Endobronchial metastases 20 years after prostate cancer excision.
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ABSTRACT:
SUBMITTER: Hatakeyama Y
PROVIDER: S-EPMC6538950 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The occurrence of endotracheal/endobronchial metastasis (EEM) after complete resection of a primary lung cancer is rare. Here, we report the case of an 86-year-old woman in whom EEM occurred twice over a 20-year period following complete resection of a primary adenocarcinoma localized to the left main bronchus and trachea. The presence of EEM was confirmed by establishing immunohistochemical homology of the metastases with the primary tumor. To the best of our knowledge, this is the first reported case of repetitive EEM of primary lung adenocarcinoma. Lymphatic invasion in the primary lesion suggested that a possible route for EEM was the peripheral lymphatic tract, explaining the slow recurrence rate. We conclude that observation of the trachea/bronchus over a long period post operation could be important in monitoring for EEM, particularly if lymphatic invasion is confirmed in the primary tumor.
| S-EPMC7779200 | biostudies-literature
Project description:STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC.Patient summaryWe studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs.
| S-EPMC5624794 | biostudies-literature
Project description:Background & objectivesGenetic variation in the DNA repair genes might be associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited polymorphisms may increase the susceptibility to cancers. Base excision and nucleotide excision are the two major repair pathways. We investigated the association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon 7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with risk of prostate cancer (PCa).MethodsThe study was designed with 192 histopathologically confirmed PCa patients and 224 age matched healthy controls of similar ethnicity. Genotypes were determined by amplification refractory mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP) methods.ResultsOverall, a significant association in NER gene, XPC PAT Ins/Ins (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33, P=0.012). XPC exon 15 variant CC genotypes presented statistically significant risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no association was observed for polymorphism with BER genes. Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa. The variant genotypes of NER genes were also associated with high Gleason grade.Interpretation & conclusionsThe results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.
| S-EPMC3307187 | biostudies-literature
Project description:ObjectiveDespite a multitude of detection and treatment advances in the past 2 decades, prostate cancer remains the second leading cause of deaths due to cancer among men in the United States. Technological evolution and expanding knowledge of tumor biomarkers have invigorated exploration in prostate cancer therapeutics. Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer biomarkers successfully cloned. Since then, it has been characterized as the prototypical cell-surface marker for prostate cancer and has been the subject of intense clinical inquiry. In this article, we review the relevant research in PSMA on the 20th anniversary of its cloning.Methods and materialsA PubMed search using the keywords "prostate-specific membrane antigen" or "glutamate carboxypeptidase II" provided 1019 results. An additional 3 abstracts were included from scientific meetings. Articles were vetted by title and abstract with emphasis placed on those with clinically relevant findings.ResultsSixty articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its structure and function were further delineated in the ensuing decade. Consensus sites of expression in normal physiology are prostate, kidney, nervous system, and small intestine. PSMA has been implicated in the neovasculature of several tumors including urothelial and renal cell carcinomas. In prostate cancer, expression of PSMA is directly related to the Gleason grade. PSMA has been tested both in imaging and therapeutics in a number of prostate cancer clinical trials. Several recent approaches to target PSMA include the use of small molecule inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted prodrug therapy. Future study of PSMA in prostate cancer might focus on its intracellular functions and possible role in tumor neurogenesis.ConclusionsTwenty years from its discovery, PSMA represents a viable biomarker and treatment target in prostate cancer. Research to delineate its precise role in prostate carcinogenesis and within the therapeutic armamentarium for patients with prostate cancer remains encouraging.
| S-EPMC3972351 | biostudies-literature
Project description:Bone metastasis is the major deleterious event in prostate cancer (PCa). TMPRSS2-ERG fusion is one of the most common chromosomic rearrangements in PCa. However, its implication in bone metastasis development is still unclear. Since bone metastasis starts with the tropism of cancer cells to bone through specific migratory and invasive processes involving osteomimetic capabilities, it is crucial to better our understanding of the influence of TMPRSS2-ERG expression in the mechanisms underlying the bone tropism properties of PCa cells. We developed bioluminescent cell lines expressing the TMPRSS2-ERG fusion in order to assess its role in tumor growth and bone metastasis appearance in a mouse model. First, we showed that the TMPRSS2-ERG fusion increases cell migration and subcutaneous tumor size. Second, using intracardiac injection experiments in mice, we showed that the expression of TMPRSS2-ERG fusion increases the number of metastases in bone. Moreover, TMPRSS2-ERG affects the pattern of metastatic spread by increasing the incidence of tumors in hind limbs and spine, which are two of the most frequent sites of human PCa metastases. Finally, transcriptome analysis highlighted a series of genes regulated by the fusion and involved in the metastatic process. Altogether, our work indicates that TMPRSS2-ERG increases bone tropism of PCa cells and metastasis development.
| S-EPMC5355307 | biostudies-literature
Project description:Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents.
| S-EPMC4807885 | biostudies-literature
Project description:Recent studies suggest that hereditary prostate cancer is a complex disease involving multiple susceptibility genes and variable phenotypic expression. While conducting a genomewide search on 162 North American families with > or =3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromosome 20q13 with two-point parametric LOD scores >1 at multiple sites, with the highest two-point LOD score of 2.69 for marker D20S196. The maximum multipoint NPL score for the entire data set was 3.02 (P=.002) at D20S887. On the basis of findings from previous reports, families were stratified by the presence (n=116) or absence (n=46) of male-to-male transmission, average age of diagnosis (<66 years, n=73; > or =66 years, n=89), and number of affected individuals (<5, n=101; > or =5, n=61) for further analysis. The strongest evidence of linkage was evident with the pedigrees having <5 family members affected with prostate cancer (multipoint NPL 3.22, P=.00079), a later average age of diagnosis (multipoint NPL 3.40, P=.0006), and no male-to-male transmission (multipoint NPL 3.94, P=.00007). The group of patients having all three of these characteristics (n=19) had a multipoint NPL score of 3.69 (P=.0001). These results demonstrate evidence for a PRCA susceptibility locus in a subset of families that is distinct from the groups more likely to be linked to previously identified loci.
| S-EPMC1287105 | biostudies-literature
Project description:Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.
| S-EPMC8121836 | biostudies-literature
Project description:PurposeThe incidence of localized prostate cancer has decreased with shifts in prostate cancer screening. While recent population based studies demonstrated a stable incidence of locoregional prostate cancer, they categorized organ confined, extraprostatic and lymph node positive disease together. However, to our knowledge the contemporary incidence of prostate cancer with pelvic lymph node metastases remains unknown.Materials and methodsWe used SEER (Surveillance, Epidemiology and End Results) data from 2004 to 2014 to identify men diagnosed with prostate cancer. We analyzed trends in the age standardized prostate cancer incidence by stage. The impact of disease extent on mortality was assessed by adjusted Cox proportional hazard analysis.ResultsDuring the study period the annual incidence of nonmetastatic prostate cancer decreased from 5,119.1 to 2,931.9 per million men (IR 0.57, 95% CI 0.56-0.58, p <0.01) while the incidence of pelvic lymph node metastases increased from 54.1 to 79.5 per million men (IR 1.47, 95% CI 1.33-1.62, p <0.01). The incidence of distant metastases in men 75 years old or older reached a nadir in 2011 compared to 2004 (IR 0.81, 95% CI 0.74-0.90, p <0.01) and it increased in 2012 compared to 2011 (IR 1.13, 95% CI 1.02-1.24, p <0.05). The risk of cancer specific mortality significantly increased in men diagnosed with pelvic lymph node metastases (HR 4.5, 95% CI 4.2-4.9, p <0.01) and distant metastases (HR 21.9, 95% CI 21.2-22.7, p <0.01) compared to men with nonmetastatic disease.ConclusionsThe incidence of pelvic lymph node metastases is increasing coincident with a decline in the detection of localized disease. Whether this portends an increase in the burden of advanced disease or simply reflects decreased lead time remains unclear. However, this should be monitored closely as the increase in N1 disease reflects an increase in incurable prostate cancer at diagnosis.
| S-EPMC6530582 | biostudies-literature
Project description:Medical oncology is moving toward personalized and precision treatments. This evolution is spearheaded by ongoing discoveries on the fundamental machinery that controls tumor and hosts microenvironment biological behavior. α-Particles with their high energy and short range had long been recognized as potentially useful in the treatment of cancer. More than a century after the discovery of radium by the Curies, 223Ra dichloride is now available in the expanding armamentarium of therapies for metastatic castration-resistant prostate cancer. This advance occurs in the context of several other novel therapeutics in advanced prostate cancer that include more effective androgen receptor pathway inhibition, better chemotherapy, and immunotherapy. We present a concise review on the therapeutic use of 223Ra dichloride in this clinically important setting including excerpts on the radium history, physical properties, the alpharadin in symptomatic prostate cancer clinical trial, and practical information on its use in the clinic. It is anticipated that, with the current emergence of 223Ra as a viable form of therapy, interest in and use of α-particle therapy in the management of cancer will grow.
| S-EPMC3874447 | biostudies-literature