Identification of Plant Viruses Infecting Pear Using RNA Sequencing.

Asian pear (Pyrus pyrifolia) is a widely cultivated and commercially important fruit crop, which is occasionally subject to severe economic losses due to latent viral infections. Thus, the aim of the present study was to examine and provide a comprehensive overview of virus populations infecting a major pear cultivar ('Singo') in Korea. From June 2017 to October 2019, leaf samples (n = 110) of pear trees from 35 orchards in five major pear-producing regions were collected and subjected to RNA sequencing. Most virus-associated contigs matched the sequences of known viruses, including apple stem grooving virus (ASGV) and apple stem pitting virus (ASPV). However, some contigs matched the sequences of apple green crinkle-associated virus and cucumber mosaic virus. In addition, three complete or nearly complete genomes were constructed based on transcriptome data and subjected to phylogenetic analyses. Based on the number of virus-associated reads, ASGV and ASPV were identified as the dominant viruses of 'Singo.' The present study describes the virome of a major pear cultivar in Korea, and looks into the diversity of viral communities in this cultivar. This study can provide valuable information on the complexity of genetic variability of viruses infecting pear trees.

Optimal treatment for penile verrucous carcinoma: a systematic literature review.

BACKGROUND: Verrucous carcinoma, a rare low-grade well-differentiated squamous cell carcinoma, is known for its favorable biological behavior and lack of metastatic potential. However, aggressive resection is problematic in terms of compromised function and aesthetics. Hence, more conservative treatments are needed. METHODS: To identify the up-to-date general biological behavior, diagnosis, and treatment trends, we searched PubMed using the keyword "penile verrucous carcinoma" without restrictions on publication date. RESULTS: Current treatments for penile verrucous carcinoma include wide surgical excision, seldom preventive lymphadenectomy, and conservative chemotherapy without surgery or local excision with safe margins. Despite the advent of partial penectomy to minimally impact function and aesthetics, affected patients experience psychosexual problems. Local excision can be used to save the penile shaft and glans penis without preventive lymphadenectomy or adjuvant therapy and can achieve good clinical prognosis with rare recurrence. CONCLUSIONS: To preserve the functional and cosmetic aspects, we recommend local excision, especially for tumors measuring < 3 cm and classified as stage T1 according to the 2016 tumor node metastasis clinical and pathological classification for penile cancer.

Effects of Variant Histology on the Oncologic Outcomes of Patients With Upper Urinary Tract Carcinoma After Radical Nephroureterectomy: A Propensity Score-Matched Analysis.

PURPOSE: To determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU). PATIENTS AND METHODS: The data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes. RESULTS: UTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P = .011, P = .002, P = .006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR) = 1.92; 95% confidence interval (CI), 1.27-2.89; P = .002], CSS (HR = 4.47; 95% CI, 1.99-10.1; P = .001), and OS (HR = 3.00; 95% CI, 1.55-5.78; P = .001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P = .562, P = .060, P = .153, respectively). CONCLUSION: UTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients.

The current status of hormone treatment for prostate cancer patients in Korean real-world practice: a multi-institutional observational study.

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.

The Case of Huge Pure Lipoma of the Spermatic Cord Misdiagnosed as Inguinal Hernia.

Clinically, pure spermatic-cord lipoma has not been recognized as a disease entity but regarded as an incidental finding at the time of hernia repair, because it presents groin symptoms and clinical findings indistinguishable from those of inguinal hernia. We report the successful treatment of case of huge pure spermatic-cord lipoma originally misdiagnosed as inguinal hernia. The patients had tumor excision without orchiectomy. Symptoms improved without any complication. In patients with inguinal hernia symptoms, pure spermatic-cord lipoma should be recognized as a significant clinical entity, and differential diagnosis should be achieved using ultrasonography and computed tomography to avoid unnecessary hernia repair.

Local Excision for the Treatment of Penile Verrucous Carcinoma.

Penile verrucous carcinoma is known for its favorable biologic behavior and lack of metastatic potential. For preservation of function, treatment has been focused on partial penectomy. Despite partial penectomy for preservation of minimal functional and aesthetic aspects, patients have experienced psychosexual problems. A 73-year-old man had a cauliflower-like verrucous carcinoma on the penile glans and coronary sulcus diagnosed by using excisional biopsy. He underwent degloving excision to save the penile shaft and glans penis. Surgical margin was 3 mm. He had been tumor-free at the 2-year follow-up. For maximum preservation of the functional and aesthetic aspects, we recommend degloving excision.

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study.

PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.

Combination of AG490, a Jak2 inhibitor, and methylsulfonylmethane synergistically suppresses bladder tumor growth via the Jak2/STAT3 pathway.

Human urinary bladder cancer is the fifth most common cancer, with a worldwide estimate of about two million patients. Recurrence after complete transurethral prostatic resection is the most important problem in therapy. Combination therapy is a new approach in the treatment of cancers that do not respond to current therapies. These therapies have many advantages over conventional therapies, such as fewer side-effects and greater efficiency. Research efforts using natural compounds for the elimination or growth suppression of the cancer arise from studies on methylsulfonylmethane (MSM). MSM is a natural sulfur compound with no side-effects. AG490 is a tyrosine kinase inhibitor that has been extensively used for inhibiting Jak2 in vitro and in vivo. In our study, the combinatorial effect of these two agents on human bladder cancer cell lines and xenografts was analyzed. We observed that the combination of AG490 and MSM inhibited cancer cell viability and cell migration in vitro. This combination inhibited VEGF mRNA expression in bladder cancer cell lines. In vivo experiments showed that oral administration of AG490 and MSM combination significantly inhibited the growth of tumor xenografts in mice. Our study clearly demonstrates that the predominant effect of this combination is the reduction of signaling molecules including STAT3, STAT5b, IGF-1R, VEGF and VEGF-R2 which are involved in the growth, progression and metastasis of human bladder cancer. The anti-metastatic ability of this drug combination is confirmed using metastatic animal models. Therefore, this combination could have the effect of genesistasis and powerful anticancer effects against bladder cancer.

Does phosphorylation of cofilin affect the progression of human bladder cancer?

BACKGROUND: We determined the differently expressed protein profiles and their functions in bladder cancer tissues with the aim of identifying possible target proteins and underlying molecular mechanisms for taking part in their progression. METHODS: We examined the expression of proteins by proteomic analysis and western blot in normal urothelium, non-muscle-invasive bladder cancers (NMIBCs), and muscle-invasive bladder cancers (MIBCs). The function of cofilin was analyzed using T24 human bladder cancer cells. RESULTS: The expression levels of 12 proteins were altered between bladder cancers and normal bladder tissues. Of these proteins, 14-3-3σ was upregulated in both NMIBCs and MIBCs compared with controls. On the other hand, myosin regulatory light chain 2, galectin-1, lipid-binding AI, annexin V, transthyretin, CARD-inhibitor of NF-κB-activating ligand, and actin prepeptide were downregulated in cancer samples. Cofilin, an actin-depolymerizing factor, was prominent in both NMIBCs and MIBCs compared with normal bladder tissues. Furthermore, we confirmed that cofilin phosphorylation was more prominent in MIBCs than in NMIBCs using immunoblotting and immunohistochemcal analyses. Epidermal growth factor (EGF) increased the phosphorylation of cofilin and elevated the migration in T24 cells. Knockdown of cofilin expression with small interfering RNA attenuated the T24 cell migration in response to EGF. CONCLUSIONS: These results demonstrate that the increased expression and phosphorylation of cofilin might play a role in the occurrence and invasiveness of bladder cancer. We suspected that changes in cofilin expression may participate in the progression of the bladder cancer.

Effect of Intravesical Prostatic Protrusion on the Characteristics of Lower Urinary Tract Symptom Change after 12-Week Drug Medication: A Prospective Analysis.

OBJECTIVES: The aim of this study was to identify whether intravesical prostatic protrusion (IPP) is related to the characteristics of voiding symptoms improvement after drug treatment in benign prostatic hyperplasia patients. METHODS: Ninety male patients with more than 30 g prostate volume were prospectively enrolled. All patients were evaluated with International Prostate Symptoms Score (IPSS), uroflowmetry, postvoid residual urine (PVR), prostate volume and IPP measurement by transrectal ultrasound. Treatment response was evaluated again by IPSS after 12 weeks of medication. We evaluated the correlation of IPP and IPSS, quality of life (QoL) score, maximum urinary flow rate (Qmax) and PVR, and compared IPPS and IPSS subscale score change between the IPP and non-IPP groups. RESULTS: IPP was significantly correlated with total IPSS, voiding/storage symptom subscore and PVR. IPP was inversely correlated with Qmax. IPP showed a significant correlation with storage symptoms after an adjustment of prostate volume. After 12 weeks of medication, the IPP group showed persistently high storage symptoms than the non-IPP group. CONCLUSION: BPH patients with IPP showed less improvement of storage symptoms after 12 weeks of medication. This study suggests that IPP may be a possible cause of intractable storage symptoms in early treatment.

Isolation and characterization of smooth muscle cells from rat corpus cavernosum tissue for the study of erectile dysfunction.

PURPOSE: Primary culture of the cavernous smooth muscle cells from corpus cavernous tissues is known to be difficult, mainly because of contamination with fibroblasts. We applied a new method for better isolation of rat penile smooth muscle cells (RPSMCs) from rat corpus cavernosum tissue for reliable ex vivo research on erectile dysfunction. MATERIALS AND METHODS: With the use of 8-week-old adult male Sprague-Dawley rats, ex vivo migrations of rat cavernous tissue were measured by penis and aortic ring assay by use of a Matrigel-based D-valine-modified culture method. The expression of α-smooth muscle actin (α-SMA) and platelet/endothelial cell adhesion molecule (PECAM)-1 in the RPSMCs was determined by standard immunofluorescent staining and immunoblotting. The expression patterns of phosphodiesterase (PDE) family mRNA in RPSMCs were compared with patterns in rat aortic smooth muscle cells (RASMCs) by use of quantitative real-time reverse transcription polymerase chain reaction. RESULTS: Immunocytochemical staining showed greater α-SMA-positive and PCAM-1-negative fluorescence. Moreover, whereas the expression of α-SMA was detected in the RPSMCs, that of PECAM-1 was not. The levels of PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, and PDE5A mRNA in the RPSMCs were about 3.2-, 4.4-, 3.4-, 29.0-, 3.5-, 2.8-, 2.9-, 6.1-, 45.0-, and 6.0-fold the corresponding expression in RASMCs. CONCLUSIONS: We developed a two-stage tissue culture method utilizing a Matrigel-based sprouting culture system to facilitate stromal cell sprouting and an adherent culture system using D-valine to eliminate the contamination of fibroblasts into the smooth muscle cells.

Current status of transurethral prostatectomy: a korean multicenter study.

PURPOSE: We aimed to verify the current status of transurethral resection of the prostate (TURP) in Korea. MATERIALS AND METHODS: The medical records of 1,341 men who underwent TURP in 9 Korean medical centers between 2004 and 2008 were reviewed. The patients were divided into two groups according to time periods: 2004-2005 (group 1) and 2006-2008 (group 2). To verify differences in the two patient groups, age, prostate volume, indications for TURP, preoperative International Prostate Symptom Score (IPSS), and resected tissue weight were evaluated. RESULTS: The mean age of the patients was 71.2 years and the mean IPSS was 22.7. The patients' characteristics were not significantly different between the two groups. The annual cases of TURP increased over the study period. The proportion of lower urinary tract symptoms (LUTS) as an indication for TURP increased up to 58.3% in group 2 compared with 51.6% in group 1 (p=0.019). However, the proportion of patients who presented with acute urinary retention decreased from 35.5% to 30.3% with marginal statistical significance (p=0.051). Other indications such as hematuria, bladder stone, recurrent urinary tract infection, and hydronephrosis were not significantly different between the groups. The mean resected weights of the prostate were similar (17.5 g in group 1 and 18.3 g in group 2, respectively; p>0.05). CONCLUSIONS: TURP has been steadily performed in patients with benign prostatic hyperplasia and it is expected to remain constant. LUTS was the most common indication for TURP in recent years.

The contribution of abdominal obesity and dyslipidemia to metabolic syndrome in psychiatric patients.

BACKGROUND/AIMS: Metabolic syndrome is an emerging risk factor for cardiovascular disease. This study investigated the prevalence of metabolic syndrome among psychiatric patients in order to identify the dominant factors of metabolic syndrome. METHODS: We enrolled 225 patients who had been admitted to a chronic psychiatric hospital from October 2005 to February 2006. The prevalence of metabolic syndrome was assessed based on the Adult Treatment Panel (ATP)-III with the new criterion of waist circumference in the Asia-Pacific Region. RESULTS: The study population was relatively young (41.1 +/- 8.8 years) and obese (waist in men, 91.3 +/- 9.2 cm; waist in women, 84.1 +/- 8.8 cm). Sixty percent of patients met the waist criterion of metabolic syndrome and 56% met the low high density lipoprotein (HDL) criterion. The mean serum triglycerides were high (170.0 +/- 119.7 mg/dL) and 46% of patients met the triglyceride criterion. In contrast, less than 10% of patients showed impaired fasting glucose or high blood pressure (5%, 9%, respectively). The overall prevalence of metabolic syndrome was 34.2% by applying ATP-III criteria (40% in men and 20% in women, respectively). No specific anti-psychotic drugs were related to significant increase in the incidence of metabolic syndrome. CONCLUSIONS: Abdominal obesity and dyslipidemia (low HDL and high triglycerides) were dominant contributing factors of metabolic syndrome among psychiatric patients, and the affected age groups were relatively young. These findings indicate that active and early screening, including triglycerides, HDL, and waist measurement, are absolutely essential to managing metabolic syndrome in psychiatric patients.

Clinical implication of serum C-reactive protein in patients with uncomplicated acute pyelonephritis as marker of prolonged hospitalization and recurrence.

OBJECTIVES: To analyze the clinical value of C-reactive protein (CRP) as a marker of prolonged hospitalization and a predictor of recurrence in patients after uncomplicated acute pyelonephritis (APN). METHODS: A total of 202 consecutive adult patients with APN were prospectively enrolled from September 2005 to June 2007. APN was defined as the concomitant presence of 4 major and >/=2 minor clinical or laboratory signs or symptoms suggestive of APN. All patients were treated with parenteral antibiotics. The patients were discharged after normalization of body temperature, serum white blood cell counts, and urinalysis. Correlations among the recurrence of APN and various factors, including CRP, were investigated. RESULTS: Of the 202 patients, 13 were excluded because of the presence of complicating factors or insufficient data. APN recurrence developed in 4 patients (2.1%). The CRP level at discharge correlated significantly with the recurrence of APN on univariate and multivariate analysis. Irrespective of the normalization of body temperature, serum white blood cell counts, and urinalysis, the recurrence of APN was significantly greater in the patients with CRP >4 mg/dL than in those with <4 mg/dL at discharge. Patients with a maximal CRP of >15 mg/dL during admission had a longer hospitalization and required more intravenous antibiotic therapy than did the patients with a maximal CRP of <15 mg/dL. CONCLUSIONS: As a marker of prolonged hospitalization and recurrence, CRP can complement the present clinical and laboratory parameters used as guides in the proper treatment of patients with uncomplicated APN.

A multi-institutional study on histopathological characteristics of surgically treated renal tumors: the importance of tumor size.

PURPOSE: The incidence of accidentally detected small renal tumors is increasing throughout the world. In this multi-institutional study performed in Korea, histopathological characteristics of contemporarily surgically removed renal tumors were reviewed with emphasis on tumor size. MATERIALS AND METHODS: Between January 1995 and May 2005, 1,702 patients with a mean age of 55 years underwent surgical treatment at 14 training hospitals in Korea for radiologically suspected malignant renal tumors. Clinicopathological factors and patient survival were analyzed. RESULTS: Of the 1,702 tumors, 91.7% were malignant and 8.3% were benign. The percentage of benign tumors was significantly greater among those < or = 4 cm (13.2%) than those > 4 cm (4.5%) (p < 0.001). Among renal cell carcinoma patients, the percentage of tumors classed as stage > or = T3 was significantly less among tumors < or = 4 cm (5.2%) than those > 4 cm (26.8%) (p < 0.001). The percentage of tumors classed as Fuhrman's nuclear grades > or = 3 was also significantly less among tumors < or = 4 cm (27.3%) than tumors > 4 cm (50.9%) (p < 0.001). The 5-year cancer-specific survival rate was 82.7%, and T stage (p < 0.001), N stage (p < 0.001), M stage (p = 0.025), and Fuhrman's nuclear (p < 0.001) grade were the only independent predictors of cancer-specific survival. CONCLUSION: In renal tumors, small tumor size is prognostic for favorable postsurgical histopathologies such as benign tumors, low T stages, and low Fuhrman's nuclear grades. Our observations are expected to facilitate urologists to adopt function-preserving approach in the planning of surgery for small renal tumors with favorable predicted outcomes.

Laparoscopic management of complicated urachal remnant in a child.

A few cases of laparoscopic surgery for urachal remnant in children has been reported in English literature. With recent developments in minimal invasive surgery, laparoscopic approach for urachal remnant in adulthood is recommended by some laparoscopic surgeons because of its technical feasibility and safety as well as cosmesis. Recently we experienced a case of complicated urachal remnant in a 14-month-old girl, who was managed by laparoscopic approach. At presentation, she complained of high fever and lower urinary tract symptoms. After 6 weeks of antibiotics therapy, laparoscopic surgery was performed transperitoneally via 3 ports. Our experience suggests that laparoscopic excision of urachal remnant can be performed easily and safely in children.

Detection rate of prostate cancer on biopsy according to serum prostate-specific antigen in Korean men: a multicenter study.

OBJECTIVES: To evaluate the detection rate of prostate cancer on biopsy according to the serum prostate-specific antigen (PSA) level in Korean men and compare the detection rate with those of Japanese and American men in other studies. METHODS: We retrospectively analyzed 2422 Korean men who had undergone prostate biopsy at 12 medical centers from 1993 to 2002. In the case of a PSA level greater than 4.0 ng/mL or abnormal digital rectal examination findings, prostate biopsy was performed. RESULTS: Of the 2422 men, 962 (39.7%) were diagnosed with prostate cancer. With PSA levels between 4.0 and 10.0 ng/mL, the detection rate of prostate cancer was 15.9%. This rate was similar to that of Japanese men (15.8%), but lower than that of American men (25%). In the cases with a PSA level greater than 10.0 ng/mL, the detection rate for Korean and Japanese men was 59.5%, and was also lower than the 67% rate for American men. When serum PSA levels were divided into five subgroups (less than 4.0, 4.0 to 10.0, 10.0 to 20.0, 20.0 to 100.0, and greater than 100.0 ng/mL), the detection rate of prostate cancer was 12.4%, 15.9%, 34.1%, 66.2%, and 93.8%, respectively. CONCLUSIONS: In Korean men, the detection rate of prostate cancer on biopsy according to serum PSA level appears to be comparable to that for Japanese men and lower than that for American men.

Molecular signaling cascade in DNA bisintercalator, echinomycin-induced apoptosis of HT-29 cells: evidence of the apoptotic process via activation of the cytochrome c-ERK-caspase-3 pathway.

The DNA-interactive drug, echinomycin, is a potent antitumor agent, which is able to induce apoptosis in a multitude of cancer cell lines. Previously, we showed that echinomycin strongly inhibited the growth of a variety of cancer cell lines, and the activation of mitogen-activated protein kinases (MAPK) in human colon cancer cells (HT-29). However, little information currently exists regarding the details of intracellular signaling pathways such as the MAPK, mitochondrial, and caspase pathways. In order to clarify this issue, we verified the plausible molecular signaling cascade by performing an immunobiochemical apoptosis experiment involving the mitochondrial and caspase pathways. The apoptotic process of HT-29 cells was accompanied by the activation of procaspase-9, -3 and cytochrome c release. Both caspase and MAPK inhibitors were used in the determination of the specific roles of MAPK and caspase in echinomycin-induced apoptosis. ERK (PD98059) or caspase-3-specific (Z-DEVD-FMK) inhibitors were discovered to significantly attenuate echinomycin-induced apoptosis. PD98059 treatment or overexpression of kinase-inactive ERK did not alter the echinomycin-induced cytochrome c release into the cytosol, but did diminish the activation of procaspase-3. Also, Z-DEVD-FMK was found to have no effect on either cytochrome c release or ERK activation. Taken together, these results indicate that cytochrome c release, and the activation of ERK and caspase-3 in the final apoptosis pathway are all relevant factors in echinomycin-induced apoptosis. To our knowledge, this study is the first to delineate the echinomycin's direct detrimental effects on colon cancer cells.