Majority of current treatment strategies against erectile dysfunction (ED) has been consisted of only a supportive care to sustain enough erection during a sexual intercourse. In this study, we ...investigated whether the cultured conditioned medium of human exfoliated deciduous dental pulp stem cells (SHED‐CM) had an ability to treat ED through fundamentally repairing the pathological damage of vascular endothelial cells of the corpus cavernosum. An open‐label pilot study was performed from April 2016 to October 2020. SHED‐CM was injected directly into the corpus cavernosum of penis of 38 ED patients who visited our clinic and fulfilled the inclusion criteria. Efficacy was assessed using the simplified International Index of Erectile Function (IIEF‐5) questionnaire. The average age and initial IIEF‐5 score of the patients enrolled in this study was 56 (31–79) years old and 13.1 (5–20) points, respectively. Medical history revealed 7 patients with diabetes, 7 patients with hypertension and 1 patient with priapism undergone shunt operation. Of these, 37 patients (97.4%) showed an improvement in IIEF‐5 of an average of 19.3 (7–25) points or 64.4 (10–300) % increase after three injections of SHED‐CM. Eighteen patients (47.4%) achieved more than 21 points (no ED) in IIEF‐5. No adverse events were encountered. This is the first clinical report of ED treatment in the literatures evaluating the efficacy of SHED‐CM. Treatment with SHED‐CM is expected to repair vascular damages of the corpus cavernosum, which are the main cause of ED, and to be widely spread as a fundamental clinical application for ED.
Concern about a long-term effect of the delivery of intensity modulated radiation therapy (IMRT) for prostate cancer on serum testosterone levels remains unelucidated. We evaluated how IMRT for ...localized prostate cancer affects serum testosterone levels during a follow-up period of up to 10 years.
We retrospectively evaluated data from 182 patients with localized prostate cancer who underwent definitive IMRT alone between 2007 and 2014. Serum total testosterone (TT) levels were measured by blood draws between 6 AM and 11 AM before treatment and at every posttreatment follow-up for 10 years. Pretreatment values and each posttreatment testosterone value were compared using a Wilcoxon signed rank test. The data set was stratified into 4 groups based on the pretreatment testosterone (pre-TT) values using quartiles.
The median absolute or relative changes in TT levels from pretreatment were –0.42 ng/mL or –12.0% at 3 months after radiation therapy (P < .0001). Subsequently, TT levels gradually recovered to nearly the pretreatment levels 24 to 36 months after IMRT. When analyzed according to the pre-TT quartile, median TT levels initially decreased at the 3- to 12-month period in all the quartiles; however, median TT levels increased from the 18-month period in the first and second quartile groups, whereas they were maintained at less than the pretreatment levels in the third and the fourth quartile groups throughout the entire decade after radiation therapy. The proportion of patients with hypogonadal status, defined as TT levels <3.00 ng/mL, did not increase over time.
A transient and modest decrease of TT levels after IMRT spontaneously recovered to the pretreatment levels at the 24- to 36-month period except in patients in the higher quartile of pre-TT. This might have been partly owing to a variable sensitivity of individual testicular function to scattered radiation. Patients with lower pre-TT did not demonstrate a progressive overall rate of hypogonadism until 10 years after radiation therapy.
Objective: To assess the combination of docetaxel (DTX), estramustine phosphate (EMP) and hydrocortisone for patients with hormone‐refractory prostate cancer (HRPC).
Methods: A total of 63 patients ...with HRPC were treated with a chemotherapeutic regimen including DTX, EMP, and hydrocortisone. Clinical and pathological features were correlated to serum prostate‐specific antigen (PSA) recurrence and survival rates. Incidence and degree of toxicities were also retrospectively reviewed.
Results: A median of 11 courses of chemotherapy was administered per patient. PSA levels decreased by >50% in 32 (51%) patients and >90% in 18 (29%) patients. Median time to PSA progression was 6 months (range from 1 to 41 months) and median time of overall survival was 14 months (range from 1 to 56 months). In a univariate analysis to predict overall survival, PSA, hemoglobin, alkaliphosphatase, and performance status prior to the chemotherapy were significant factors. Despite grade 3–4 neutropenia in 87% of patients, grade 5 interstitial pneumonia in one patient and grade 4–5 myocardial infarction in two patients were recognized, the regimen seemed to be relatively safe.
Conclusions: Combination chemotherapy with DTX, EMP and hydrocortisone provides survival benefits for patients with HRPC with an acceptable toxicity profile. We need to further evaluate who might benefit most from this regimen.
Prostate cancer is the most common malignancy of elderly men in the United States. Since there is no curative treatment for advanced prostate cancer, exploration of novel modalities of treatment is ...essential. Telomerase, a ribonucleoprotein, is detected in the vast majority of prostate cancer, but not in normal or benign prostatic hyperplasia tissues. Thus, telomerase is expected to be a very strong candidate for targeted therapy of prostate cancer. In this study, we synthesized a 19-mer antisense oligonucleotide against the RNA component of human telomerase (hTR) linked to a 2-5A molecule (2-5A-anti-hTR) and examined its cytotoxic effect on prostate cancer cells. The 2-5A antisense strategy relies on the recruitment and activation of RNase L at the site of targeted RNA sequence. We here show that treatment with 2-5A-anti-hTR in the presence of a cationic liposome reduced cell viability of tumor cell lines tested to 9-18% within 6 days. In contrast, normal fibroblast cells were resistant to the treatment. Its effect was mainly due to induction of apoptosis by activated caspase family members. Furthermore, treatment of subcutaneous tumors in nude mice with 2-5A-anti-hTR significantly suppressed the tumor growth through induction of apoptosis (P<0.001). The treatment with 2-5A-anti-hTR may be a promising strategy for the treatment modality of prostate cancer with telomerase activity.
Apoptosis is a genetically encoded cell death process and is a pathway that may be disrupted in tumor cells. Therefore, therapies that restore the ability to undergo apoptosis are promising for the ...treatment of tumor cells. We have demonstrated that the transfer of apoptosis-inducible genes inhibits the growth of tumors in vitro and in vivo through induction of apoptosis. However, to restrict induction of apoptosis to tumor cells, we need to explore a tumor-specific expression system of these genes. In the present study, we developed the telomerase-specific transfer system of apoptosis-inducible genes, utilizing the promoter of the human telomerase catalytic subunit (hTERT) gene. Approximately 90% of tumors have telomerase activity whereas most normal cells do not express the activity. These observations indicate that telomerase is a particularly attractive target for the tumor-specific expression system of vectors. We demonstrate here that by using the hTERT promoter-driven caspase-8 expression vector (hTERT/caspase-8), apoptosis is restricted to telomerase-positive tumor cells of wide range, and is not seen in normal fibroblast cells without telomerase activity. Furthermore, treatment of subcutaneous tumors in nude mice with the hTERT/caspase-8 construct inhibited tumor growth significantly because of induction of apoptosis (p < 0.01). The telomerase-specific expression of apoptosis-inducible genes afforded by the hTERT promoter, therefore, may be a novel and promising targeting approach for the treatment of tumors with telomerase activity.
Conditioned media (CM) derived from mesenchymal stem cells (MSC) is known to induce hair regrowth in androgenic alopecia.
The objectives of the study were to assess the efficacy and safety of one ...type of MSC-CM, the CM derived from dental pulp stem cells obtained from human exfoliated deciduous teeth (SHED-CM) and to compare the efficacy of SHED-CM with and without dihydrotestosterone synthesis inhibitor (DHT-inhibitor).
Eighty-eight male androgenic alopecia subjects with Hamilton-Norwood Classification (H-N C) I-VII were evaluated by trichoscopy to explore which trichoscopic factors statistically correlated with H-N C. After being screened, 33 subjects received six SHED-CM treatments at 1-month intervals. Clinical severity was assessed through global and trichoscopic images from baseline to 9th month.
SHED-CM was effective for 75% of subjects regardless of disease severity, concomitant DHT-inhibitor use, and age. Adverse effects including pain and small hemorrhages were transient and mild. We also found that clinical hair status evaluated by absolute values of three quantitative trichoscopic factors (maximum hair diameter, vellus hair rate, and multi-hair follicular unit rate) showed a good correlation with H-N C stages, and what is more-a scoring system of these three factors can be a possible predictor of SHED-CM efficacy.
We have shown that SHED-CM provides global and trichoscopic image improvement for androgenic alopecia, regardless of concomitant DHT-inhibitor use.
Radium-223 dichloride (Ra-223) is an alpha-emitting radioisotope that targets osteoblastic metastasis of prostate cancer. For Ra-223, a favorable safety profile has been described. However, here we ...report a case of a fatal hematologic toxicity following the administration of Ra-223 observed at our hospital. An 80-year-old man with castration-resistant prostate cancer (CRPC) and multiple metastatic bone lesions was treated with Ra-223. He was complicated with systemic edema, constipation, and decline of renal function. One week later, he developed pancytopenia which deteriorated gradually, and died with severe prolonged pancytopenia and pneumonia 4 weeks after administration of Ra-223. Our report demonstrates the risk of fatal hematologic toxicity of Ra-223 even though pretreatment clinical and laboratory findings fulfill the selection criteria. Caution should be paid when prescribing Ra-223 to a patient with systemic edema, constipation, and decline of renal function.
Objectives
This study aimed to evaluate the risk of bladder cancer after intensity‐modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk ...post‐radical prostatectomy (RP) using propensity score‐matched analysis and to assess the risk factors for bladder cancer.
Methods
This retrospective study included 2067 patients with non‐metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow‐up time as matched covariates. A propensity score‐matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared.
Results
In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score‐matched analysis, the 5‐year bladder cancer‐free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436–18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000–1.001, p = 0.010, respectively).
Conclusions
IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.
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