence tomography (SD-OCT) system to visualize vascular reactivity of both tumor and normal vasculature during respiratory challenges in a mouse model. We adapted intensity based Doppler variance algorithm to draw angiogram from the ear of mouse (8-week-old Balb/c nu/nu). Animals were anesthetized using 1.5% isoflurane, and the body temperature was maintained by a heating pad. Inhalational gas was switched from air (10min) to 100% oxygen (10min), and a pulse oximeter was used to monitor arterial oxygen saturation and heart rate. OCT angiograms were acquired 5 min after the onset of each gas. The vasoconstriction effect of hyperoxic gas on vasculature was shown by subtracting an en-face image acquired during 100% oxygen from the image acquired during air inhalation. The quantitative change in the vessel diameter was measured from the en-face OCT images of the individual blood vessels. The percentage of blood vessel diameter reduction varied from 1% to 12% depending on arterial, capillary, or venous blood vessel. The vascular reactivity change during breast tumor progression and post chemotherapy will be monitored by OCT angiography.

  14. Misonidazole in patients receiving radical radiotherapy: pharmacokinetic effects of phenytoin tumor response and neurotoxicity

    International Nuclear Information System (INIS)

    In 1978, a pilot study began of 29 patients with advanced tumors of the head and neck. The study showed an initial peripheral neuropathy rate of 55%, despite a dose limitation of 12 g/m2 of misonidazole. Tumor response at 9 months was most encouraging. We are now able to examine tumor response and persistence of neuropathy in these patients 2 1/2 years after radical radiotherapy. The results are comparable with those obtained with hyperbaric oxygen in a clinical trial at this center during the 1970's. Neuropathy was a serious side effect but the drug phenytoin has been shown to shorten the half-life of misonidazole. We have examined the effect of phenytoin on the pharmacokinetics of misonidazole in 13 patients who received radical radiotherapy for advanced head and neck tumors or oesophageal tumors. Misonidazole was given in multiple doses, i.e. daily or weekly as it would be used in conventional therapy. Phenytoin was given either daily throughout treatment, or it was withdrawn during treatment. There were dramatic changes in the half-life of misonidazole, but the concentration at the time of irradiation was little affected. The significant changes in the half-life of misonidazole and the increased concentration of the metabolite desmethylmisonidazole are discussed

  15. Enzyme responsive mesoporous silica nanoparticles for targeted tumor therapy in vitro and in vivo

    Science.gov (United States)

    Liu, Junjie; Zhang, Beilu; Luo, Zhong; Ding, Xingwei; Li, Jinghua; Dai, Liangliang; Zhou, Jun; Zhao, Xiaojing; Ye, Jingya; Cai, Kaiyong

    2015-02-01

    This study reports a biocompatible controlled drug release system based on mesoporous silica nanoparticles (MSNs) for tumor microenvironment responsive drug delivery. It was fabricated by grafting phenylboronic acid conjugated human serum albumin (PBA-HSA) onto the surfaces of MSNs as a sealing agent, via an intermediate linker of a functional polypeptide, which was composed of two functional units: the polycation cell penetrating peptide (CPP) polyarginine, and matrix metalloproteinase 2 (MMP-2) substrate peptide. A series of characterizations confirmed that the system had been successfully constructed. In vitro tests proved that the anticancer drug loading system could efficiently induce cell apoptosis in vitro. More importantly, the in vivo tumor experiments confirmed that the anticancer loading system could efficiently inhibit tumor growth with minimal side effects.This study reports a biocompatible controlled drug release system based on mesoporous silica nanoparticles (MSNs) for tumor microenvironment responsive drug delivery. It was fabricated by grafting phenylboronic acid conjugated human serum albumin (PBA-HSA) onto the surfaces of MSNs as a sealing agent, via an intermediate linker of a functional polypeptide, which was composed of two functional units: the polycation cell penetrating peptide (CPP) polyarginine, and matrix metalloproteinase 2 (MMP-2) substrate peptide. A series of characterizations confirmed that the system had been successfully constructed. In vitro tests proved that the anticancer drug loading system could efficiently induce cell apoptosis in vitro. More importantly, the in vivo tumor experiments confirmed that the anticancer loading system could efficiently inhibit tumor growth with minimal side effects. Electronic supplementary information (ESI) available: FTIR spectra, TGA curves, BET and BJH parameters, zeta potentials of nanoparticles; cleavage assay of the peptide detected by HPLC and MS; dose-dependent cytotoxicity of MSNs

  16. Enhancement of tumor radiation response by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid

    International Nuclear Information System (INIS)

    Purpose: 5,6-dimethylxanthenone-4-acetic acid (DMXAA) selectively damages tumor vasculature and is currently in clinical trial as an antitumor agent. Its ability to induce synthesis of tumor necrosis factor (TNF), and its apparent selectivity for poorly-perfused regions in tumors, suggests it possible use in combination with radiotherapy. This investigation examines activity of DMXAA as a radiation modifier using two murine tumors. Methods and Materials: Tumor growth delay was evaluated using i.m. RIF-1 and MDAH-MCa-4 tumors irradiated in unanaesthetised, restrained mice (cobalt-60) using single dose or multiple fractions (8 x 2.5 Gy over 4 days) with DMXAA administered i.p. at various times in relation to irradiation. Results: Administration of DMXAA (80 μmol/kg, i.p.) immediately after radiation resulted in a large increase in tumor growth delay, giving a radiation dose modifying factor of 2.3 for RIF-1 and 3.9 for MDAH-MCa-4. The combination was less active when radiation was given 1-4 h after DMXAA, but was highly active 12-48 h after DMXAA. At the latter times, clamping the tumor blood supply caused a large increase in radioresistance. These studies suggest that cells surviving DMXAA are hypoxic for only a short period. DMXAA increased overall growth delay when administered daily during fractionated irradiation, giving an approximately additive response. Conclusions: The marked synergy between DMXAA and single dose ionising radiation may reflect the complementarity of these agents at the microregional level, with DMXAA preferentially killing hypoxic cells in poorly perfused regions. Despite additional hypoxia shortly after DMXAA treatment, surviving cells appear to reoxygenate quickly which makes it feasible to use DMXAA before and during fractionated radiotherapy. The combination of fractionated radiation and DMXAA appears to be less effective than for single dose radiation (possibly because of the smaller contribution of hypoxia under these conditions), but

  17. Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer

    OpenAIRE

    García-Martínez, Elena; Gil, Ginés Luengo; Benito, Asunción Chaves; González-Billalabeitia, Enrique; Conesa, María Angeles Vicente; García, Teresa García; García-Garre, Elisa; Vicente, Vicente; de la Peña, Francisco Ayala

    2014-01-01

    Introduction Tumor microenvironment immunity is associated with breast cancer outcome. A high lymphocytic infiltration has been associated with response to neoadjuvant chemotherapy, but the contribution to response and prognosis of immune cell subpopulations profiles in both pre-treated and post-treatment residual tumor is still unclear. Methods We analyzed pre- and post-treatment tumor-infiltrating immune cells (CD3, CD4, CD8, CD20, CD68, Foxp3) by immunohistochemistry in a series of 121 bre...

  18. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  19. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    International Nuclear Information System (INIS)

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

  20. Targeting the tumor-draining area : local immunotherapy and its effect on the systemic T cell response

    NARCIS (Netherlands)

    Herbert-Fransen, Marieke Fernande

    2012-01-01

    This dissertation deals with the role of local immune stimulation in the lymph node and tumor microenvironment and its effect on systemic CD8+ T cell responses, in particular the anti-tumor CD8+ T cell responses. In chapter 2 the use of a slow-release system is described to deliver the immune-acti

  1. SU-E-QI-20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

    Energy Technology Data Exchange (ETDEWEB)

    Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States)

    2014-06-15

    Purpose: To review the literature in using quantitative PET and CT image features for the evaluation of tumor response. Methods: We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease-specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features. Results: Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Conclusions: Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi-modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

  2. Steering tumor progression through the transcriptional response to growth factors and stroma.

    Science.gov (United States)

    Feldman, Morris E; Yarden, Yosef

    2014-08-01

    Tumor progression can be understood as a collaborative effort of mutations and growth factors, which propels cell proliferation and matrix invasion, and also enables evasion of drug-induced apoptosis. Concentrating on EGFR, we discuss downstream signaling and the initiation of transcriptional events in response to growth factors. Specifically, we portray a wave-like program, which initiates by rapid disappearance of two-dozen microRNAs, followed by an abrupt rise of immediate early genes (IEGs), relatively short transcripts encoding transcriptional regulators. Concurrent with the fall of IEGs, some 30-60 min after stimulation, a larger group, the delayed early genes, is up-regulated and its own fall overlaps the rise of the final wave of late response genes. This late wave persists and determines long-term phenotype acquisition, such as invasiveness. Key regulatory steps in the orderly response to growth factors provide a trove of potential oncogenes and tumor suppressors. PMID:24873881

  3. Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures.

    Science.gov (United States)

    Yu, Kun-Hsing; Levine, Douglas A; Zhang, Hui; Chan, Daniel W; Zhang, Zhen; Snyder, Michael

    2016-08-01

    Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers. PMID:27312948

  4. Supraadditive apoptotic response of R3327-G rat prostate tumors to androgen ablation and radiation

    International Nuclear Information System (INIS)

    Purpose: Androgen ablation is often combined with radiation in the treatment of patients with prostate cancer, yet, the optimal sequencing and the mechanisms governing the interaction are not understood. The objectives were to determine if cell killing via apoptosis is enhanced when the combined treatment is administered and to define the relationship of changes in this form of cell killing to tumor volume growth delay. Materials and Methods: Dunning R3327-G rat prostate tumors, grown in the flanks of Copenhagen rats, were used at a volume of approximately 1 cc. Androgen ablation was initiated by castration, and androgen restoration was achieved with 0.5 cm silastic tube implants containing testosterone. 60Co was used for irradiation. The terminal deoxynucleotidyl transferase (TUNEL) histochemical assay was used to quantify apoptosis. Results: Tumors from intact and castrate unirradiated control rats had average apoptotic indices (percent of apoptotic cells) of 0.4 and 1.0%, respectively. The apoptotic index varied only slightly over time (3 h to 28 days) after castration (range 0.75-1.43%). Irradiation of intact rats to 7 Gy resulted in a peak apoptotic response at 6 h of 2.3%. A supra additive apoptotic response was seen when castration was initiated 3 days prior to 7 Gy radiation, with peak levels of about 10.1%. When the radiation was administered at increasing times beyond 3 days after castration, the apoptotic response gradually diminished and was back to levels seen in intact rats by 28 days after castration. Tumor volume growth delay studies were consistent with, but not conclusive proof of, a supra additive effect when the combination was used. Discussion: A supra additive apoptotic response was seen when androgen ablation and radiation were used to treat androgen sensitive R3327-G rat prostate tumors. This supra additive effect was dependent on the timing of the two treatments. Further studies are required to more fully define the optimal timing and

  5. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    International Nuclear Information System (INIS)

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy

  6. Response of human tumor cell lines in vitro to fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Matthews, J.H.; Meeker, B.E.; Chapman, J.D.

    1989-01-01

    The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SF2 of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37 degrees C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22 degrees C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment.

  7. Response of human tumor cell lines in vitro to fractionated irradiation.

    Science.gov (United States)

    Matthews, J H; Meeker, B E; Chapman, J D

    1989-01-01

    The surviving fraction of human tumor cell lines after 2 Gy (SF2) varies between 0.1 and 0.8. It has been postulated that differences in inherent radiosensitivity of tumor cells are a major determinant of radiation response in vivo. Assays of inherent radiosensitivity based on acute survival are being developed as predictors of tumor response which often assume that the same inherent radiosensitivity persists throughout a fractionated treatment. We have investigated the response of 2 human tumor cell lines (A549 and MCF7) with different inherent radiosensitivities to in vitro fractionated irradiation. A549 cells had an SF2 of 0.62 and a mean inactivation dose (D) of 3.07 Gy whereas MCF7 cells had an SF2 of 0.30 and a D of 1.52 Gy. Split dose repair capacity (at equal survival levels) was less for A549 than for MCF7 cells and recovery kinetics for both cell lines were substantially longer than those of rodent cell lines. Survival after 5 fractions of 2 Gy given 12 hr apart at 37 degrees C was near to that predicted from the acute survival curve, assuming complete repair and no proliferation. Acute survival of A549 cells which survived 5 fractions of 2 Gy given 12 hr apart was similar to the acute survival of unirradiated cells. When A549 cells were incubated at 22 degrees C between 5 fractions of 2 Gy given 12 hr apart, proliferation and split dose repair were substantially inhibited. These studies support the proposals to use in vitro inherent radiosensitivity assays for the prediction of in vivo response of tumors to fractionated treatment. PMID:2912934

  8. Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin, E-mail: Bin.Zheng-1@ou.edu [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Hollingsworth, Alan B. [Mercy Women’s Center, Mercy Health Center, Oklahoma City, Oklahoma 73120 (United States); Qian, Wei [Department of Electrical and Computer Engineering, University of Texas, El Paso, Texas 79968 (United States)

    2015-11-15

    Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

  9. Probiotics, dendritic cells and bladder cancer.

    Science.gov (United States)

    Feyisetan, Oladapo; Tracey, Christopher; Hellawell, Giles O

    2012-06-01

    What's known on the subject? and What does the study add? The suppressor effect of probiotics on superficial bladder cancer is an observed phenomenon but the specific mechanism is poorly understood. The evidence strongly suggests natural killer (NK) cells are the anti-tumour effector cells involved and NK cell activity correlates with the observed anti-tumour effect in mice. It is also known that dendritic cells (DC) cells are responsible for the recruitment and mobilization of NK cells so therefore it may be inferred that DC cells are most likely to be the interphase point at which probiotics act. In support of this, purification of NK cells was associated with a decrease in NK cells activity. The current use of intravesical bacille Calmette-Guérin in the management of superficial bladder cancer is based on the effect of a localised immune response. In the same way, understanding the mechanism of action of probiotics and the role of DC may potentially offer another avenue via which the immune system may be manipulated to resist bladder cancer. Probiotic foods have been available in the UK since 1996 with the arrival of the fermented milk drink (Yakult) from Japan. The presence of live bacterial ingredients (usually lactobacilli species) may confer health benefits when present in sufficient numbers. The role of probiotics in colo-rectal cancer may be related in part to the suppression of harmful colonic bacteria but other immune mechanisms are involved. Anti-cancer effects outside the colon were suggested by a Japanese report of altered rates of bladder tumour recurrence after ingestion of a particular probiotic. Dendritic cells play a central role to the general regulation of the immune response that may be modified by probiotics. The addition of probiotics to the diet may confer benefit by altering rates of bladder tumour recurrence and also alter the response to immune mechanisms involved with the application of intravesical treatments (bacille Calmette

  10. Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States); Jia Xiaoyu, E-mail: jiax@mskcc.org; Gonen, Mithat, E-mail: gonenm@mskcc.org [Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics (United States); Brown, Karen T., E-mail: brown6@mskcc.org; Sofocleous, Constantinos T., E-mail: sofoclec@mskcc.org; Getrajdman, George I., E-mail: getrajdg@mskcc.org; Brody, Lynn A., E-mail: brodyl@mskcc.org; Thornton, Raymond H., E-mail: throntor@mskcc.org; Maybody, Majid, E-mail: maybodym@mskcc.org; Covey, Ann M., E-mail: covey@mskcc.org; Siegelbaum, Robert H., E-mail: siegelbr@mskcc.org; Alago, William, E-mail: alagow@mskcc.org; Solomon, Stephen B., E-mail: solomons@mskcc.org [Memorial Sloan-Kettering Cancer Center, Interventional Radiology Service, Department of Radiology (United States)

    2013-08-01

    PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrast retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.

  11. Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

    International Nuclear Information System (INIS)

    PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 ± 7.7 weeks after embolization). Tumor contrast retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria

  12. Optical properties of tumor tissues grown on the chorioallantoic membrane of chicken eggs: tumor model to assay of tumor response to photodynamic therapy

    Science.gov (United States)

    Honda, Norihiro; Kariyama, Yoichiro; Hazama, Hisanao; Ishii, Takuya; Kitajima, Yuya; Inoue, Katsushi; Ishizuka, Masahiro; Tanaka, Tohru; Awazu, Kunio

    2015-12-01

    Herein, the optical adequacy of a tumor model prepared with tumor cells grown on the chorioallantoic membrane (CAM) of a chicken egg is evaluated as an alternative to the mouse tumor model to assess the optimal irradiation conditions in photodynamic therapy (PDT). The optical properties of CAM and mouse tumor tissues were measured with a double integrating sphere and the inverse Monte Carlo technique in the 350- to 1000-nm wavelength range. The hemoglobin and water absorption bands observed in the CAM tumor tissue (10 eggs and 10 tumors) are equal to that of the mouse tumor tissue (8 animals and 8 tumors). The optical intersubject variability of the CAM tumor tissues meets or exceeds that of the mouse tumor tissues, and the reduced scattering coefficient spectra of CAM tumor tissues can be equated with those of mouse tumor tissues. These results confirm that the CAM tumor model is a viable alternative to the mouse tumor model, especially for deriving optimal irradiation conditions in PDT.

  13. Bilateral Ovarian Dermoid Cyst with Bladder Involvement and Hematuria: A Case Report and Literature Review

    OpenAIRE

    Mohammad Mehdi Hosseini; Shahrokh Jahanbini; Sara Pakbaz; Shahryar Zeighami

    2014-01-01

    Bilateral ovarian dermoid tumor with invasion to surrounding organ is a rare entity. We report the case of a 63-year-old woman with prolonged dysuria and hematuria who had bilateral ovarian dermoid cysts with urinary bladder involvement.

  14. Urinary Bladder Adenocarcinoma Metastatic to the Abdominal Wall: Report of a Case with Cytohistologic Correlation

    Directory of Open Access Journals (Sweden)

    Vikas Nath

    2016-01-01

    Full Text Available We report a case of adenocarcinoma metastatic to the abdominal wall in a 71-year-old man with a history of primary bladder adenocarcinoma. CT-guided core biopsy was performed; imprints and histologic sections showed malignant glands lined by tumor cells with hyperchromatic nuclei and prominent nucleoli, infiltrating through skeletal muscle. Immunohistochemistry revealed positivity for CK7, membranous/cytoplasmic β-catenin, caudal-type homeobox transcription factor 2 (CDX2, and α-methylacyl coenzyme A racemase and negativity for CK20, p63, prostate-specific antigen (PSA, and prostate-specific acid phosphatase (PSAP.