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BMC Urology Oct 2022Prostate cancer (PCa) is one of the most diagnosed cancers in the world. PCa inevitably progresses to castration-resistant prostate cancer (CRPC) after androgen...
BACKGROUND
Prostate cancer (PCa) is one of the most diagnosed cancers in the world. PCa inevitably progresses to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment, and castration-resistant state means a shorter survival time than other causes. Here we aimed to define castration-dependent and -independent diver genes and molecular pathways in CRPC which are responsible for such lethal metastatic events.
METHODS
By employing digital gene expression (DGE) profiling, the alterations of the epididymal gene expression profile in the mature and bilateral castrated rat were explored. Then we detect and characterize the castration-dependent and -independent genes and pathways with two data set of CPRC-associated gene expression profiles publicly available on the NCBI.
RESULTS
We identified 1,632 up-regulated and 816 down-regulated genes in rat's epididymis after bilateral castration. Differential expression analysis of CRPC samples compared with the primary PCa samples was also done. In contrast to castration, we identified 97 up-regulated genes and 128 down-regulated genes that changed in both GEO dataset and DGE profile, and 120 up-regulated genes and 136 down-regulated genes changed only in CRPC, considered as CRPC-specific genes independent of castration. CRPC-specific DEGs were mainly enriched in cell proliferation, while CRPC-castration genes were associated with prostate gland development. NUSAP1 and NCAPG were identified as key genes, which might be promising biomarkers of the diagnosis and prognosis of CRPC.
CONCLUSION
Our study will provide insights into gene regulation of CRPC dependent or independent of castration and will improve understandings of CRPC development and progression.
Topics: Humans; Male; Rats; Animals; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Androgens; Gene Expression Regulation, Neoplastic; Orchiectomy; Cell Line, Tumor; Receptors, Androgen
PubMed: 36258196
DOI: 10.1186/s12894-022-01113-5 -
Tumour Biology : the Journal of the... 2024Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells... (Review)
Review
BACKGROUND
Tumor markers (TMs) are a heterogeneous group of molecules used in the diagnosis, prognosis and follow-up of cancer patients. During neoplastic differentiation, cells can either directly synthesize or induce the synthesis of TMs, and the release of these molecules into the bloodstream allows their quantification in biological fluids. Although very small concentrations of TMs are usually present in the serum or plasma of healthy subjects, increased concentrations may also be found in the presence of benign diseases or due to technical interference, producing false positive results.
MATERIAL AND METHODS AND RESULTS
Our review analyses the causes of false positives described between January 1970 to February 2023 for the TMs most frequently used in clinical practice: α-fetoprotein (AFP), β2-microglobulin (β2-M), cancer antigen 15-3 (CA 15-3), cancer antigen CA 19-9 (CA 19-9), cancer antigen CA 72-4 (CA 72-4), cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), chromogranin A (CgA), choriogonadotropin (hCG), cytokeratin 19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), human epididymis protein 4 (HE4), serum HER2 (sHER2), squamous cell carcinoma antigen (SCCA), protein induced by vitamin K absence-II (PIVKA-II), Pro-gastrin-releasing peptide (Pro-GRP), prostate-specific antigen (PSA), Protein S-100 (S-100) and thyroglobulin (Tg). A total of 247 references were included.
CONCLUSIONS
A better understanding of pathophysiological processes and other conditions that affect the concentration of TMs might improve the interpretation of results and their clinical application.
Topics: Male; Humans; Biomarkers, Tumor; Lung Neoplasms; Antigens, Neoplasm; Keratin-19; Carcinoembryonic Antigen; Prostate-Specific Antigen; Phosphopyruvate Hydratase; CA-125 Antigen
PubMed: 38517826
DOI: 10.3233/TUB-220023 -
The Israel Medical Association Journal... Oct 2018Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often...
BACKGROUND
Almost 50% of patients with germ-cell tumors (GCT) are subfertile, and every step of the treatment may further impair fertility. As a result, sperm banking is often advised prior to radical orchiectomy. However, whether affected testes contribute to fertility is unclear.
OBJECTIVES
To determine whether maximal tumor diameter (MTD) is correlated with ipsilateral fertility (IF) in patients treated for GCT.
METHODS
We reviewed medical charts for demographic and clinical data of patients with GCT who had undergone orchiectomy at our institution between 1999 and 2015. The extent of spermatogenesis was categorized into three groups: full spermatogenesis, hypospermatogenesis, and absence of spermatogenesis. The presence of mature spermatozoa in the epididymis tail was also assessed. We defined IF as the combination of full spermatogenesis in more than 100 tubules and the presence of mature spermatozoa in the epididymis tail. Mann-Whitney was applied to determine the correlation between MTD and IF.
RESULTS
Of 57 patients, IF was present in 28 (49%). Mean patient age was 32.8 years in patients with positive IF and 33.4 years those with negative IF. Seminoma was diagnosed in 46.4% of patients with positive IF and in 65.5% of patients with negative IF. Full spermatogenesis was observed in 33 patients (57.8%). In 48 (82.7%), mature epididymal spermatozoa were found. No correlation was found between MTD and IF.
CONCLUSIONS
IF is present in almost half of the patients undergoing radical orchiectomy. Because IF cannot be predicted by MTD, routine pre-orchiectomy sperm banking is suggested.
Topics: Adult; Epididymis; Fertility; Humans; Infertility, Male; Male; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Retrospective Studies; Seminoma; Spermatogenesis; Spermatozoa; Statistics, Nonparametric; Testicular Neoplasms; Testis
PubMed: 30324783
DOI: No ID Found -
Tumour Biology : the Journal of the... 2022CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for...
BACKGROUND
CA125 is the gold standard serum biomarker for monitoring patients with epithelial ovarian cancer (EOC). Human epididymal protein 4 (HE4) is a novel serum biomarker for EOC patients.
OBJECTIVE
The objective of this trial was to examine the utility of measuring serum HE4 levels for monitoring EOC patients and to compare HE4 performance parameters to serum CA125.
METHODS
A retrospective trial using residual longitudinal serum samples drawn during treatment and monitoring from EOC patients. Serum CA125 and HE4 levels were analyzed at each time point, and a velocity of change was calculated and correlated with clinical status. The null hypothesis was that HE4 is inferior to CA125, and this was tested using concordance and two-sided Fisher's exact testing. McNemar's test was used to assess the overall agreement of the two assays with the clinical status.
RESULTS
A total of 129 patients with 272 separate clinical periods and 1739 events (serum samples) were evaluated. Using a 25% change in serum biomarker levels to indicate change in disease status, the accuracy and NPV determined for HE4 versus CA125 were 81.8% versus 82.6% (p = 0.846) and 87.4% versus 89.7% (p = 0.082), respectively. Concordance comparison of HE4 accuracy / CA125 accuracy was 0.990, indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.522). Performing a velocity of change analysis, the accuracy and NPV determined for HE4 versus CA125 were 78.3% versus 78.6% (p = 0.995) and 74.9% versus 76.3% (p = 0.815), respectively. Concordance comparison of HE4 velocity accuracy / CA125 velocity accuracy was 0.996, again indicating HE4 was not inferior to CA125 (McNemar's test p-value = 0.884). The combination of HE4 and CA125 velocity changes showed a similar accuracy of 81.3% (p = 0.797 compared to HE4 and CA125 alone) and NPV of 81.1% (p≥0.172 compared to HE4 and CA125 alone), and an increased sensitivity of 70.5% (p≤0.070 compared to HE4 and CA125 alone).
CONCLUSION
HE4 is equivalent to CA125 for monitoring of EOC patients. The combination of CA125 and HE4 velocities is superior to either marker alone.
Topics: Biomarkers, Tumor; CA-125 Antigen; Carcinoma, Ovarian Epithelial; Female; Humans; Membrane Proteins; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Retrospective Studies
PubMed: 36189508
DOI: 10.3233/TUB-220016 -
The British Journal of General Practice... Jun 1997Since the late 1960s, vasectomy has been a popular and widely used form of contraceptive in Britain for couples who do not want to have any more children. However,... (Review)
Review
Since the late 1960s, vasectomy has been a popular and widely used form of contraceptive in Britain for couples who do not want to have any more children. However, throughout the past decade there has been considerable concern about the safety of this procedure. This paper reviews the current opinion on the possible health considerations associated with this operation and shows that the latest news is mostly reassuring.
Topics: Cardiovascular Diseases; Genital Diseases, Male; Humans; Male; Prostatic Neoplasms; Testicular Neoplasms; Vasectomy
PubMed: 9231476
DOI: No ID Found -
Journal of Cachexia, Sarcopenia and... Jun 2021Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for...
BACKGROUND
Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti-inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.
METHODS
The in vitro cell models of C2C12 myotube atrophy and 3T3-L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour-bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.
RESULTS
Carnosol and its analogues [dimethyl-carnosol (DCS) and dimethyl-carnosol-D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3-L1 adipocytes in vitro. Interestingly, CS and its analogues exhibited stronger inhibitive effects on muscle atrophy induced by tumour necrosis factor-α (TNF-α) (CS, P < 0.001; DCS, P < 0.001; DCSD, P < 0.001) in C2C12 myoblasts than on muscle atrophy induced by IL-6 (CS, P < 0.05; DCS, P = 0.08; DCSD, P < 0.05). In a C26 tumour-bearing mice model, administration of CS or its analogue DCSD significantly prevented body weight loss without affecting tumour size. At the end of the experiment, the body weight of mice treated with CS and DCSD was significantly increased by 11.09% (P < 0.01) and 11.38% (P < 0.01) compared with that of the C26 model group. CS and DCSD also improved the weight loss of epididymal adipose tissue in C26 model mice by 176.6% (P < 0.01) and 48.2% (P < 0.05) increase, respectively. CS and DCSD treatment partly preserved gastrocnemius myofibres cross-sectional area. CS treatment decreased the serum level of TNF-α (-95.02%, P < 0.01) but not IL-6 in C26 tumour-bearing mice. Inhibition on NF-κB and activation of Akt signalling pathway were involved in the ameliorating effects of CS and its analogues on muscle wasting both in vitro and in vivo. CS and its analogues also alleviated adipose tissue loss by inhibiting NF-κB and AMPK signalling pathways both in vitro and in vivo.
CONCLUSIONS
CS and its analogues exhibited anticachexia effects mainly by inhibiting TNF-α/NF-κB pathway and decreasing muscle and adipose tissue loss. CS and its analogues might be promising drug candidates for the treatment of cancer cachexia.
Topics: Abietanes; Animals; Cachexia; Lipolysis; Mice; Mice, Inbred BALB C; Muscular Atrophy; Neoplasms
PubMed: 33951335
DOI: 10.1002/jcsm.12710 -
Cancer Genomics & Proteomics 2023Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink...
BACKGROUND/AIM
Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC.
MATERIALS AND METHODS
Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS.
RESULTS
The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05).
CONCLUSION
In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Biomarkers, Tumor; Proteins; Neoplasms, Glandular and Epithelial; Membrane Glycoproteins
PubMed: 37093685
DOI: 10.21873/cgp.20380 -
Computational and Mathematical Methods... 2022This study was aimed at investigating the efficacy of PARP inhibitor combined with bevacizumab in the treatment of platinum-resistant recurrent ovarian epithelial...
OBJECTIVE
This study was aimed at investigating the efficacy of PARP inhibitor combined with bevacizumab in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma.
METHODS
A total of 84 patients with platinum-resistant recurrent ovarian epithelial carcinoma treated in our hospital from May 2017 to June 2018 were selected as the research objects. The patients were divided into observation group ( = 42) and control group ( = 42) according to random number table method. The observation group was treated with olaparib combined with bevacizumab, while the control group was treated with albumin-bound paclitaxel combined with bevacizumab, and the clinical efficacy of the two groups was observed. The levels of serum carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and epididymal protein 4 (HE4) were determined. The levels of miRNA124, mirNA-21, and miRNA-203 in the two groups were detected. The incidence of adverse reactions was compared between the two groups. The quality of life of the two groups was assessed using FACT-G scale. The drug safety of the two groups was observed. All patients were followed up for 3 years, and the survival time of the two groups was recorded. The Kaplan-Meier method was used to analyze the survival of the two groups.
RESULTS
The overall response rate (ORR) (69.05%) and disease control rate (DCR) (88.10%) of the observation group were higher than those of the control group (40.48% and 66.67%), and the differences were statistically significant (both < 0.05). After treatment, the levels of serum CA125, CA199, HE4, miRNA124, miRNA-21, and miRNA-203 and the improvement degree of quality of life score in the observation group were greater than those in the control group, with statistical significances (all < 0.05).The 1-year, 2-year, and 3-year survival rates of the observation group (97.62%, 88.10%, and 80.95%) were higher than those of the control group (71.43%, 57.14%, and 47.62%), with statistical significances (all > 0.05).
CONCLUSION
PARP inhibitor combined with bevacizumab had good effect in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma and can effectively improve the survival time and quality of life of patients.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carbohydrates; Carcinoma, Ovarian Epithelial; Female; Humans; MicroRNAs; Neoplasm Recurrence, Local; Ovarian Neoplasms; Platinum; Poly(ADP-ribose) Polymerase Inhibitors; Quality of Life
PubMed: 35720032
DOI: 10.1155/2022/4600145 -
Journal of Medical Case Reports May 2021Prostatic carcinoma is emerging as the most common male malignancy in Nigeria and the second most common male cancer worldwide. Patients often present with locally... (Review)
Review
BACKGROUND
Prostatic carcinoma is emerging as the most common male malignancy in Nigeria and the second most common male cancer worldwide. Patients often present with locally advances stages, and common sites of metastasis are the spine, pelvis, chest, and long bones. Metastases to the testes and spermatic cords are reputed to be rare and may be indicative of a worse outcome, when they occur. We recently encountered a clinical case of bilateral testicular, epididymal and spermatic cords prostatic cancer metastases.
CASE PRESENTATION
A 71-year-old Nigerian man, who presented at our hospital with 1-month-old complaints of inability to walk together with low back and bilateral thigh pains. This presentation had been preceded by a 5-month history of lower urinary tract symptoms. On examination, the prostate was hard and nodular as were the left testis and spermatic cord. On histological assessment of a needle biopsy, prostatic adenocarcinoma (Gleason score 5 + 5 = 10) was diagnosed. A subsequent therapeutic bilateral total orchidectomy specimen was found to contain metastatic prostatic carcinoma deposits, in the testes, epididymides, and spermatic cords. Although our patient is currently doing well postoperatively on zoledronic acid, ketoconazole, bicalutamide, and tamsulosin, he is being re-evaluated periodically for any feature of recurrence.
CONCLUSION
Since it has implications for eventual outcome, every clinically suspicious therapeutic orchidectomy specimen should be subjected to a detailed histopathological examination in order to exclude secondaries from the primary prostatic malignancy.
Topics: Adenocarcinoma; Aged; Carcinoma; Humans; Infant; Male; Neoplasm Recurrence, Local; Nigeria; Prostate; Prostatic Neoplasms; Spermatic Cord; Testicular Neoplasms
PubMed: 33931116
DOI: 10.1186/s13256-021-02807-4 -
Journal of the Royal Society of Medicine Sep 1985Scrotal ultrasonography has been performed in 105 men with a variety of intrascrotal conditions. The range of pathology interpreted by this technique is presented and...
Scrotal ultrasonography has been performed in 105 men with a variety of intrascrotal conditions. The range of pathology interpreted by this technique is presented and its diagnostic accuracy evaluated. The clinical application and usefulness of this noninvasive method of imaging scrotal contents is discussed.
Topics: Adult; Aged; Epididymitis; Genital Diseases, Male; Hematoma; Humans; Male; Middle Aged; Orchitis; Scrotum; Testicular Diseases; Testicular Neoplasms; Ultrasonography
PubMed: 3900400
DOI: 10.1177/014107688507800904