Trends in treatments for prostate cancer in the United States, 2010-2015

xlomafota13 shared this article with you from Inoreader Trends in treatments for prostate cancer in the United States, 2010-2015 Via American Journal of Cancer Research Am J Cancer Res. 2021 May 20;11(5):2351-2368. eCollection 2021. ABSTRACT Although annual mortality trends for prostate cancer were stabilized in recent years, understanding the exact treatment changes is necessary for optimal management. Utilization of not-otherwise specified (NOS) treatments for prostate cancer was unclear. Thus, this study aimed to analyze trends in treatment for prostate cancer in the U.S. from 2010 to 2015 and examine whether the treatment for the prostate cancer in the U.S. is compliant with clinical practice guidelines. Using joinpoint regression models, we examined trends in the rate and proportion of age-standardized utilization (ASUR and ASUP) of treatments for prostate cancer diagnosed during 2010-2015 in the U.S. based on the data from the Surveillance, Epidemiology, and End Results (SEER, 2018 data-release, with linkage to active surveillance/watchful waiting [AS/WW]) cancer registry program. Among 316,690 men with prostate cancer diagnosed during 2010-2015, ASUR and ASUP for radical prostatectomy, radiotherapy, AS/WW and NOS treatment were 32.7, 34.4, 10.0 and 40.1 per 100,000, and 27.9%, 29.3%, 8.5% and 34.2%, respectively. Trends in the overall ASUR for prostate cancer treatments differed by cancer risk group, patients' age, race/ethnicity, Gleason score, insurance status, and the average education level, average poverty-level and foreign-born person percentage of the patient's residence-county, but not by rural-urban continuum or region. ASUP of radical prostatectomy decreased from 9.8% in 2010 to 4.8% in 2015 (annual percent change [APC] = -12.0%, 95% CI, -15.9 to -7.9%), and the decrease was observed in all different risk groups. ASUP of AS/WW increased from 16.4% in 2010 to 30.2% in 2013 (APC = 22.7%, 95% CI, 4.6 to 44.0%) and then remained stable through 2013 to 2015 (APC = 1.9%, 95% CI, -24.1 to 36.9%). The increasing tendency of AS/WW only occurred in the low-risk and interm ediate-risk groups. The ASUP of NOS treatment has increased from 32.3% in 2010 to 36.8% in 2015 (P<0.01). In conclusion, ASUR and ASUP for prostate cancer treatments, including NOS treatment, had changed during 2010-2015. Their trends appeared to differ by cancer risk-group, age, race/ethnicity, Gleason score and socioeconomic factors. Future studies are warranted to understand the impacts of upward trends in ASUP of NOS treatments and AS/WW on patient survival and prostate cancer mortality. PMID:34094691 | PMC:PMC8167696 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin

xlomafota13 shared this article with you from Inoreader Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2303-2311. eCollection 2021. ABSTRACT Mitochondria have attracted attention in cancer research as organelles associated with tumor development and response to therapy. We recently reported acquisition of resistance to cisplatin (DDP) associated with a metabolic rewiring in ovarian cancer patient-derived xenografts (PDXs) models. DDP-resistant PDXs models were obtained mimicking the clinical setting, treating mice bearing sensitive-DDP tumors with multiple cycles of DDP until the development of resistance. To further characterize the metabolic rewiring, the present study focused on tumor mitochondria. We analysed by transmission electron microscopy the mitochondria structure in two models of DDP-resistant and the corresponding DDP-sensitive PDXs and evaluated tumor mDNA content, the expression of genes and proteins involved in mitochondria functionality, and mitochondria fitness-related processes, such as autophagy. We observed a decrease in the number of mitochondria paralleled by an increased volume in DDP-resistant versus DDP-sensitive PDXs. DDP-resistant PDXs presented a higher percentage of damaged mitochondria, in particular of type 2 (concave-shape), and type 3 (cristolysis) damage. We found no difference in the mDNA content, and the expression of genes involved in mitochondrial biogenesis was similar between the sensitive and resistant PDXs. An upregulation of some genes involved in mitochondrial fitness in DDP-R versus DDP-S PDXs was observed. At protein level, no difference in the expression of proteins involved in mitochondrial function and biogenesis, and in autophagy/mitophagy was found. We here reported that the acquisition of DDP resistance is associated with morphological alterations in mitochondria, even if we couldn't find any dysregulation in the studied genes/proteins that could explain the observed differences. PMID:34094686 | PMC:PMC8167697 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Regional lymph nodes distribution pattern in central area of right-sided colon cancer: in-vivo detection and the update on the clinical exploration

xlomafota13 shared this article with you from Inoreader Regional lymph nodes distribution pattern in central area of right-sided colon cancer: in-vivo detection and the update on the clinical exploration Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2095-2105. eCollection 2021. ABSTRACT Distribution of regional lymph nodes (LNs) is decisive for the lymphadenectomy boundary in radical resection of right-sided colon cancer (RCC). Currently, the data of LNs in central area remains ambiguous and scarce. Herein we aim to provide a more detailed anatomical research on LNs surrounding the superior mesenteric vessels for RCC and investigated the metastasis rate. In this study, Carbon Nanoparticles (CNs) and Indocyanine Green (ICG) were used for regional LNs mapping by preoperative colonoscopic tattooing (PCT) and we laparoscopically observed the stained LNs distribution pattern. Lastly, 143 RCC patients who received a "superior mesenteric artery (SMA)-oriented" hemicolectomy were included to calculate the probability of LNs metastasis in our target area. 27 patients diagnosed as RCC (mean age 58.04 years, 17 male) were included. 14 patients underwent CNs injection and 13 patients consented to the ICG, while 4 cases suffered from imaging failure. The unequal number of the regional LNs located between SMV and SMA was detected in 22 cases (81.48%), posterior to SMV area in 6 cases (22.22%), and anterior to SMA in 16 cases (59.26%), respectively. The presence of LNs posterior to SMV was associated with the crossing pattern of ileocolic artery (χ2 = 4.24, P = 0.039). The probability of LNs metastasis in the above areas (target areas) was 2.10% (3/143). In conclusion, right-hemi colon-draining lymphatic vessels anteriorly/posteriorly traversed the SMV and arrived at the surface of SMA near the middle colonic artery (MCA) level, which highlights the potential need of removing mesenteric tissue in our target area on lymphatic resection. PMID:34094671 | PMC:PMC8167669 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cumulative total S-1 dose in adjuvant chemotherapy affects the long-term outcome following curative gastrectomy for gastric cancer

xlomafota13 shared this article with you from Inoreader Cumulative total S-1 dose in adjuvant chemotherapy affects the long-term outcome following curative gastrectomy for gastric cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2312-2318. eCollection 2021. ABSTRACT A recent JCOG1104, OPAS-1 trial revealed the significance of S-1 duration. However, the significance of cumulative total S-1 dose (CTSD) remains unclear. In this study, we designed to evaluate the prognostic effect of CTSD on adjuvant chemotherapy after curative gastrectomy. We retrospectively analyzed 77 consecutive pStage II and III gastric cancer (GC) patients, who underwent curative gastrectomy followed by adjuvant S-1 chemotherapy from 2008 through 2014. CTSD of 20000 mg was the upper-limit of cut-off value to stratify the prognosis (5-year relapse free survival (RFS); CTSD < 20000 mg vs. CTSD ≥ 20000 mg: 51.9% vs. 85.1%, P = 0.004). Compared patients with CTSD more than 20000 mg, those with CTSD less than 20000 mg had a significantly higher rate of preoperative anemia (P = 0.041), low nutrition (P = 0.008) and open gastrectomy (P = 0.012). Multivariate Cox's proportional hazards model for RFS proved that CTSD less than 20000 mg was an independent prognostic factor [P = 0.031, HR 3.32 (95% CI: 1.11-11.1)] although S-1 intensity and duration were not independent prognostic factors. The cumulative total S-1 dose more than 20000 mg might contribute to better prognosis. PMID:34094687 | PMC:PMC8167698 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The role of liver sinusoidal endothelial cells in cancer liver metastasis

xlomafota13 shared this article with you from Inoreader The role of liver sinusoidal endothelial cells in cancer liver metastasis Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):1845-1860. eCollection 2021. ABSTRACT Liver sinusoidal endothelial cells (LSECs) are the gatekeeper cells in the liver, contributing critical roles in liver physiological and pathological changes. Factors such as dietary macronutrients, toxins, and aging impact LSEC fenestration. Defenestration of LSECs changes their phenotype and function. Under liver injury, capillarized LSECs promote hepatic stellate cells (HSCs) activation and fibrogenesis, while decapillarized LSECs protect the activation of HSCs and liver injury. The expression of chemokines, such as CXCL9 and CXCL16, changes and impacts the infiltration of immune cells in the liver during disease progression, including hepatocellular carcinoma (HCC). As the largest solid organ, liver is one of the most favorable organs into where tumor cells metastasize. The increased interaction and adhesion of circulating tumor cells (CTCs) with LSECs in the local microenvironment and LSEC-induced tolerance of immunity promote cancer liver metastasis. Several strategies can be applied to target LSEC to modulate their function to prevent cancer liver metastasis, including gut microbiota modulation, microRNA therapy, and medical treatment. Delivery of different treatment agents with nanoparticles may promote precise target treatment. Overall, targeting LSECs is a potential strategy for treatment of early liver diseases and prevention of cancer liver metastasis. PMID:34094657 | PMC:PMC8167702 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Alpha-fetoprotein response at different time-points is associated with efficacy of nivolumab monotherapy for unresectable hepatocellular carcinoma

xlomafota13 shared this article with you from Inoreader Alpha-fetoprotein response at different time-points is associated with efficacy of nivolumab monotherapy for unresectable hepatocellular carcinoma Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2319-2330. eCollection 2021. ABSTRACT Nivolumab monotherapy has a modest objective response rate (ORR) in hepatocellular carcinoma (HCC). To overcome the lack of biomarkers that predict delayed alpha-fetoprotein (AFP) response beyond 4 weeks, we applied a novel 50-10 rule of AFP response for unresectable HCC patients under nivolumab monotherapy and proposed an algorithm based on on-treatment AFP reduction at different time-points. Ninety unresectable HCC patients who underwent nivolumab monotherapy in 2015-2019 were retrospectively recruited and divided into four classes: rapid AFP decrease of ≥ 50% of baseline at week 4 (class I), AFP changes within ± 50% of baseline at week 4 that later decreased to ≥ 10% of baseline (class II) or not (class III) at week 12, and rapid AFP increase of ≥ 50% of baseline at week 4 (class IV). ORR was 47.4%, 36.0%, 7.7%, and 5.0% in class I-IV patients, respectiv ely. Rapid (class I) and delayed (class II) AFP responders had significantly higher ORR, overall survival (OS) and progression-free survival (PFS) than non-responders (class III and IV) (ORR: 40.9% vs. 6.5%, P<0.001; median OS: not reached vs. 9.6 months, log-rank P<0.001; median PFS: 9.6 vs. 2.8 months, log-rank P<0.001). In multivariate analysis, AFP response was an independent factor associated with good OS (hazard ratio [HR]=0.301, P=0.001) and PFS (HR=0.332, P<0.001). Moreover, AFP responders had higher ORR and better OS as well as PFS than non-responders, regardless of nivolumab as a first- or more than a second-line therapy (all P<0.05). In conclusion, the novel 50-10 rule of AFP response provides practical guidance for nivolumab monotherapy in unresectable HCC patients. However, this algorithm remains to be verified in a large prospective cohort. PMID:34094688 | PMC:PMC8167682 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling

xlomafota13 shared this article with you from Inoreader βKlotho, a direct target of miR-206, contributes to the growth of hepatoblastoma through augmenting PI3K/Akt/mTOR signaling Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):1982-2004. eCollection 2021. ABSTRACT Hepatoblastoma (HB) is the most frequent pediatric liver malignancy. However, the treatment outcome for patients with advanced-stage HB remains unsatisfactory. Accumulating evidence indicates that βKlotho (KLB) acts as an oncogene or a tumor-suppressor gene in a context-dependent manner. Despite this, the expression profile and effects of KLB on the growth of HB are still elusive. This study aimed to explore the effect of miR-206/KLB axis on HB growth. The expression of KLB was explored in HB cells (HepG2 and HuH6) and tissues using quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunohistochemistry. Besides, miR-206 expression was determined in HB cells and tissues using qPCR and fluorescence in situ hybridization. The prognostic value of KLB or miR-206 in our patients with HB was investigated using the Kaplan-Meier method. The biologi cal effects of KLB or miR-206 on HB cells were identified in vitro. The proliferative effects of KLB on HuH6 cells were also investigated in vivo. Moreover, the mechanical signaling of KLB in HB was determined through bioinformatics analysis followed by experimental validation. The results showed a significant upregulation of KLB in HB tissues and cells. Elevated level of KLB was found to be significantly correlated with the aggressive phenotype and poor overall survival for children with HB. The in vitro function assay demonstrated that KLB knockdown promoted apoptosis and suppressed the proliferation, migration, and invasion of HB cells. Besides, KLB knockdown inhibited the proliferation of HuH6 cells in vivo, while KLB overexpression had the opposite effect. Furthermore, KLB was proved to be the direct target of miR-206. Low level of miR-206 served as an independent risk factor for poor prognosis in children with HB. The overexpression of miR-206 negat ively regulated the aggressive biological behaviors of HB cells, which was partially rescued by KLB overexpression. Mechanically, the miR-206/KLB axis played a vital role in HB growth through augmenting the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling. In conclusion, the data demonstrated that the miR-206/KLB axis might serve as an important biomarker/therapeutic target for HB. PMID:34094665 | PMC:PMC81676 75 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer

xlomafota13 shared this article with you from Inoreader Association between the polygenic liabilities for prostate cancer and breast cancer with biochemical recurrence after radical prostatectomy for localized prostate cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2331-2342. eCollection 2021. ABSTRACT Prostate and breast cancers are hormone-related malignancies and are characterized by a complex interplay of hundreds of susceptibility loci throughout the genome. Prostate cancer could be inhibited by eliminating androgens through castration or estrogen administration, thus facilitating long-term treatment of prostate cancer; however, the role of estrogen in prostate cancer remains unclear. This study aimed to determine whether polygenic risk scores (PRSs) comprising combinations of genome-wide susceptibility variants influence the clinical outcomes of prostate cancer patients. The study subjects were recruited from four medical centers in Taiwan, and genome-wide genotyping data were obtained from 643 prostate cancer patients. We derived the PRS for prostate cancer (PRS-PC) and for breast cancer (PRS-BC) for each patient. The association between the PRS-PC/PRS-BC at the age of prostate cancer onset and recurrence within seven years was evaluated using a regression model adjusted for population stratification components. A higher PRS-PC was associated with an earlier onset age for prostate cancer (beta in per SD increase in PRS = -0.89, P = 0.0008). In contrast, a higher PRS-BC was associated with an older onset age for prostate cancer (beta = 0.59, P = 0.02). PRS-PC was not associated with the risk of recurrence (hazard ratio = 1.03, P = 0.67), whereas a higher PRS-BC was associated with a low recurrence risk (hazard ratio = 0.86, P = 0.03). These results indicate that the genetic predisposition to breast cancer is associated with a low risk of prostate cancer recurrence. Further studies are warranted to explore the role of breast cancer susceptibility variants and estrogen signaling in prostate cancer progression. PMID:34094689 | PMC:PMC8167673 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer

xlomafota13 shared this article with you from Inoreader Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2124-2141. eCollection 2021. ABSTRACT The development of multidrug resistance during chemotherapy is the main obstacle for epithelial ovarian cancer (EOC) treatment. Exosomal transfer of carcinogenic microRNAs (miRNAs) might strengthen chemoresistance in recipient cells. Here, we identified through microarray analysis higher miR-429 expression in multidrug-resistant SKOV3 cells and their secreted exosomes (SKOV3-EXO) than in sensitive A2780 cells and their secreted exosomes. SKOV3-derived exosomes were internalized by A2780 cells, which permitted the transfer of miR-429. Exosomal miR-429 enhanced the proliferation and drug resistance of A2780 cells by targeting calcium-sensing receptor (CASR)/STAT3 pathway in vitro and in vivo. In addition, NF-κB-p65 was predicted to bind to the miR-429 promoter region, and the inhibition of NF-κB reduced the expression of miR-429 and led to the sensitivity of EOC c ells. Consistently, A2780 cells co-incubated with SKOV3 pretreated with an NF-κB inhibitor or miR-429 antagomir showed sensitivity to cisplatin and exhibited attenuated cell proliferation. Based on our data, exosomal miR-429 functions as a primary regulator of the chemoresistance and malignant phenotypes of EOC by targeting CASR through a mechanism promoted by NF-κB and might be a therapeutic target for EOC. PMID:34094673 | PMC:PMC8167704 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Association of pretreatment body mass index with risk of head and neck cancer: a large single-center study

xlomafota13 shared this article with you from Inoreader Association of pretreatment body mass index with risk of head and neck cancer: a large single-center study Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2343-2350. eCollection 2021. ABSTRACT Smoking and alcohol exposure continue to be the dominant risk factors for the development of head and neck squamous cell carcinoma (SCCHN) worldwide. Moreover, human papillomavirus (HPV) is associated with SCCHN, particularly SCC of the oropharynx (SCCOP). Body mass index (BMI) has been reported as a possible risk factor for SCCHN, yet the data available so far about the relationship between BMI and SCCHN risk have been mixed. We sought to clarify this relationship. BMI and demographic, clinical, and epidemiological information at diagnosis were collected from 2310 SCCHN cases and 1915 controls (who were cancer-free) from October 2001 through May 2013. The odds ratios (ORs) and 95 percent confidence intervals (95% CI) were determined using the logistic regression process. Multivariable models were used to evaluate the strength of the relation between BMI and SCCHN risk. At diagnosis, 64 (2.8%) of the cases were underweight (BMI <18.5 kg/m2), 661 (28.6%) were normal weight (BMI 18.5<25 kg/m2), 833 (36.1%) were overweight (BMI 25<30 kg/m2), and 752 (32.6%) were obese (BMI ≥30 kg/m2). Comparatively, the ORs (95% CIs) for SCCHN associated with being underweight, overweight, and obese were 2.6 (1.54.7), 0.7 (0.6-0.8), and 0.8 (0.7-0.9), respectively, after adjusting for age, gender, race/ethnicity, smoking, and alcohol consumption. On analysis stratified by tumor sites, the risk of SCCOP among patients seropositive for HPVE6 and/or HPVE7 was higher among the overweight (OR, 5.4, 95% CI, 1.3-23.1) and obese patients (OR, 2.4, 95% CI, 1.1-7.6) compared to the normal weight patients. These findings suggest that pretreatment BMI could be a major risk factor for SCCHN, and the association between BMI and HPV may increase the risk of SCCOP. PMID:34094690 | PMC:PMC8167690 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.