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BMJ Open Oct 2023Bone is one of the most common target sites for advanced tumours. The objective was to survey the prevalence and prognosis of bone metastases in 12 common solid...
OBJECTIVE
Bone is one of the most common target sites for advanced tumours. The objective was to survey the prevalence and prognosis of bone metastases in 12 common solid malignant tumours.
DESIGN
A retrospective cohort study.
METHODS
A total of 1 425 332 patients with a primary cancer between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. We computed the prevalence and prognosis of bone metastases in each cancer and compared their survival in different stages. The Kaplan-Meier method and Cox logistic regression were used to analyse survival and quantify the effect of bone metastases.
RESULTS
This study included 89 782 patients with bone metastases at diagnosis. Lung cancer had the highest prevalence (18.05%), followed by liver cancer (6.63%), nasopharyngeal carcinoma (6.33%) and renal cancer (5.45%). Breast cancer (32.1%), prostate cancer (25.9%), thyroid cancer (46.9%) and nasopharyngeal carcinoma (24.8%) with only bone metastases had a 5-year survival rate of over 20%. Compared with patients at the stage previous to metastasis, bone metastases significantly increased the risk of mortality and decreased survival, especially for those with prostate cancer (adjusted HR: 18.24). Other concomitant extraosseous metastases worsened patient survival. Bone was the most common site of metastasis for prostate cancer, while for colorectal cancer, multiorgan metastases were predominant.
CONCLUSIONS
This study provides the prevalence and prognosis of bone metastases at the initial diagnosis of common solid cancers. In addition, it demonstrates the impact of bone metastases on survival. These results can be used for early screening of metastases, clinical trial design and assessment of prognosis.
Topics: Male; Humans; Prevalence; Nasopharyngeal Carcinoma; Retrospective Studies; SEER Program; Kaplan-Meier Estimate; Bone Neoplasms; Prognosis; Prostatic Neoplasms; Nasopharyngeal Neoplasms
PubMed: 37865405
DOI: 10.1136/bmjopen-2022-069908 -
BMC Cancer Mar 2024Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles... (Review)
Review
Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.
Topics: Male; Humans; Adenocarcinoma; Pancreatic Neoplasms; Extracellular Vesicles; Exosomes; MicroRNAs; Biomarkers; DNA; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 38454346
DOI: 10.1186/s12885-024-11819-4 -
Molecular Cancer Research : MCR May 2024Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into...
UNLABELLED
Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa.
IMPLICATIONS
Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.
Topics: Humans; Male; Proteome; Animals; Mice; Phosphoproteins; Prostatic Neoplasms, Castration-Resistant; Heterografts; Prostatic Neoplasms; Adenocarcinoma; Xenograft Model Antitumor Assays; Proteomics
PubMed: 38345532
DOI: 10.1158/1541-7786.MCR-23-0976 -
Medicine Sep 2023Endometrioid carcinoma (EC) and clear cell carcinoma (CC) are associated with endometrial tissue hyperplasia and endometriosis, and they occur in the endometrium and...
Endometrioid carcinoma (EC) and clear cell carcinoma (CC) are associated with endometrial tissue hyperplasia and endometriosis, and they occur in the endometrium and ovaries. However, detailed differences between these tumors based on immunostaining are unclear; therefore, in this study, we aimed to analyze the clinicopathological correlations between these tumors using immunostaining and to develop new treatments based on histological subtypes. Immunohistochemistry was used to investigate differentially expressed hypoxia-associated molecules (hypoxia-inducible factor-1 subunit alpha [HIF-1α], forkhead box O1, prostate-specific membrane antigen, signal transducer and activator of transcription 3 [STAT3], hepatocyte nuclear factor 1β [HNF-1β], aquaporin-3, and vimentin [VIM]) between these carcinomas because of the reported association between CC and ischemia. Immunostaining and clinicopathological data from 70 patients (21 uterine endometrioid carcinomas [UECs], 9 uterine cell carcinomas, 20 ovarian endometrioid carcinomas [OECs], and 20 ovarian cell carcinomas [OCCs]) were compared. HIF-1α and prostate-specific membrane antigen expression levels were higher in UEC and OCC than in uterine cell carcinomas and OEC. STAT3 was slightly overexpressed in UEC. Additionally, forkhead box O1 expression was either absent or significantly attenuated in all ECs. VIM and AQ3 were highly expressed in UEC, whereas HNF-1β expression was higher in OCC. UEC, OEC, and OCC were more common in the uterine fundus, left ovary, and right ovary, respectively. Ovarian endometriosis was strongly associated with EC. Our findings suggest that UEC and OCC share a carcinogenic pathway that involves HIF-1α induction under hypoxic conditions via STAT3 expression, resulting in angiogenesis. Furthermore, the anatomical position of carcinomas may contribute to their carcinogenesis. Finally, aquaporin-3 and VIM demonstrate strong potential as biomarkers for UEC, whereas HNF-1β expression is a crucial factor in CC development. These differences in tumor site and histological subtypes shown in this study will lead to the establishment of treatment based on histological and immunohistological classification.
Topics: Female; Male; Humans; Hepatocyte Nuclear Factor 1-beta; Carcinoma, Endometrioid; Endometriosis; Uterus; Endometrium; Ovarian Neoplasms; Adenocarcinoma, Clear Cell; Endometrial Hyperplasia; Aquaporins
PubMed: 37713813
DOI: 10.1097/MD.0000000000035301 -
BMC Urology Sep 2023To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers.
OBJECTIVE
To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers.
METHODS
This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers.
RESULTS
A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P < 0.01) differences between the MetS and non-MetS groups (0.70% vs. 0.48%, 0.27% vs. 0.15%, and 0.22% vs. 0.13%, respectively). Compared to the non-MetS group, the risk of developing urologic [HR (95% CI) = 1.29 (1.08-1.55)], kidney [HR (95% CI) = 1.74 (1.28-2.37)], and prostate [HR (95% CI) = 1.47 (1.04-2.07)] cancers was significantly higher in the MetS group. In the MetS group, elevated BP increased the risk of developing of urologic cancer [HRs (95% CI) = 1.35 (1.10-1.66)] and kidney cancer [HR (95% CI) = 1.74 (1.21-2.51)], while central obesity increased the risk of developing prostate cancer [HR (95% CI) = 1.68 (1.18-2.40)].
CONCLUSIONS
MetS increased the risk of developing urologic, kidney, and prostate cancers but had no association with the development of bladder cancer.
Topics: Male; Humans; Metabolic Syndrome; Prospective Studies; Urologic Neoplasms; Urinary Bladder Neoplasms; Kidney Neoplasms; Prostatic Neoplasms; Carcinoma, Renal Cell
PubMed: 37736725
DOI: 10.1186/s12894-023-01324-4 -
Cancers Feb 2024This comprehensive review critically examines the transformative impact of artificial intelligence (AI) and radiomics in the diagnosis, prognosis, and management of... (Review)
Review
This comprehensive review critically examines the transformative impact of artificial intelligence (AI) and radiomics in the diagnosis, prognosis, and management of bladder, kidney, and prostate cancers. These cutting-edge technologies are revolutionizing the landscape of cancer care, enhancing both precision and personalization in medical treatments. Our review provides an in-depth analysis of the latest advancements in AI and radiomics, with a specific focus on their roles in urological oncology. We discuss how AI and radiomics have notably improved the accuracy of diagnosis and staging in bladder cancer, especially through advanced imaging techniques like multiparametric MRI (mpMRI) and CT scans. These tools are pivotal in assessing muscle invasiveness and pathological grades, critical elements in formulating treatment plans. In the realm of kidney cancer, AI and radiomics aid in distinguishing between renal cell carcinoma (RCC) subtypes and grades. The integration of radiogenomics offers a comprehensive view of disease biology, leading to tailored therapeutic approaches. Prostate cancer diagnosis and management have also seen substantial benefits from these technologies. AI-enhanced MRI has significantly improved tumor detection and localization, thereby aiding in more effective treatment planning. The review also addresses the challenges in integrating AI and radiomics into clinical practice, such as the need for standardization, ensuring data quality, and overcoming the "black box" nature of AI. We emphasize the importance of multicentric collaborations and extensive studies to enhance the applicability and generalizability of these technologies in diverse clinical settings. In conclusion, AI and radiomics represent a major paradigm shift in oncology, offering more precise, personalized, and patient-centric approaches to cancer care. While their potential to improve diagnostic accuracy, patient outcomes, and our understanding of cancer biology is profound, challenges in clinical integration and application persist. We advocate for continued research and development in AI and radiomics, underscoring the need to address existing limitations to fully leverage their capabilities in the field of oncology.
PubMed: 38398201
DOI: 10.3390/cancers16040810 -
Scientific Reports Dec 2023Progress in immunotherapy for prostate cancer (PCa) lags that for other cancers, mainly because of limited immune infiltration in PCa. This study aimed to assess the...
Progress in immunotherapy for prostate cancer (PCa) lags that for other cancers, mainly because of limited immune infiltration in PCa. This study aimed to assess the feasibility of NSD2 as an immunotherapeutic target in PCa. Immunohistochemistry was performed to evaluate the expression pattern of NSD2 in 34 cases of benign prostatic hyperplasia (BPH), 36 cases of prostatic intraepithelial neoplasia (PIN), and 57 cases of PCa, including 19 cases of metastatic castration-resistant prostatic cancer (mCRPC). Single-cell RNA sequencing and gene set enrichment analysis (GSEA) were used to correlate NSD2 with certain downstream pathways. Furthermore, the Immuno-Oncology-Biological-Research (IOBR) software package was used to analyze the potential roles of NSD2 in the tumor microenvironment. We found that the positive expression rate of NSD2 increased progressively in BPH, PIN and PCa. mCRPC had the highest staining intensity for NSD2. High NSD2 expression was positively correlated with the infiltration level of CD4 tumor-infiltrating lymphocytes (TILs) and negatively correlated with that of CD8 TILs. Importantly, a new immune classification based on NSD2 expression and CD4 TILs and CD8 TILs was successfully used to stratify PCa patients based on OS.PSA and CD4 TILs are independent risk factors for PCa bone metastasis. This study demonstrates a novel role for NSD2 in defining immune infiltrate on in PCa and highlights the great potential for its application in immunotherapy response evaluation for prostate malignancies.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Prostatic Hyperplasia; T-Lymphocytes; Prostatic Neoplasms; Prognosis; Prostatic Intraepithelial Neoplasia; Lymphocytes, Tumor-Infiltrating; Tumor Microenvironment
PubMed: 38062230
DOI: 10.1038/s41598-023-48906-8 -
Annals of Medicine and Surgery (2012) Sep 2023The extent of surgical resection in orthopedic oncology differs according to tumor biology. While malignant bone tumors are operatively managed with wide resection,...
INTRODUCTION
The extent of surgical resection in orthopedic oncology differs according to tumor biology. While malignant bone tumors are operatively managed with wide resection, benign bone tumors and metastatic carcinomas are often treated through intralesional excision and adjuvant modalities, including the elimination of residual neoplastic cells through thermal necrosis. This study investigates in vitro temperature thresholds for thermal necrosis in common orthopedic bone tumors.
METHODOLOGY
Eleven cell lines, including metastatic carcinomas to bone (A549, A498, FU-UR-1, PC3, MDA-MB-231, TT, MCF7, and K1), giant cell tumor of bone, osteosarcoma (HG-63), and control non-neoplastic cells (HEK293) were cultured. Cells were exposed to thermal stress at varying times and temperatures and evaluated for survival and viability with crystal violet and MTT assays.
RESULTS
Both the MTT and crystal violet assay demonstrated statistically superior rates of viability and survival for A549 (lung carcinoma), FU-UR-1 (renal carcinoma), K1 (thyroid carcinoma), and MG-63 (osteosarcoma) cell lines compared to control (HEK293 cells) at 60°C. Additionally, the MTT assay demonstrated superior viability for PC3 (prostate carcinoma), MCF7 (breast carcinoma), and A498 (renal carcinoma) compared to control. All cell lines demonstrated significantly decreased survival and viability in temperatures more than 90°C.
CONCLUSION
This study demonstrated in vitro thresholds for thermal necrosis for cell lines of common orthopedic tumors of bone. The A549 (lung carcinoma), K1 (thyroid carcinoma), and FU-UR-1 (renal carcinoma) cell lines demonstrated greater resistance to heat stress compared to non-neoplastic control cells. Temperatures in excess of 90°C are necessary to reliably reduce cell survival and viability to less than 10%.
PubMed: 37663713
DOI: 10.1097/MS9.0000000000001052 -
JAMA Network Open Oct 2023Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.
OBJECTIVE
To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required.
INTERVENTIONS
Oral selenium (200 μg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo.
MAIN OUTCOME AND MEASURES
Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022).
RESULTS
The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required.
TRIAL REGISTRATION
isrctn.org Identifier: ISRCTN13889738.
Topics: Humans; Male; Aged; Vitamin E; Selenium; Non-Muscle Invasive Bladder Neoplasms; Prospective Studies; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 37847504
DOI: 10.1001/jamanetworkopen.2023.37494 -
Frontiers in Oncology 2023Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is...
INTRODUCTION
Cell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors.
METHODS
To investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing.
RESULTS
RNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an age-dependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score.
CONCLUSION
Overall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14.
PubMed: 37671061
DOI: 10.3389/fonc.2023.1212585