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Several marine drugs exert anticancer effects by inducing oxidative stress, which becomes overloaded and kills cancer cells when redox homeostasis is imbalanced. The downregulation of antioxidant signaling induces oxidative stress, while its upregulation attenuates oxidative stress. Marine drugs have miRNA-modulating effects against cancer cells. However, the potential antioxidant targets of such drugs have been rarely explored. This review aims to categorize the marine-drug-modulated miRNAs that downregulate their antioxidant targets, causing oxidative stress in anticancer treatments. We also categorize the downregulation of oxidative-stress-inducing miRNAs in antioxidant protection among non-cancer cells. We summarize the putative antioxidant targets of miRNA-modulating marine drugs by introducing a bioinformatics tool (miRDB). Finally, the marine drugs affecting antioxidant targets are surveyed. In this way, the connections between marine drugs and their modulating miRNA and antioxidant targets are innovatively categorized to provide a precise network for exploring their potential anticancer functions and protective effects on non-cancer cells.
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Antineoplásicos , Antioxidantes , MicroRNAs , Estresse Oxidativo , Transdução de Sinais , MicroRNAs/metabolismo , MicroRNAs/genética , Antioxidantes/farmacologia , Antineoplásicos/farmacologia , Humanos , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Organismos AquáticosRESUMO
Ferroptosis, which comprises iron-dependent cell death, is crucial in cancer and non-cancer treatments. Exosomes, the extracellular vesicles, may deliver biomolecules to regulate disease progression. The interplay between ferroptosis and exosomes may modulate cancer development but is rarely investigated in natural product treatments and their modulating miRNAs. This review focuses on the ferroptosis-modulating effects of natural products and miRNAs concerning their participation in ferroptosis and exosome biogenesis (secretion and assembly)-related targets in cancer and non-cancer cells. Natural products and miRNAs with ferroptosis-modulating effects were retrieved and organized. Next, a literature search established the connection of a panel of ferroptosis-modulating genes to these ferroptosis-associated natural products. Moreover, ferroptosis-associated miRNAs were inputted into the miRNA database (miRDB) to bioinformatically search the potential targets for the modulation of ferroptosis and exosome biogenesis. Finally, the literature search provided a connection between ferroptosis-modulating miRNAs and natural products. Consequently, the connections from ferroptosis-miRNA-exosome biogenesis to natural product-based anticancer treatments are well-organized. This review sheds light on the research directions for integrating miRNAs and exosome biogenesis into the ferroptosis-modulating therapeutic effects of natural products on cancer and non-cancer diseases.
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Produtos Biológicos , Exossomos , Ferroptose , MicroRNAs , Neoplasias , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Humanos , Exossomos/metabolismo , Exossomos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , AnimaisRESUMO
Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.
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Protein phosphatase 2A (PP2A), a heterotrimeric holoenzyme (scaffolding, catalytic, and regulatory subunits), regulates dephosphorylation for more than half of serine/threonine phosphosites and exhibits diverse cellular functions. Although several studies on natural products and miRNAs have emphasized their impacts on PP2A regulation, their connections lack systemic organization. Moreover, only part of the PP2A family has been investigated. This review focuses on the PP2A-modulating effects of natural products and miRNAs' interactions with potential PP2A targets in cancer and non-cancer cells. PP2A-modulating natural products and miRNAs were retrieved through a literature search. Utilizing the miRDB database, potential PP2A targets of these PP2A-modulating miRNAs for the whole set (17 members) of the PP2A family were retrieved. Finally, PP2A-modulating natural products and miRNAs were linked via a literature search. This review provides systemic directions for assessing natural products and miRNAs relating to the PP2A-modulating functions in cancer and disease treatments.
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Produtos Biológicos , MicroRNAs , Neoplasias , Proteína Fosfatase 2 , MicroRNAs/metabolismo , MicroRNAs/genética , Proteína Fosfatase 2/metabolismo , Produtos Biológicos/farmacologia , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , AnimaisRESUMO
The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow-Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells.
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Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.
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Cisplatino , Neoplasias da Bexiga Urinária , Humanos , Espécies Reativas de Oxigênio/metabolismo , Cisplatino/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose , Antioxidantes/farmacologia , Dano ao DNA , Caspases/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Poli(ADP-Ribose) Polimerases/farmacologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genéticaRESUMO
BACKGROUND: Radical prostatectomy has become the gold standard for treating localized prostate cancer. Improvement in the single-site technique and surgeon's skill reduces not only the hospital duration but also the number of wounds. Realizing the learning curve for a new procedure can prevent unnecessary mistakes. OBJECTIVE: To analyze the learning curve of extraperitoneal laparoendoscopic single-site robot-assisted radical prostatectomy (LESS-RaRP). METHODS: We retrospectively evaluated 160 patients diagnosed with prostate cancer during June 2016 to December 2020 who underwent extraperitoneal LESS-RaRP. Calculated cumulative sum analysis (CUSUM) was used to evaluate the learning curves for the extraperitoneal setting time, robotic console time, total operation time, and blood loss. The operative and functional outcomes were also assessed. RESULTS: The learning curve of the total operation time was observed in 79 cases. For the extraperitoneal setting and robotic console times, the learning curve was observed in 87 and 76 cases, respectively. The learning curve for blood loss was observed in 36 cases. No in-hospital mortality or respiratory failure was observed. CONCLUSION: Extraperitoneal LESS-RaRP using the da Vinci Si system is safe and feasible. Approximately 80 patients are required to achieve a stable and consistent operative time. A learning curve for blood loss was observed after 36 cases.
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Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Curva de Aprendizado , Estudos Retrospectivos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Laparoscopia/métodos , Resultado do TratamentoRESUMO
Excavatolide C (EXCC) is a bioactive compound derived from the gorgonian octocoral Briareum excavatum, and its anticancer effects are rarely addressed, particularly for bladder cancer. This investigation aimed to explore the potential impacts of EXCC on inhibiting the proliferation of three kinds of bladder cancer cells (5637, BFTC905, and T24). EXCC inhibits bladder cancer cell proliferation based on 48 h ATP assay. This antiproliferation function is validated to be oxidative stress dependent. Cellular and mitochondrial oxidative stresses were upregulated by EXCC, accompanied by depleting glutathione and mitochondrial membrane potential. These antiproliferation and oxidative stress events were suppressed by N-acetylcysteine (NAC), indicating that EXCC has an oxidative stress-regulating function for antiproliferation of bladder cancer cells. Oxidative stress-related responses such as apoptosis, caspase activation, and DNA damage were upregulated by EXCC and reverted by NAC. Taken together, the antiproliferation function of EXCC provides a potential treatment against bladder cancer cells via oxidative stress modulation.
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BACKGROUND/PURPOSE: Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC who underwent radical nephroureterectomy (RNU). METHODS: Patients who underwent RNU for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan-Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages. RESULTS: A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan-Meier analysis revealed no differences between sexes on recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer RFS. After adjusting for renal function, the analysis found men had worse RFS. CONCLUSION: The female sex is significantly associated with a higher prevalence of advanced CKD stage, and dialysis among patients with UTUC who underwent RNU in our institute. Sex differences in renal function needs to be considered when evaluating survival.
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Carcinoma de Células de Transição , Insuficiência Renal Crônica , Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Carcinoma de Células de Transição/cirurgia , Feminino , Humanos , Rim/patologia , Rim/fisiologia , Masculino , Nefroureterectomia/métodos , Prognóstico , Estudos Retrospectivos , Caracteres Sexuais , Neoplasias da Bexiga Urinária/patologia , Neoplasias Urológicas/patologia , Neoplasias Urológicas/cirurgiaRESUMO
This study aimed to examine the prognostic significance of preoperative inflammation-associated blood cell markers in the metachronous contralateral recurrence of upper tract urothelial carcinoma (UTUC). Patients with nonmetastatic UTUC treated in Taiwan and the U.S. between 1990 and 2017 were included. The Kaplan-Meier method was used to calculate the contralateral recurrence rate, and multivariate logistic regression was performed to study the association of blood cell markers and clinicopathological characteristics with contralateral recurrence. Overall, a total of 1039 patients were included in this study, 52 of whom (5.0%) developed metachronous recurrence of the contralateral side. Kaplan-Meier analysis indicated that a history of bladder cancer (p = 0.006), multiple tumors (p = 0.016), advanced chronic kidney disease (CKD; p < 0.001), elevated serum white blood cell (WBC) count (p < 0.001), and decreased hemoglobin levels (p = 0.001) significantly reduced the contralateral recurrence-free survival. Multivariate analysis showed that multiple tumors (hazard ratio (HR), 1.87; p = 0.030), advanced CKD (HR, 2.63; p = 0.002) and increased WBC count (HR, 2.60; p = 0.001) were independent risk factors for higher contralateral recurrence rate. Notably, advanced CKD was a significant factor regardless of the patient's region. In summary, multiple tumors, advanced CKD and elevated serum WBC count are independent predictors of contralateral recurrence in patients with UTUC. It is recommended that patients with these adverse characteristics be closely followed up to monitor the opposite upper urinary tract.
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BACKGROUND: This study aimed to assess the prognostic significance of pre-treatment lymphocyte-related systemic inflammatory biomarkers in upper tract urothelial carcinoma (UTUC) patients. METHODS: This study included non-metastatic UTUC patients treated at our hospital between 2001 and 2013. The receiver operating characteristic curve was used to obtain the optimal neutrophile-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Multivariate logistic regression was performed to investigate the relationship between NLR, PLR, and SII and clinical pathologic characteristics. The Kaplan-Meier method was used to calculate the metastasis-free survival (MFS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS), and the log-rank test was used to compare the survival rate. RESULTS: Overall, 376 patients were included in the current study. An elevated SII was associated with symptomatic hydronephrosis, bladder cancer history, advanced pathologic tumor stage, lymph node invasion, adjuvant chemotherapy and concomitant carcinoma in situ (CIS); high NLR was associated with older age, symptomatic hydronephrosis, hemodialysis status, anemia, multifocal tumor, advanced pathologic tumor stage, and adjuvant chemotherapy; and high PLR was associated with older age, anemia, advanced pathologic tumor stage, and adjuvant chemotherapy. The Kaplan-Meier analysis indicated that patients exhibiting higher NLR, PLR, and SII showed significantly poor MFS and CSS rates. Only high SII showed significantly worse BRFS rates. CONCLUSIONS: The NLR, PLR, and SII were independent predictive factors for both MFS and CSS in UTUC patients. Among the factors, only elevated SII can predict bladder recurrence. Therefore, the patients might need close bladder monitoring during the follow-up.
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Ethyl acetate Nepenthes extract (EANT) from Nepenthes thorellii × (ventricosa × maxima) shows antiproliferation and apoptosis but not necrosis in breast cancer cells, but this has not been investigated in oral cancer cells. In the present study, EANT shows no cytotoxicity to normal oral cells but exhibits selective killing to six oral cancer cell lines. They were suppressed by pretreatment of the antioxidant inhibitor N-acetylcysteine (NAC), demonstrating that EANT-induced cell death was mediated by oxidative stress. Concerning high sensitivity to EANT, Ca9-22 and CAL 27 oral cancer cells were chosen for exploring detailed selective killing mechanisms. EANT triggers a mixture of necrosis and apoptosis as determined by annexin V/7-aminoactinmycin D analysis. Still, they show differential switches from necrosis at a low (10 µg/mL) concentration to apoptosis at high (25 µg/mL) concentration of EANT in oral cancer cells. NAC induces necrosis but suppresses annexin V-detected apoptosis in oral cancer cells. Necrostatin 1 (NEC1), a necroptosis inhibitor, moderately suppresses necrosis but induces apoptosis at 10 µg/mL EANT. In contrast, Z-VAD-FMK, a pancaspase inhibitor, slightly causes necrosis but suppresses apoptosis at 10 µg/mL EANT. Furthermore, the flow cytometry-detected pancaspase activity is dose-responsively increased but is suppressed by NAC and ZVAD, although not for NEC1 in oral cancer cells. EANT causes several oxidative stress events such as reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization. In response to oxidative stresses, the mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), heme oxygenase 1 (HMOX1), and thioredoxin (TXN), are overexpressed in oral cancer cells. Moreover, EANT also triggers DNA damage, as detected by γH2AX and 8-oxo-2'-deoxyguanosine adducts. The dependence of oxidative stress is validated by the evidence that NAC pretreatment reverts the changes of cellular and mitochondrial stress and DNA damage. Therefore, EANT exhibits antiproliferation involving an oxidative stress-dependent necrosis/apoptosis switch and DNA damage in oral cancer cells.
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Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.
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Currently, over 80% of radical prostatectomies have been performed with the da Vinci Surgical System. In order to improve the aesthetic outlook and decrease the morbidity of the operation, the new da Vinci Single Port (SP) system was developed in 2018. However, one major problem is the SP system is still not available in most countries. We aim to present our initial experience and show the safety and feasibility of the single-site robotic-assisted radical prostatectomy (LESS-RP) using the da Vinci Single-Site platform. From June 2017 to January 2020, 120 patients with localized prostate cancer (stage T1-T3b) at Kaohsiung Medical University Hospital were included in this study. We describe our technique and report our initial results of LESS-RP using the da Vinci Si robotic system. Preoperative, intraoperative and postoperative patient variables were recorded. Prostate-specific antigen (PSA)-free survival was also analyzed. A total of 120 patients were enrolled in the study. The median age of patients was 68 years (IQR 63-71), with a median body mass index of 25 kg/m2 (IQR 23-27). The median PSA value before operation was 10.7 ng/mL (IQR 7.9-21.1). The median setup time for creat-ing the extraperitoneal space and ports document was 25 min (IQR 18-34). The median robotic console time and operation time were 135 min (IQR 110-161) and 225 min (IQR 197-274), respectively. Median blood loss was 365 mL (IQR 200-600). There were 11 (9.2%) patients who experienced complications (Clavien-Dindo classification Gr II). The me-dian catheter duration was 8 days (IQR 7-9), with a median of 10 days (IQR 7-11) of hospital stay. The PSA free-survival rate was 86% at a median 19 months (IQR 6-28) of follow up. Robotic radical prostatectomy using the da Vinci Single-Site platform system is safe and feasible, with acceptable outcomes.
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PURPOSE: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC. METHODS: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity. RESULTS: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients. CONCLUSION: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.
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Asiático , Índice de Massa Corporal , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Nefroureterectomia , Obesidade/complicações , Neoplasias Ureterais/complicações , Neoplasias Ureterais/cirurgia , População Branca , Idoso , Carcinoma de Células de Transição/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Ureterais/mortalidadeRESUMO
We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p < 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p < 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121-1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169-2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095-1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141-1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.
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Partial nephrectomy (PN) is the standard procedure for most patients with localized renal cancer. Laparoscopy has become the preferred surgical approach to target this cancer, but the steep learning curve with laparoscopic PN (LPN) remains a concern. In LPN intracorporeal suturing, the operation time is further extended even under robot assistance, a step which prolongs warm ischemic time. Herein, we shared our experience to reduce the warm ischemia time, which allows surgeons to perform LPN more easily by using a combination of hemostatic agents to safely control parenchymal bleeding. Between 2015 and 2018, we enrolled 52 patients who underwent LPN in our hospital. Single-site sutureless LPN and traditional suture methods were performed in 33 and 19 patients, respectively. Preoperative, intra-operative, and postoperative variables were recorded. Renal function was evaluated by estimated glomerular filtration rate (eGFR) pre- and postoperatively. The average warm ischemia time (sutureless vs. suture group; 11.8 ± 3.9 vs. 21.2 ± 7.2 min, p < 0.001) and the operation time (167.9 ± 37.5 vs. 193.7 ± 42.5 min, p = 0.035) were significantly shorter in the sutureless group. In the sutureless group, only 2 patients suffered from massive urinary leakage (>200 mL/day) from the Jackson Pratt drainage tube, but the leakage spontaneously decreased within 7 days after surgery. eGFR and serum hemoglobin were not found to be significantly different pre- and postoperatively. All tumors were removed without a positive surgical margin. All patients were alive without recurrent tumors at mean postoperative follow-ups of 29.3 ± 12.2 months. Single-site sutureless LPN is a feasible surgical method for most patients with small exophytic renal cancer with excellent cosmetic results without affecting oncological results.
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We sought to examine the relationship between microtubule-associated proteins (MAPs) and the prognosis of urothelial carcinoma by assessing the microtubule bundle formation genes using a reappraisal transcriptome dataset of urothelial carcinoma (GSE31684). The result revealed that microtubule-associated protein 1b (MAP1B) is the most significant upregulated gene related to cancer progression. Real-time reverse-transcription polymerase chain reaction was used to measure MAP1B transcription levels in urothelial carcinoma of the upper tract (UTUC) and the bladder (UBUC). Immunohistochemistry was conducted to detect MAP1B protein expression in 340 UTUC and 295 UBUC cases. Correlations of MAP1B expression with clinicopathological status, disease-specific survival, and metastasis-free survival were completed. To assess the oncogenic functions of MAP1B, the RTCC1 and J82 cell lines were stably silenced against their endogenous MAP1B expression. Study findings indicated that MAP1B overexpression was associated with adverse clinical features and could independently predict unfavorable prognostic effects, indicating its theranostic value in urothelial carcinoma.
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PURPOSE: We aimed to identify the effect of preoperative anemia on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) who had different levels of renal function. METHODS: Between 2000 and 2013, we enrolled 370 patients who underwent radical nephroureterectomy for nonmetastatic UTUC. Preoperative anemia was defined as hemoglobin <130g/l in men and <120g/l in women based on the World Health Organization classification. Kaplan-Meier method was applied to estimate the effect anemia on survival, and hazard ratios (HR) of anemia and other clinicopathological parameters were evaluated by Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages. RESULTS: In all, 242 (65.4%) patients were anemic before surgery. Those with preoperative anemia had worse CKD stage (P<0.001) and higher pathological tumor stage (P = 0.023). In univariate analysis, metastasis-free and cancer-specific survival rates were not significantly associated with preoperative anemia (HR = 1.51, 95% CI: 0.93-2.44, P = 0.093 and HR = 1.59, 95% CI: 0.93-2.72, PP = 0.094, respectively). However, in patients without stage 5 CKD, those with preoperative anemia had apparently inferior metastasis-free and cancer-specific survival than those without (HR = 1.88, 95% CI: 1.14-3.01, P = 0.014 and HR = 2.03, 95% CI: 1.16-3.56, P = 0.010, respectively). A multivariate Cox proportional hazards model indicated that preoperative anemia was an independent predictor for both metastasis-free (HR = 2.17, 95% CI: 1.21-3.90, P = 0.010) and cancer-specific survival (HR = 2.21, 95% CI: 1.15-4.21, P = 0.017). CONCLUSIONS: Among patients without stage 5 CKD, preoperative anemia was a significant prognostic factor to predict metastatic progression and cancer-specific death in UTUC following radical nephroureterectomy. It was important to be aware of patients׳ renal function while evaluating the effect of anemia on outcome of UTUC.
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Anemia/complicações , Nefroureterectomia , Neoplasias Urológicas/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: The prevalence of prostate cancer (PCa) has been increasing in recent years. Treatment strategies are largely based on the results of bone scan screening. Therefore, our aim was to investigate predictors of positive bone metastasis in newly diagnosed PCa patients. MATERIALS AND METHODS: After extensive review, 336 consecutive patients newly diagnosed with PCa between April 2010 and November 2013 at our institution were enlisted in the study. Patients were divided into two groups according to bone scan results. Univariate analyses (Chi-square test for discrete variables and independent t-test for continuous variables) were applied to determine the potentially significant risk factors associated with distant bone metastasis. Binary logistic regression analyses were used to further investigate the influence of these factors on bone metastasis. RESULTS: The patient mean age was 71.9 ± 8.6 years (range: 48 to 94 years). The mean prostate specific antigen (PSA) level and biopsy Gleason score were 260.2 ± 1107.8 ng/mL and 7.4 ± 1.5, respectively. The body mass index (BMI) for the series was 24.5 ± 3.4 kg/m2. Sixty-four patients (19.0%) had a positive bone scan result. Patients with positive bone scan results had a significantly lower BMI (23.3 ± 3.5 vs. 24.8 ± 3.3; p=0.003), a higher Gleason score (8.5 ± 1.1 vs. 7.1 ± 1.5; p < 0.001), and a higher PSA level (1071.3 ± 2337.1 vs. 69.4 ± 235.5; p < 0.001) than those without bone metastasis. Multivariate logistic regression analysis employing the above independent predictors demonstrated that a Gleason score of ≥7, clinical stage ≥T3, BMI ≤22 kg/m2, and an initial PSA level of ≥20 ng/mL were all independent predictors of bone metastasis. CONCLUSIONS: A bone scan might be necessary in newly diagnosed PCa patients with any of the following criteria: clinical stage T3 or higher, a Gleason score of 7 or higher, BMI equal to or less than 22, and a PSA level of 20 or higher.