Medical therapy for clinical benign prostatic hyperplasia:α1 Antagonists,5α reductase inhibitors and their combination

Medical therapy for clinical benign prostatic hyperplasia(BPH)has advanced significantly in the last 2 decades.Many new a1 antagonists and 5a reductase inhibitors(5ARi)are now commercially available.The practicing urologist must decide on the most appropriate medication for his patients,taking into consideration various factors like efficacy,dosing regime,adverse effects,cost,patient’s socioeconomic background,expectations,drug availability and his own clinical experience.The use of combination therapy added further to the complexity in clinical judgment when prescribing.We highlight some of the key points in prescribing a1 antagonists,5ARi and their combination,based on our viewpoints and experience as urologists in an Asian clinical setting.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

Background: Photodynamic therapy (PDT) is a less invasive cancer treatment using photochemical reactions induced by light irradiation to a photosensitizer (PS). Highly selective PDT with fast accumulation of the PS in target site might be a promising treatment option for drug-resistant prostate cancer facing high incidence rate of elderly men who have no effective treatment options and require a minimally invasive treatment. Hemagglutinating virus of Japan envelope (HVJ-E) allows selective and fast drug delivery to the drug-resistant prostate cancer cells via rapid cell membrane fusion. PS named porphyrus envelope (PE) has been developed by insertion of lipidated protoporphyrin IX (PpIX lipid) into HVJ-E. In this study, we investigated the optimal conditions for PE preparation and laser irradiation for highly selective PDT using PE with a short drug-light interval. Materials and Methods: Human hormon refractory prostate cancer cell line PC-3 and human normal prostate epithelial cell line PNT2 were cultured. PpIX lipid uptake and cytotoxicity of PDT in the cells incubated with PE for 10 min were evaluated by measuring fluorescence intensity and by using a cell counting reagent 24 h after PDT, respectively. Results: PpIX lipid uptake and cytotoxicity of PDT were increased with PpIX lipid concentration. Cytotoxicity of PDT using PE was more than 9 times as strong as that with PpIX lipid and PpIX induced by 5-aminolevulinic acid. Much stronger cytotoxicity was induced in PC-3 cells than PNT2 cells with the ratio of cell death rate for cancer to normal cells up to 4.64 ± 0.09. Conclusions: Fast PS delivery with HVJ-E allows highly selective PDT with a short drug-light interval. Therefore, PDT using PE has a potential to shorten treatment period and reduce side effects of PDT.

Radioiodine therapy for castration-resistant prostate cancer following prostate-specific membrane antigen promoter-mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Outcomes of T3a Prostate Cancer with Unfavorable Prognostic Factors Treated with Brachytherapy Combined with External Radiotherapy and Hormone Therapy

Objective To evaluate the outcomes of T3 a prostate cancer with unfavorable prognostic factors treated with permanent interstitial brachytherapy combined with external radiotherapy and hormone therapy.Methods From January 2003 to December 2008,38 patients classified as T3 a prostate cancer with unfavorable prognostic factors were treated with trimodality therapy(brachytherapy + external radiotherapy + hormone therapy).The prescription dose of brachytherapy and external radiotherapy were 110 Gy and 45 Gy,respectively.The duration of hormone therapy was 2-3 years.The endpoints of this study included biochemical failure-free survival(BFFS),distant metastasis-free survival(DMFS),cancer-specific survival(CSS),and overall survival(OS).Survival curves were calculated using the Kaplan-Meier method.The Log-rank test was used to identify the prognostic predictors for univariate analysis.Results The median follow-up was 71 months.The serum pre-treatment prostate-specific antigen(PSA) level ranged from 10.0 to 99.8 ng/ml(mean 56.3 ng/ml),the Gleason score ranged from 5 to 9(median 8),and the percentage of positive biopsy cores ranged from 10% to 100%(mean 65%).The 5-year BFFS,DMFS,CSS,and OS rates were 44%,69%,82%,and 76%,respectively.All biochemical failures occurred within 40 months.The percentage of positive biopsy cores was significantly correlated with BFFS,DMFS,and OS(all P=0.000),and the Gleason score with DMFS(P=0.000) and OS(P=0.001).Conclusions T3 a prostate cancer with unfavorable prognostic factors presents not so optimistic outcome.Hormone therapy should be applied to prolong the biochemical progression-free or metastasis-free survival.The percentage of positive biopsy cores and the Gleason score are significant prognostic factors.

Adjuvant radiotherapy for pathologically advanced prostate cancer improves biochemical recurrence free survival compared to salvage radiotherapy

AIM: To evaluate the long-term outcomes of patients receiving adjuvant and salvage radiotherapy following prostatectomy with adverse pathologic features and an undetectable prostate specific antigen(PSA).METHODS: A retrospective review was performed of patients who received post-prostatectomy radiation at Loyola University Medical Center between 1992 and 2013. Adverse pathologic features(Gleason score ≥ 8, seminal vesicle invasion, extracapsular extension, pathologic T4 disease, and/or positive surgical margins) and an undetectable PSA following prostatectomy were required for inclusion. Adjuvant patients received therapy with an undetectable PSA, salvage patients following biochemical recurrence(BCR). Post-radiation BCR, overall survival, bone metastases, and initiation of hormonal therapy were assessed. Kaplan-Meier time-to-event analyses and stepwise Cox proportional hazards regression(HR) were performed. RESULTS: Post-prostatectomy patients(n = 134) received either adjuvant(n = 47) or salvage(n = 87) radiation. Median age at radiotherapy(RT) was 63 years, and median follow-up was 53 mo. Five-year post-radiation BCR-free survival was 78% for adjuvant vs 50% salvage radiotherapy(SRT)(Logrank P = 0.001). Patients with radiation administered following a detectable PSA had an increased risk of BCR compared to undetectable: PSA > 0.0-0.2: HR = 4.1(95%CI: 1.5-11.2; P = 0.005); PSA > 0.2-1.0: HR = 4.4(95%CI: 1.6-11.9; P = 0.003); and PSA > 1.0: HR = 52(95%CI: 12.9-210; P < 0.001). There was no demonstrable difference in rates of overall survival, bone metastases or utilization of hormonal therapy between adjuvant and SRT patients. CONCLUSION: Adjuvant RT improves BCR-free survival compared to SRT in patients with adverse pathologic features and an undetectable post-prostatectomy PSA.

Immunotherapy for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative treatment.Even for patients who can undergo resection for curative treatment of HCC,up to 50%recur.For patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local treatments.Such patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed inappropriate.There are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor inhibitors.This minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial diagnosis.We also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

垂体催乳素瘤的临床特点及诊治要点更新--基于《2022版ICCE/AME垂体催乳素瘤临床实践共识》解读

垂体催乳素瘤是一种由垂体催乳素细胞瘤过量合成和分泌催乳素引起的神经内分泌疾病,垂体催乳素瘤的规范化诊疗对于恢复并维持患者的正常垂体功能并提高其生活质量具有重要意义。2022年1月,《欧洲内分泌杂志》发布了国际临床内分泌学分会(ICCE)与意大利临床内分泌学家协会(AME)关于垂体催乳素瘤的临床实践最新共识申明——《2022版ICCE/AME垂体催乳素瘤临床实践共识》(简称2022版ICCE/AME新共识)。2022版ICCE/AME新共识立足最新循证医学证据,对于垂体催乳素瘤的临床诊治问题进行系统性阐述、分析和建议。本文围绕2022版ICCE/AME新共识关于垂体催乳素瘤的诊断、治疗、特殊人群、多巴胺激动剂抵抗及侵袭性疾病等诊治要点更新进行解读,希望有助于全科医生及内分泌专科医生对于垂体催乳素瘤的认识,为其临床实践的规范化诊疗提供参考。

肝癌靶向联合免疫治疗耐药后的二线治疗方案研究进展

近年来,靶向和免疫单药及联合治疗晚期肝癌的临床研究为一线用药方案选择提供了丰富的疗效与安全性证据。然而,对于肝癌二线治疗方案的选择,目前各项临床指南尚无统一意见,原因在于现有循证医学证据局限于索拉非尼失败后的选择,而对于新的一线方案,如靶向免疫联合治疗肝癌耐药后的二线治疗方案,依然缺乏高证据等级的临床试验结论。本文回顾了目前临床试验研究结果,根据药物作用的不同机制,对靶向免疫一线治疗耐药后肝癌二线治疗方案的研究进行了归纳,并系统总结近年研究进展。对于一线靶免联合治疗耐药的肝癌患者,靶向联合治疗、免疫双抗治疗均有望提高疗效、改善生存,未来还需更多前瞻性临床研究数据,为靶免联合治疗耐药的肝癌患者提供有效、安全的治疗方案。

Comprehensive treatment for metastatic castration-resistant prostate cancer with neuroendocrine differentiation:a case report

Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.

免疫细胞及炎症因子对晚期肺癌一线化疗效果的预测价值

【目的】探讨T淋巴细胞亚群、肿瘤浸润T淋巴细胞(Tils)及炎症因子对晚期肺癌一线化疗效果的预测价值。【方法】检测98例首诊TNM分期为Ⅲ/Ⅳ期的非小细胞肺腺癌患者的血清白细胞介素1α(IL-1α)、IL-6、IL-17、γ-干扰素(INF-γ)水平及T淋巴细胞亚群CD4^(+)T、CD8^(+)T、调节性T细胞、CD57^(+)细胞、Granzyme B^(+)细胞、CD45RO^(+)细胞比例;所有患者均接受紫杉醇注射液+顺铂化疗,治疗4个周期后评定疗效,并据此分为有效组和无效组,分析化疗无效的影响因素及预测疗效的有效标志物。【结果】化疗后,98例患者中69例化疗有效,29例无效。无效组患者淋巴结转移占比及调节性T细胞、IL-1α表达水平均高于有效组(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例均低于有效组(P<0.05)。多因素逐步Logistic回归分析结果显示,调节性T细胞、IL-1α水平高是肺癌患者化疗无效的危险因素(P<0.05),CD57^(+)细胞、CD45RO^(+)细胞比例高是保护因素(P<0.05)。受试者工作特征(ROC)曲线分析显示,调节性T细胞、CD57^(+)细胞、CD45RO^(+)细胞、IL-1α水平预测化疗效果的灵敏度分别为82.76%、86.21%、89.66%、93.10%,四者联合的灵敏度、特异度和曲线下面积(AUC)分别为82.76%、97.10%、0.957。【结论】T淋巴细胞亚群、Tils及炎症因子水平与晚期肺癌治疗效果密切相关,其可作为预测疗效的敏感指标。

滋肾润肺方辅助化疗治疗中晚期肺癌气阴两虚证患者的临床疗效

【目的】探讨滋肾润肺方联合化疗治疗中晚期肺癌气阴两虚证患者的疗效。【方法】两院收治的80例中晚期肺癌气阴两虚证患者,随机分为化疗组与联合组,每组40例。化疗组采用常规肺癌化疗方案,联合组在此基础上同时给予滋肾润肺方口服。比较两组患者的疗效、疾病进展时间(TTP)、1年存活率、1年无进展生存(PFS)率,治疗前后中医症状积分、卡氏评分(KPS)改善情况,骨髓抑制发生情况。【结果】联合组治疗总有效率(RR)为37.5%(15/40)、疾病控制率(DCR)为82.5%(33/40),化疗组RR为27.5%(11/40)、DCR为70.0%(28/40),两组比较差异均无统计学意义(P>0.05)。化疗组TTP为6.5(4.2~8.4)个月,1年存活率为30.0%(12/40),1年PFS率为85.0%(34/40);联合组TTP为7.2(5.5~9.3)个月,1年存活率35.0%(14/40),1年PFS率为87.5%(35/40),两组比较差异均无统计学意义(P>0.05)。与治疗前比较,两组治疗后中医症状积分均明显降低,且观察组各项指标下降更显著(P<0.05)。治疗后,联合组KPS评分稳定率为90.00%(36/40),明显高于化疗组的70.00%(28/40)(P<0.05)。联合组骨髓抑制的总发生率为17.5%(7/40),低于化疗组的42.5%(17/40)(P<0.05)。【结论】滋肾润肺方联合化疗可有效改善患者的生活质量,且能降低骨髓抑制的发生率。

基于妇科肿瘤耐药治疗中工程化外泌体的应用研究进展

妇科恶性肿瘤严重威胁着女性健康,在女性各类疾病中其发病率和死亡率均位居前列,关键原因在于传统化疗对复发、耐药患者的疗效欠佳。近年来,探讨肿瘤细胞化疗的耐药机制,开发新型药物逆转耐药已成为妇科肿瘤研究者关注的热点。外泌体(exosome)是一种来源于细胞内溶酶体微粒内陷的多囊泡体,具有低免疫原性、先天靶向性及获得靶向性和高传递效率等生物学特性。因此,外泌体可作为一种理想的、天然的纳米递送药物载体,不仅可以降低肿瘤细胞对化疗药物的耐药性,提高药物治疗效果,还可以减少化疗药物对全身的毒副反应。本文就外泌体作为妇科肿瘤耐药治疗中药物载体的研究进展进行综述,以期对妇科肿瘤的临床治疗提供帮助。

揿针联合穴位贴敷治疗对胃肠道肿瘤化疗患者胃肠道反应及睡眠质量的影响

目的 探讨胃肠道肿瘤化疗患者应用揿针联合穴位贴敷治疗对胃肠道反应及睡眠质量的影响效果。方法 选择河南省肿瘤医院中西结合科住院的胃肠道肿瘤化疗患者96例(2021年10月至2023年6月入组)患者研究,参照计算机数字表法分为2组,每组48例,包括对照组(穴位贴敷治疗)与试验组(揿针联合穴位贴敷治疗)。比较干预前后2组患者胃肠道反应及睡眠质量的变化。结果 治疗前,2组恶心程度评分、呕吐程度评分、食欲情况评分差异无统计学意义(P>0.05),治疗5 d、治疗7 d 2组均有改善,且试验组恶心程度评分、呕吐程度评分、食欲情况评分更低,差异有统计学意义(P<0.05);治疗7 d,试验组恶心频率与呕吐频率均低于对照组(P<0.05);治疗前,2组睡眠质量差异无统计学意义(P>0.05),治疗7 d试验组睡眠质量PSQI评分低于对照组(P<0.05);试验组总并发症发生率比对照组低(P<0.05)。结论 胃肠道肿瘤化疗患者应用揿针联合穴位贴敷治疗可以更好地减轻化疗所致的胃肠道反应,改善食欲及睡眠质量,值得应用。

长链非编码RNA在肝细胞癌耐药中的研究进展

肝细胞癌是原发性肝癌中最常见的类型,进展迅速、侵袭力强,治疗方法多样。但因其发生、发展所涉及的基因较多、机制复杂,不可避免地出现了治疗耐药性,导致治疗效果不明显,而耐药相关机制尚未完全明确。lncRNA是一类具有多种生物学功能的新型非编码RNA,能通过基因突变等作用于肝癌的发展、转化和侵袭,同时可以通过影响肿瘤免疫微环境、调节肿瘤细胞生物学功能等参与肝癌耐药。本文对lncRNA在肝细胞癌放化疗、靶向和免疫治疗耐药中的作用机制及相关进展进行综述,以期为解决肝癌耐药提供新思路。

前列腺癌骨转移治疗研究进展

前列腺癌的发生率不断增加,骨骼是其远处转移常见部位。发生骨转移的患者,治疗效果不佳。目前,针对前列腺癌发生骨转移的患者,其治疗方法多样化,多种治疗措施的应用能改善患者生活质量,延长患者生存时间。本文总结了前列腺癌骨转移的镇痛药物治疗、骨改良药物治疗、放射性核素治疗以及手术治疗等,望为临床工作者带来不同的治疗思路。

PARP抑制剂在上皮性卵巢癌中的耐药机制及解决策略

上皮性卵巢癌(epithelial ovarian cancer,EOC)的致死率在女性生殖系统恶性肿瘤中居首位。EOC的传统治疗方案是肿瘤细胞减灭术联合铂类药物为基础的化疗,但2年内仍有约70%的患者复发或耐药。多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂通过对乳腺癌相关基因(breast cancer-related gene,BRCA)突变的肿瘤细胞发挥合成致死效应,为EOC提供了全新的治疗模式。PARP抑制剂为EOC靶向维持治疗带来重大突破,然而仍有患者在治疗中逐步耐药,主要的耐药机制包括同源重组修复途径恢复、药物靶点变化和致死性DNA损伤减少,目前的解决策略包括PARP抑制剂联合DNA损伤修复抑制剂、联合抑制同源重组修复通路的药物、联合传统抗癌方案、联合P-糖蛋白(P-glucoprotein,P-gp)抑制剂以及更换其他类型的PARP抑制剂。

多发性骨髓瘤耐药机制和分子靶向治疗新进展——第20届国际骨髓瘤学会年会研究热点报道

多发性骨髓瘤(MM)是一种血液恶性肿瘤,其特征为恶性浆细胞的克隆性增殖。蛋白酶体抑制剂、免疫调节药物以及自体造血干细胞移植治疗明显改善了MM患者的生活质量和生存状况,然而几乎所有患者都将产生耐药导致疾病复发难治,预后较差。因此,探究MM患者耐药性产生的分子机制,寻找新的治疗靶点并开发新的靶向治疗策略尤为重要。现对MM耐药机制和分子靶向治疗研究的最新进展进行综述。

Hippo及Notch信号通路在眼睑基底细胞癌中的研究进展

眼睑基底细胞癌(BCC)是眼睑恶性肿瘤中最常见的类型。手术切除是治疗眼睑BCC的公认金标准,但对于局部晚期或转移性BCC,较大的手术风险和不良预后是困扰医患的最大问题,因此有必要探索新治疗方案。目前靶向治疗具有良好前景,但现有的靶向药物(Hedgehog信号通路抑制剂)面临难以完全清除肿瘤、毒性作用严重以及耐药的发生问题。鉴于以上情况,开发新的靶向药物对治疗该病具有重要意义。Hippo信号通路和Notch信号通路在眼睑BCC的发生和发展中起着重要作用,可能成为治疗的新靶点。因此,本文综述了Hippo信号通路和Notch信号通路在眼睑BCC中的研究进展,旨在为眼睑BCC的靶向治疗提供新的思路。

抗体药物偶联物在人表皮生长因子受体2低表达胃癌中的应用研究进展

胃癌(GC)是极具异质性和侵袭性的消化系统恶性肿瘤之一,传统化疗药物及曲妥珠单抗等人表皮生长因子受体2(HER2)靶向药物在GC的治疗过程中仍然存在耐药性发生率高、毒副作用大、患者耐受差等缺点。因此,研发更为有效的抗GC药物势在必行。目前针对HER2的新型靶向药层出不穷,但在某些情况下无效或产生耐药,这与HER2在某些GC细胞中低表达有关,HER2低表达(HER2 IHC1+或IHC2+/ISH-)约占全部类型的40%~60%,但在临床实践中,这类患者仍被报告为HER2阴性GC。因此准确检测HER2表达状态对于确定可能受益于曲妥珠单抗治疗的患者至关重要。抗体药物偶联物(ADC)的出现为HER2阳性GC提供了新的治疗选择,凭借其精准高效的抗肿瘤作用,有望在未来替代传统GC化学疗法。近期有研究发现ADC可能在HER2低表达GC中具有潜在抗肿瘤活性,相关临床研究正在评估其在HER2低表达GC治疗中的有效性和安全性。本文就靶向治疗时代ADC在HER2低表达GC患者中的应用和最新研究进展作一综述,并讨论HER2靶向ADC在应用和研发过程中面临的挑战。