Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate gland:A case report

BACKGROUND Adenocarcinoma is the most common subtype of prostate cancer.Prostatic urothelial carcinoma(UC)typically originates from the prostatic urethra.The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon.CASE SUMMARY We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland.The patient underwent a transrectal ultrasound-guided biopsy,and the pathology test revealed UC.Subsequently,transurethral laser prostatectomy was performed,and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3+4 and highgrade UC.Therefore,the patient was treated with androgen deprivation therapy,systemic chemotherapy,and immunotherapy.Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0,stage IVA.Therefore,the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection.The final pathology test of the prostate gland revealed acinar-type adenocarcinoma,Gleason pattern 4+3,pT2N0M0,and high-grade UC.The patient regularly presented to the clinic for postoperative follow-up evaluations.He did not experience any urinary discomfort.CONCLUSION According to our literature review,this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland.

Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer:Identification,prognosis and survival,genetic and epigenetic factors

Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.

The Inhibitory Effects of an Antisense u-PAR Vector on Invasion of Highly Invasive Human Prostate Carcinoma PC-3M Cell Subclones

To observe the inhibitory effects of an antisense u-PAR vector on invasion of highly invasive PC-3M cell subclones, the effects of the antisense u-PAR on activity of MMP-9 in those highly invasive cell subclones were detected by a quantitative RT-PCR and zymography. The monolayer invasion assay and colony formation assay in soft agar were used. And tumorigenesis rate and invasions by the cell subclones with or without the antisense u-PAR were observed in nude mice. It was found that in vitro growth of highly invasive PC-3M cell subclones transfected with the antisense u-PAR was declined, and the ability of anchorage-independent growth of those cell subclones was found decreased sharply, with the inhibiting rate becoming 79%and 60% , respectively. Although the anti-sense u-PAR didn't change MMP-9 gene transcription, they could inhibit the activation of MMP-9 of highly invasive PC-3M cell subclones. Moreover, the tumorigenesis rate of the cell subclones with the antisense u-PAR decreased and the growth of a neoplasm also slowed down. The t tests showed the difference between experimental and control groups was statistically significant (P<0.01). The anti-sense u-PAR vector could not only inhibit the invasion ability of highly invasive PC-3M cell subclones in vitro but also restrain the growth of those cell subclones in vivo.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe3+,Cu2+reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

爱必妥对前列腺癌PC-3细胞功能学的影响

目的观察不同浓度爱必妥对前列腺癌PC-3细胞的增殖、侵袭及凋亡的作用,并初步探索其可能的作用机制。方法使用不同浓度的(10、20、40、80μg/mL)爱必妥作用于PC-3细胞24 h后,CCK-8检测细胞增殖活力变化;流式检测细胞凋亡变化;transwell检测细胞侵袭能力变化;RT-PCR检测EGFR mRNA表达变化;Western Blot法检测Bax和Bcl-2蛋白表达变化。结果CCK-8结果显示,不同浓度的爱必妥作用24 h后均可以抑制PC-3的细胞增殖活力(P<0.001),且药物抑制作用与浓度呈剂量依赖关系;凋亡检测结果显示,不同浓度的爱必妥均抑制PC-3细胞的侵袭能力(P<0.001),且药物抑制作用与浓度呈剂量依赖关系;凋亡检测结果显示,不同浓度的爱必妥均导致PC-3细胞的总凋亡比例增加(P<0.01),且这种促凋亡能力与与浓度呈剂量依赖关系;Western Blot结果显示,不同浓度的爱必妥均可以抑制Bc1-2蛋白表达(P<0.05),同时促进Bax蛋白表达(P<0.05),且抑制和促进作用与药物浓度呈剂量依赖关系;RT-PCR结果显示,不同浓度的爱必妥均可以抑制EGFR mRNA表达(P<0.05),且抑制作用与药物浓度同样呈剂量依赖关系。结论爱必妥可以抑制前列腺癌细胞PC-3的增殖和侵袭,促进细胞凋亡,且这种作用可能是通过抑制EGFR信号通路导致细胞凋亡而实现。

Secondary rectal linitis plastica caused by prostatic adenocarcinoma-magnetic resonance imaging findings and dissemination pathways:A case report

BACKGROUND Secondary rectal linitis plastica(RLP)from prostatic adenocarcinoma is a rare and poorly understood form of metastatic spread,characterized by a desmoplastic response and concentric rectal wall infiltration with mucosal preservation.This complicates endoscopic diagnosis and can mimic gastrointestinal malignancies.This case series underscores the critical role of magnetic resonance imaging(MRI)in identifying the distinct imaging features of RLP and highlights the importance of considering this condition in the differential diagnosis of patients with a history of prostate cancer.CASE SUMMARY Three patients with secondary RLP due to prostatic adenocarcinoma presented with varied clinical features.The first patient,a 76-year-old man with advanced prostate cancer,had rectal pain and incontinence.MRI showed diffuse prostatic invasion and significant rectal wall thickening with a characteristic"target sign"pattern.The second,a 57-year-old asymptomatic man with elevated prostatespecific antigen levels and a history of prostate cancer exhibited rectoprostatic angle involvement and rectal wall thickening on MRI,with positron emission tomography/computed tomography PSMA confirming the prostatic origin of the metastatic spread.The third patient,an 80-year-old post-radical prostatectomy,presented with refractory constipation.MRI revealed a neoplastic mass infiltrating the rectal wall.In all cases,MRI consistently showed stratified thickening,concentric signal changes,restricted diffusion,and contrast enhancement,which were essential for diagnosing secondary RLP.Biopsies confirmed the prostatic origin of the neoplastic involvement in the rectum.CONCLUSION Recognizing MRI findings of secondary RLP is essential for accurate diagnosis and management in prostate cancer patients.

Intraductal Prostatic Carcinoma: Epidemiological and Anatomopathological Aspects in Dakar

Introduction: Intraductal carcinoma is often associated with high-grade, high-stage adenocarcinoma. Its frequency is variable and it is considered a poor prognostic factor. In our context, when prostatic carcinoma is diagnosed, pathologists do not always report the presence of this anatomopathological entity. We therefore conducted a study to determine the epidemiological and anatomopathological profile of patients with this lesion in Dakar. Materials and Methods: This is a retrospective descriptive study covering a 1-year period from January to December 2022. It focused on cases of intraductal carcinoma diagnosed among prostatic carcinomas collected in the anatomopathology laboratories of Hôpital Général Idrissa Pouye (HOGIP) and Hôpital Militaire de Ouakam (HMO). It was based on archives of anatomopathological reports, blocks and slides. A total of 200 cases of prostatic carcinoma were collated and reviewed to identify those presenting with intraductal carcinoma according to the diagnostic criteria of Guo and Epstein. Results: 87 cases of intraductal carcinoma were found, representing 43.5% of prostatic carcinomas. The mean age was 71 years. Patients in their seventh decade were the most represented, i.e. 42.5%. The majority of samples examined were biopsies (72.4%). The mean PSA level was 965.91 ng/ml, with extremes ranging from 0.03 to 10,000 ng/ml. Histologically, 96.5% of cases (N = 84) were invasive prostatic carcinoma. Gleason score 8 (4 + 4) was the most common, accounting for 42.53% (N = 37). On average, the study found four (04) foci of intraductal carcinoma per specimen, with extremes ranging from 1 to 30. Dense cribriform architecture accounted for 78.16%, loose cribriform for 11.5%, solid for 8.04% and micropapillary for 2.3%. Six cases (6.9%) showed foci of comedonecrosis. The vast majority of radical prostatectomies (87.5%) were classified as pT3. Node invasion and perineural sheathing were observed in 12.5% and 52.32% of cases respectively. Conclusion: Intraductal carcinoma is a poor prognostic factor that must be systematically reported in the anatomopathological report. In Senegal, it is often associated with advanced stage, high-grade carcinoma and high PSA levels.

Preliminary Study of Selenium (Se) Toxicity in Human Prostate Carcinoma (PC3) Cells with the Overexpression of Selenocysteine Synthase (SecS) Gene

Selenium (Se) is a trace element required for normal body function. Its supplementation of human diet at standard optimum amount prevents oxidative damages in cells and could be a viable method in the prevention of diseases related to DNA damage, including cancer, neurodegenerative diseases and aging. While Se anticancer properties have been linked to its ability to remove excess Reactive Oxygen Species (ROS) in cells, the underlying molecular mechanism remains unknown. Recent studies have shown that the removal of ROS alone cannot account for Se anticancer properties. To really comprehend the molecular basis of Se anticancer properties, current researches now focus on the metabolism of Se in the cell, especially Se-containing amino acids. Selenocysteine (Sec) is a novel amino acid and one of the selenium-containing compounds in the cell. It is essential in the maintenance of the integrity of its parent proteins, some of which include enzymes such as Glutathione Peroxidases (GPXs) and Thioredoxin Reductases (TrXs). We propose in this study that the overproduction of Sec via the overexpression of Selenocysteine synthase (SecS) gene and Se supplementation induced cell death in Prostate Carcinoma (PC-3) cells. Although the mechanism underlying the cell death induction is unknown, we propose it could be due to the random incorporation of Sec into proteins at high concentration, causing premature protein degradation and cell death. The outcome of this study showed that increasing the concentration of intracellular Se-containing amino acids may provide important clinical implications for the treatment of cancer.

Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.

Manganese antagonizes iron blocking mitochondrial aconitase expression in human prostate carcinoma cells

Aim： To investigate the possible role of manganese in the regulation of mitochondrial aconitase （mACON） activity human prostate carcinoma cell line PC-3 cells. Methods： The mACON enzymatic activities of human prostate carcinoma cell line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide-coupled assay. Immunoblot and transient gene expression assays were used to study gene expression of the mACON. The putative response element for gene expression was identified using reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays. Results： In vitro study revealed that manganese chloride （MnCI2） treatment for 16 h inhibited the enzymatic activity of mACON, which induced the inhibition of citrate utility and cell proliferation of PC- 3 cells. Although results from transient gene expression assays showed that MnCI2 treatment upregulated gene translation by approximately 5-fold through the iron response element pathway, immunoblot and reporter assays showed that MnCl2 treatments inhibited protein and gene expression of mACON. This effect was reversed by cotreatment with ferric ammonium citrate. Additional reporter assays with site-directed mutagenesis and electrophoretic mobility-shift assays suggested that a putative metal response element in the promoter of the mACON gene was involved in the regulation of MnCh on the gene expression of mACON. Conclusion： These findings suggest that manganese acts as an antagonist of iron, disrupting the enzymatic activity and gene expression of mACON and citrate metabolism in the prostate.

Synchronous primary carcinomas of the bladder and prostate

Aim： To determine the incidence of adenocarcinoma of the prostate for patients undergoing radical cystoprostatectomy for bladder cancer in Taiwan. Methods： A total of 248 patients in Taiwan who were histologically confirmed for transitional cell carcinoma of the bladder underwent cystoprostatectomy. Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals was performed. Results： Of the 248 patients, 10 （4.03%） were found to have prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to be at stage T1 or T2, and two at T3 and T4, respectively. This rate of incidentally found prostate cancer amongst our bladder cancer patients appeared to be lower than that found in bladder cancer patients in similar studies in USA. Conclusion： Although the incidence of incidental prostate cancer in patients in Taiwan with bladder cancer is not high compared with that in Western countries, we suggest that digital rectal examination and prostate-specific antigen （PSA） are important screening tools for men with bladder cancer, especially for those aged 60 years and older in Taiwan.

Small-cell neuroendocrine carcinoma of the prostate： are heterotransplants a better experimental model？

Small-cell neuroendocrine carcinoma of the prostate （SCNCP） is an uncommon type of prostate cancer. However, it is of clinical importance because it is one of the most aggressive tumors of the prostate with a very poor prognosis. There exist few artificially cultured tumor cell lines to study SCNCE Then, another approach to that study consists in the use of fresh tumor tissue obtained from patients and its heterotransplantation into host mice. The purpose of this review is to integrate data from more than 20 years of heterotransplantation research in the study of small-cell neuroendocrine carcinoma of the prostate （SCNCP）. Heterotransplantation has provided data regarding the histopathology, karyotype, DNA content, cell cycle frequency, tumor markers, androgen receptor expression, metastasis and take rate of this prostate disease. When possible, comparisons between original in situ specimens removed from patients and heterotransplanted tissue from host mice have been made. There are advantages, as well as limitations, that have been identified for SCNCP heterotransplants versus xenotransplantation of cultured cells. Overall, heterotransplanted tumors are better than conventional tumor xenografts at retaining tumor morphology, pathology, secretory activity and expression of tumor markers of the patient＇s original specimen. Furthermore, heterotransplanted tissue preserves the three-dimensional tumor architecture of the prostate to maintain critical stromal-epithelial cell interactions.

Intraductal carcinoma of prostate(IDC-P): from obscure to significant

The concept of intraductal carcinoma of prostate （IDC-P） has evolved over the years and its clinieopathologic significance has come to be more clearly appreciated. In contrast to morphologically malignant intraductal lesions that represent earlier stages of the malignant process in other anatomic sites such as the breast, IDC-P has now been generally recognized as a prognostically unfavorable manifestation of later stage spreading of its invasive counterpart. We here briefly review the evolution of the IDC-P concept, the histological diagnostic criteria and differential diagnosis, the clinical significance, as well as recent molecular data of IDC-P.

Inhibitory effect of a new gossypol derivative apogossypolone (ApoG2) on xenograft of human prostate cancer cell line PC-3

Objective: To investigate the inhibitory effect of apogossypolone (ApoG2) on prostate cancer cell line PC-3 in vivo, and explore its mechanism. Methods: The models of transplantation tumors in Balb/c nu/nu mice were established via subcutaneous injection of PC-3 cells and the tumor-transplanted mice were divided into 4 groups: control group and three ApoG2 treatment groups, with 10 mice in each group. Volumes of the tumor were estimated every 2 d and the morphology of tumor tissues was observed. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and caspase-8 in tumor tissues. Results: ApoG2 (2.5 mg/kg-10 mg/kg) given intraperitoneally once a day can obviously inhibit the growth of subcutaneous prostatic carcinoma implant. The tumor volume decreased obviously when the treatment dosage was bigger than 5.0 mg/kg (P<0.01). Meanwhile, ApoG2 decreased the expression of PCNA and CD31, and enhanced the expression of caspases-3, caspase-8 in tumor tissues. Conclusion: ApoG2 exert an inhibitory effect on prostatic carcinoma possibly by inducing apoptosis and inhibiting tumor angiogenesis.

Contragestazol (DL111-IT) inhibits proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo

Aim： To evaluate the antiproliferative activity of contragestazol （DL111-IT） on the human prostate cancer cell line PC3 in vitro and in vivo and to elucidate its potential molecular mechanisms. Methods： The cell killing ability of DL111-IT was measured by the 3-（4,5-dimethylthia-zol,2-yl）-2,5-diphenyltetrazolium bromide （MTT） reagent assay method and the tumor xenograft model. The cell cycle was analyzed by flow cytometry and protein expression, including retinoblastoma （pRb）, cyclin-dependent kinase 4 （CDK4） and cyclin D 1, was detected by Western blotting. Results： DL111-IT exhibited high efficiency on cell growth inhibition of the human androgen-independent prostate cancer cell line PC3. The drug concentration that yielded 50 % cell inhibition （IC50 value） was 9.9 mg/mL. In the PC3 tumor xenograft study, DL111-IT （1.25 mg/kg-20.0 mg/kg） given once a day for 10 days significantly inhibited tumor growth, with the inhibition rate ranging from 21% to 50 %. Flow cytometric analysis indicated that DL111-IT could cause GI arrest in the PC3 cell line, but not apoptosis. DL111-IT enhanced pRb expression and down-regulated CDK4 and cyclin D 1 expression, suggesting that cell cycle regulation might contribute to the anticancer property of DL 111- IT. Conclusion： DL111-1T inhibits the proliferation of human androgen-independent prostate cancer cell line PC3 in vitro and in vivo by a cell cycle regulation pathway.

Detection of androgen receptor (AR) and AR-V7 in small cell prostate carcinoma: Diagnostic and therapeutic implications

Objective:Small cell prostate carcinoma(SCPC)is a rare and highly malignant subtype of prostate cancer.SCPC frequently lacks androgen receptor(AR)and prostate-specific antigen(PSA)expression,and often responds poorly to androgen deprivation therapy(ADT).AR splice variant-7(AR-V7)is a truncated AR protein implicated in resistance to AR-targeting therapies.AR-V7 expression in castration-resistant prostate cancers has been evaluated extensively,and blood-based detection of AR-V7 has been associated with lack of response to abiraterone and enzalutamide.However,whether AR-V7 is expressed in SCPC is not known.Methods:Using validated antibodies,we performed immunohistochemistry(IHC)assay for the full-length AR(AR-FL)and(AR-V7)on post-ADT surgical SCPC specimens.Results:Seventy-five percent(9/12)of the specimens showed positive staining for the AR-FL with various intensities.Thirty-three percent(4/12)of the specimens showed positive staining for AR-V7.Among the specimens with positive AR-V7 staining,two samples displayed very weak staining,one sample showed weak-to-moderate staining,and one sample showed strong staining.All positive specimens displayed a heterogeneous pattern of AR-FL/AR-V7 staining.All specimens positive for AR-V7 were also positive for AR-FL.Conclusion:The study findings support the existence of measurable AR-FL and AR-V7 proteins in SCPC specimens.The results also have implications in detection of AR-V7 in specimens obtained through systemic sampling approaches such as circulating tumor cells.A positive AR-V7 finding by blood-based tests is not impossible in patients with SCPC who often demonstrate low PSA values.

Rapid induction of PC3/BTG2 gene by hepatopoietin or partial hepatectomy and its mRNA expression in hepatocellular carcinoma

BACKGROUND: The anti-proliferative gene, PC3 (pheochromocytoma cell 3)/BTG2 (B-cell translocation gene 2), is one of the early growth response genes and belongs to the BTG/Tob protein family. This study aimed to assess the effects of recombinant human hepatopoietin (HPO) and partial hepatectomy on rapidly induced expression of immediate-early genes and to investigate the expression of PC3/BTG2 mRNA in hepatocellular carcinoma (HCC) at different stages of progression. METHODS: After a rat model of partial hepatectomy was established, we investigated gene expression within I hour after 2/3 partial hepatectomy by representational difference analysis and in a primary cultured hepatocyte system. The expression levels of PC3/BTG2 from liver tissues of the rat model were assessed by RT-PCR and Northern blotting. Meanwhile, the expression of BTG2 mRNA in a tissue microarray of HCC was determined by in situ hybridization. RESULTS: The PC3/BTG2 gene was rapidly induced after 2/3 partial hepatectomy and its expression peaked within 1-2 hours after operation. HPO rapidly induced the expression of the genes c-fos, LRF-1, and PC3 in primary cultured rat hepatocytes, which might be one of the molecular mechanisms by which HPO stimulates hepatocyte proliferation. Positive BTG2 mRNA expression was detected in 71.19% (42/59) of the HCC samples and in 75% (3/4) of the normal liver tissue samples obtained from the region around the HCC tissues. PC3/BTG2 mRNA was located mainly in the cytoplasm of HCC cells and its expression was related to the degree of differentiation. CONCLUSIONS: Recombinant human HPO and partial hepatectomy rapidly induce the expression of the PC3/BTG2 gene. PC3/BTG2 mRNA is highly expressed in HCC cells and its expression is related to the degree of cell differentiation. The abnormal expression of PC3/BTG2 is closely related to the genesis and development of HCC, so PC3/BTG2 may play an important role in these processes. (Hepatobilimy Pancreat Dis Int 2009; 8: 288-293)

Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T genepolymorphism with susceptibility to renal cell carcinoma/prostatecancer

In this study,we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α(HIF1α)1772C/T gene polymorphism(rs 11549465)and renal cell carcinoma(RCC)/prostate cancer risk.We searched for relevant studies(before March 1,2019)on Cochrane Library,Embase,and PubMed.Studies meeting the inclusion criteria were recruited into this meta-analysis.The outcome of dichotomous data was showed in the way of odds ratios(OR),and 95%confidence intervals(CI)were also counted.In this investigation,there was no association between HIF1α1772C/T gene polymorphism and susceptibility to RCC in Caucasians,Asians as well as overall populations.In addition,HIF1α1772C/T gene polymorphism was not found to be relevant to the survival in RCC.Interestingly,the T allele was relevant to prostate cancer risk in all populations,but not in Caucasians and Asians.However,the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian,Caucasian,and all populations.In conclusion,the T allele of the HIF1α1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

Small-cell carcinoma of the prostate with negative CD56,NSE,Syn,and CgA indicators:A case report

BACKGROUND Small-cell carcinoma of the prostate(SCCP)is a clinically rare malignant tumor,accounting for<1%of all prostate tumors.However,negativity for all SCCP neuroendocrine markers is rare.Herein,we report a case of SCCP with completely negative neuroendocrine markers and explore its clinicopathologic features,thus improving the understanding of its clinical diagnosis and management.CASE SUMMARY We report the case of a 48-year-old patient with SCCP negative for common sensitive neuroendocrine-staining indicators.Dysuria was the first symptom,and rectal examination revealed a hard prostate,palpable nodules,diffuse prostate enlargement,no pressure pain,no blood staining in the finger sleeve,1.33 ng/mL total prostate-specific antigen level,and a free-to-total prostate-specific antigen ratio of 0.21 ng/mL.Ultrasound suggested a prostate size of 5.3 cm×5.8 cm×5.6 cm,and magnetic resonance imaging suggested prostate cancer.The lower posterior bladder wall,rectal mesentery,and bilateral seminal vesicles were invaded,with multiple lymph node metastases in the pelvis.A whole-body bone scan suggested an abnormally active multiple bone metabolism and possible bone metastases.Head and lungs computed tomography revealed no significant nodal shadow.Following a pathological diagnosis of SCCP after a prostate puncture,with negative indicators of common sensitive neuroendocrine staining,chemotherapy was administered;the patient died 4-5 mo after SCCP diagnosis.CONCLUSION SCCP is a rare disease characterized by atypical clinical symptoms,limited treatment options,a short survival period,and a poor prognosis.

双氢青蒿素对前列腺癌PC-3细胞自噬的诱导作用及其机制

目的探讨双氢青蒿素(DHA)对前列腺癌PC-3细胞的自噬诱导作用及其机制。方法用0、12.5、25、50、100μmol/L DHA处理PC-3细胞,采用CCK-8法检测细胞活力,克隆形成实验检测细胞增殖能力。取PC-3细胞,设置对照组(不做处理)、DHA组(50μmol/L DHA处理48h)、自噬抑制剂3-MA组(5mmol/L 3-MA处理48h)、DHA+3-MA组(50μmol/L DHA+5mmol/L 3-MA处理48h),采用Western blotting和RT-qPCR检测自噬相关蛋白[微管相关蛋白轻链3B(LC3B)、酵母Atg6同源物(Beclin-1)]的表达情况,透射电镜观察自噬小体形成情况,使用自噬双标慢病毒mCherry-GFP-LC3B转染PC-3细胞检测自噬流变化,CCK-8法检测细胞活力,流式细胞术检测细胞凋亡率。设置对照组(不做处理)、DHA组(50μmol/L DHA处理48h)、ROS抑制剂NAC组(5mmol/L NAC处理48h)、DHA+NAC组(50μmol/L DHA+5mmol/L NAC处理48h),采用Western blotting检测ROS/AMPK/mTOR信号通路相关蛋白的表达。用50μmol/L DHA处理PC-3细胞48h后提取总蛋白,分成Input组(全蛋白裂解液)、IP组(加入Beclin-1抗体)、IgG组(加入同等质量的IgG),采用免疫共沉淀(Co-IP)实验检测Beclin-1与Vps34、Bcl-2及HMGB1蛋白的相互作用。结果CCK-8法检测结果显示,PC-3细胞存活率随着DHA浓度的升高而降低,且呈剂量和时间依赖性(P<0.05);DHA作用24、48、72h的半数抑制浓度(IC50)分别为97.12、57.10、29.35μmol/L,据此选择50μmol/L DHA作用48h进行后续实验。克隆形成实验结果显示,PC-3细胞克隆形成率随着DHA浓度的升高而明显降低(P<0.01)。Western blotting和RT-qPCR检测结果显示,与对照组比较,DHA组PC-3细胞中Beclin-1、LC3B mRNA和蛋白表达水平明显升高(P<0.01);与DHA组比较,DHA+3-MA组PC-3细胞中Beclin-1、LC3B mRNA和蛋白表达水平明显降低(P<0.01)。透射电镜观察可见DHA组PC-3细胞中出现明显的自噬小体,且自噬小体数较对照组明显增多(P<0.05)。mCherry-GFP-LC3B慢病毒转染实验结果显示,与对照组比较,DHA组每细胞红黄斑点比增高(P<0.01),DHA+3-MA组每细胞红黄斑点比降低(P<0.01)。与DHA组比较,DHA+3-MA组细胞存活率降低,凋亡率增高(P<0.01)。与对照组比较,DHA组PC-3细胞中p-mTOR蛋白相对表达水平降低(P<0.05),p-AMPK蛋白相对表达水平升高(P<0.01);与DHA组比较,DHA+NAC组p-mTOR蛋白相对表达水平升高(P<0.01),p-AMPK蛋白相对表达水平降低(P<0.01)。Co-IP实验结果显示,DHA处理后Beclin-1与Bcl-2的作用减弱,与Vps34、HMGB1的结合增强。结论DHA可诱导前列腺癌PC-3细胞发生自噬,其机制可能与调控自噬相关基因Beclin-1、LC3及ROS/AMPK/mTOR信号通路有关。