Effects of curcumin in an orthotopic murine bladder tumor model

Cigarette smoking (CS) is the main risk factor for bladder cancer development. There are more than 100 carcinogens present in cigarette smoke. Among the potential mediators of CS-induced alterations is nuclear factor-kappa (NF-κB), which is responsible for the transcription of genes related to cell transformation, tumor promotion, angiogenesis, invasion and metastasis. Curcumin is a polyphenol compound derived from Curcuma longa that suppress cellular transformation, proliferation, invasion, angiogenesis, and metastasis by down regulating NF-κB and its regulated genes. The aim of our study was to assess the effects of curcumin in bladder urothelial carcinoma. We studied the effects of curcumin in vitro and in vivo using the orthotropic syngeneic bladder tumor animal model MB49. Curcumin promotes apoptosis of bladder tumor cells in vitro. In vivo tumors of animals treated with curcumin were significantly smaller as compared to controls. Using immunohistochemistry, we demonstrated a decrease in the expression of Cox-2 by 8% and Cyclin D1 by 13% in the animals treated with curcumin; both genes regulated by NF-κB and related to cell proliferation. In this study, we showed that curcumin acts in bladder urothelial cancer, possibly dowregulating NF-κB-related genes, and could be an option in the treatment of urothelial neoplasms. The results of our study suggest that further research is warranted to confirm our findings

Prognostic relevance of the histological subtype of renal cell carcinoma

OBJECTIVE: According to several studies, when the histological subtype of renal cell carcinoma is established it is possible to attribute a different life expectancy to each patient. We analyzed the prognostic significance of the histological subtype in renal cell carcinoma. MATERIALS AND METHODS: The authors retrospectively analyzed the follow-up of 230 patients after radical or conservative renal surgery. The histological characteristics of the different subtypes of tumor were obtained and the disease-free and cancer-specific survival curves for the clear cell, cromophobic, papillary, collecting duct (Bellini) subtypes and those with sarcomatoid differentiation were individualized. RESULTS: The disease-free and cancer-specific survival rates for clear cell tumors were 76.6% and 68.0% respectively, 71.2% and 82.1% respectively for the cromophobic type, 71.1% and 79.8% respectively for the papillary type, 26.9% and 39.3% respectively for the sarcomatoid type, and 0.0% and 0.0% respectively for the collecting ducts (p < 0.001). CONCLUSION: The histological subtypes of renal tumors can stratify patients into different prognostic groups only when the sarcomatoid differentiation is present

Correlation between specific IgM levels and percentage IgG-class antibody avidity to Toxoplasma gondii

Toxoplasmosis is an usually asymptomatic worldwide disseminated infection. In its congenital presentation it may lead to abortion or fetal malformations. Antenatal evaluation is considered of paramount importance to identify seronegative women and allow for prophylaxis. Recent improvements in sensitivity of IgM tests has made IgM detection an extremely protracted acute phase marker, and IgG avidity evaluation test became necessary. Observation has shown that a correlation can be established between IgM levels and avidity percentages, suggesting that frequently the avidity test may not be necessary. In this study we analyzed Toxoplasma gondii IgM levels of 202 samples and their IgG avidity percentages, in order to define specific levels whose IgM quantification could by itself define serodiagnosis and therefore make the avidity evaluation unnecessary. We showed that for IgM levels bellow 2.0 and above 6.0 serodiagnosis of toxoplasmosis could be established without need of IgG avidity test. IgM levels between these two parameters are associated with varying avidity indexes highlighting the importance of its evaluation as a means to confirm toxoplasmosis. Following this demonstration it was possible to avoid the avidity test for 75% of the cases, to reduce the turnaround time and to reduce costs.A Toxoplasmose é uma infecção universal e usualmente assintomática. A forma congênita, entretanto, pode resultar em aborto ou mal formações. Testes sorológicos estão indicados em situações onde há suspeita clínica, e na triagem pré-natal, quando são extremamente importantes para rastrear a infecção e orientar a gestante. O aumento da sensibilidade das técnicas para detecção de IgM, tornou necessário o desenvolvimento de recursos, como a avidez de IgG, visando obter novo marcador de infecção aguda. Embora exista correlação entre níveis de IgM e grau de avidez de IgG, a maioria dos testes de avidez associa-se a níveis baixos de IgM, sugerindo que o teste de avidez não fosse necessário. Portanto, correlacionamos níveis de IgM de 202 amostras com seu respectivo nível de avidez de IgG, dirigidos contra o Toxoplasma, objetivando estabelecer valores claros para a sua indicação. Pôde-se observar que, para IgM ; 6,0, a definição sorológica pode ser feita independentemente da avidez. Níveis de IgM dentro desse intervalo associam-se a índices variados de avidez e, portanto, ressaltam a importância deste teste para definição sorológica do quadro. Com essa abordagem, foi possível diminuir a indicação do teste de avidez em 75%, reduzir o tempo para liberação dos resultados e o custo unitário do teste para IgM

Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer

The use of immunohistochemistry for diagnosis of prostate cancer

PURPOSE: Atypical glands (ASAP) are diagnosed in 5.0% of prostate biopsies, and cancer identification in a rebiopsy is higher than 40.0%. The use of antibodies to mark basal cells is currently a common practice, in order to avoid rebiopsies. There has been no reported study that has reviewed characteristics of radical prostatectomies (RPs) when immunohistochemistry (IHC) was necessary for definitive diagnosis. MATERIALS AND METHODS: Out of 4127 biopsies examined from 2004 to 2008, 144 (3.5%) were diagnosed with ASAP. IHC was performed using antibody anti-34ßE12 and p63. The results of surgical specimens of 27 patients treated by RP after the diagnosis of prostate cancer (PC) was made using IHC (Group 1) were compared with 1040 patients where IHC was not necessary (Group 2). RESULTS: IHC helped to diagnose PC in 103 patients (71.5%). Twenty-seven (26.2%) underwent RP. In Group 1, two (7.4%) adenocarcinomas were insignificant versus 29 (2.9%) for Group 2. Patients from Group 1 were younger (p = 0.039), had lower Gleason scores (GS) (p < 0.001), lower percentage of Gleason pattern 4 (p < 0.001), and smaller tumors (p < 0.001). CONCLUSION: The use of IHC did not lead to diagnosis of insignificant tumors as illustrated by absence of differences in pathological stage or positive surgical margins in men submitted to RP. Therefore, our results suggest that this modality should be routinely used for a borderline biopsy and ASAP cases

Curcumin, but not Prima-1, decreased tumor cell proliferation in the syngeneic murine orthotopic bladder tumor model

OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer

Urinary glycosaminoglycans excretion and the effect of dimethyl sulfoxide in an experimental model of non-bacterial cystitis

PURPOSE: We reproduced a non-bacterial experimental model to assess bladder inflammation and urinary glycosaminoglycans (GAG) excretion and examined the effect of dimethyl sulfoxide (DMSO). MATERIALS AND METHODS: Female rats were instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24 h urine and bladder samples were obtained. Urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycans (S-GAG) were determined. Also to evaluate the effect of DMSO animals were instilled with either 50% DMSO or saline 6 hours after PS instillation. To evaluate the effect of DMSO in healthy bladders, rats were instilled with 50% DMSO and controls with saline. RESULTS: In the PS groups, bladder inflammation was observed, with polymorphonuclear cells during the first days and lymphomononuclear in the last days. HA and S-GAG had 2 peaks of urinary excretion, at the 1st and 7th day after PS injection. DMSO significantly reduced bladder inflammation. In contrast, in healthy bladders, DMSO produced mild inflammation and an increase in urinary HA levels after 1 and 7 days and an increase of S-GAG level in 7 days. Animals instilled with PS and treated with DMSO had significantly reduced levels of urinary HA only at the 1st day. Urinary S-GAG/Cr levels were similar in all groups. CONCLUSIONS: Increased urinary levels of GAG were associated with bladder inflammation in a PS-induced cystitis model. DMSO significantly reduced the inflammatory process after urothelial injury. Conversely, this drug provoked mild inflammation in normal mucosa. DMSO treatment was shown to influence urinary HA excretion

Early experience with targeted therapy and dendritic cell vaccine in metastatic renal cell carcinoma after nephrectomy

PURPOSE: Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant malignancies and nephrectomy, isolated or combined with systemic chemotherapy typically has limited or no effectiveness. We report our initial results in patients treated with the association of molecular targeted therapy, nephrectomy, and hybrid dendritic-tumor cell (DC) vaccine. MATERIALS AND METHODS: Two male patients diagnosed with metastatic RCC were selected for the study. They were treated with the triple strategy, in which sunitinib (50 mg per day) was given for 4 weeks, followed by radical nephrectomy after two weeks. DC vaccine was initiated immediately after surgery and repeated monthly. Sunitinib was restarted daily after 2 to 3 weeks of surgery with a 7-day interval every 4 weeks. RESULTS: Both patients had complete adherence to the proposed treatment with DC vaccine therapy combined with sunitinib. Follow-up in these patients at 9 and 10 months demonstrated a stable disease in both, as shown by imaging and clinical findings, with no further treatment required. CONCLUSION: The immune response obtained with DC vaccine combined with the antiangiogenic effect of sunitinib and the potential benefits of cytoreductive nephrectomy in advanced disease could represent a new option in the treatment of metastatic RCC. Further prospective trials are needed not only to elucidate the ideal dosing and schedule, but also to better define the proof-of-concept proposed in this report and its role in clinical practice

Evaluation of Ar, Ar-v7, and P160 Family as Biomarkers for Prostate Cancer: Insights Into the Clinical Significance and Disease Progression

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p \u3c 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p \u3c 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p \u3c 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p \u3c 0.0005), with a shorter time-to-recurrence in the super-expression group (p \u3c 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools