Distinct Mutational Landscape of Inverted Urothelial Papilloma

A recent study has identified gene mutations involving the MAPK/ERK pathway, particularly the HRAS gene, in all inverted urothelial papillomas (IUPs), in the absence of pathway mutations in TERT promoter, FGFR3, and TP53/RB1genes. Neither recurrence nor progression was observed in IUPs. These data support several longstanding hypotheses: (1) IUPs are benign and do not recur or progress; (2) they harbor mutations that are different from those of urothelial carcinoma; and (3) they arise through different molecular mechanisms than low‐ or high‐grade urothelial carcinoma. As the most critical differential diagnosis in this context is inverted‐type urothelial carcinoma, more comprehensive studies are needed to compare and contrast these entities

Differential gene expression between African American and Caucasian American prostate cancer

Background: African-American (AA) men have higher incidence and mortality from prostate cancer compared to Caucasian-American (CA) men. Increasing evidence suggests that genetic and molecular alterations play important roles. We identified a 5 gene panel viz. p-Akt (Ser473), chemokine (C-X-C motif) receptor 4 (CXCR4), fatty acid synthase (FASN), interleukin-6 (IL-6) and matrix metallopeptidase 9 (MMP-9) highly expressed in prostate cancer and analyzed their expression in AA and CA cohorts. Methods: IHC of p-Akt, CXCR4, FASN, IL-6 and MMP-9 were evaluated in RRP specimens (n=20) from each ethnic group exhibiting Gleason scores ranging from 6 through 9. Results: Low to medium staining for p-Akt and weak focal staining for MMP-9 was observed in the cytoplasm of tumor cells (10-20%) in80% of tumor cells in both groups. Expression of IL-6 varied from weak to moderate intensity between (20-100% tumor cells) in 85% cases in CA- and 75% in AA- specimens. A marked difference in CXCR4 expression was noted between AA- and CA- cancer specimens. Weak CXCR4 staining was noted85% of AA- prostate cancer exhibited weak to strong CXCR4 expression in between 10-100% of tumor cells localized in membrane, cytoplasm and nucleus in high-grade tumors. Conclusions: CXCR4 expression appears to be distinctly different in prostate cancers from AA and CA men. Further studies are needed to assess whether this distinction correlates with prognosis between racial groups

Maspin Expression and its Metastasis Suppressing Function in Prostate Cancer

Mammary Serine Protease Inhibitor (Maspin) is a unique member of the serpin family with tumor suppressive properties. Maspin is a secreted protein encoded by a class II tumor suppressor gene, expressed in normal prostate luminal and basal cells but reduced or absent in prostate cancer. Currently, there is a consensus that maspin expression in prostate cancer is an indicator of a better prognosis and is a predictive marker for therapeutic response in prostate cancer. Experimental evidence consistently indicates that maspin suppresses tumor growth, invasion, and metastasis and promotes apoptosis in cancer cells. In this chapter, we discuss regulation of maspin expression, binding partners of maspin, and pathways through which maspin exerts its tumor suppressive properties. In addition, we summarize the progress that investigators have made in clarifying the role of maspin in prostate cancer biology and in assessing its role as a diagnostic marker and therapeutic agent

Mitoxantrone is superior to doxorubicin in a multiagent weekly regimen for patients older than 60 with high-grade lymphoma: results of a BNLI randomized trial of PAdriaCEBO versus PMitCEBO

A prospective, multicenter, randomized trial was undertaken to compare the efficacy and toxicity of adriamycin with mitoxantrone within a 6-drug combination chemotherapy regimen for elderly patients (older than 60 years) with high-grade non-Hodgkin lymphoma (HGL) given for a minimum of 8 weeks. A total of 516 previously untreated patients aged older than 60 years were randomized to receive 1 of 2 anthracycline-containing regimens: adriamycin, 35 mg/m2 intravenously (IV) on day 1 (n = 259), or mitoxantrone, 7 mg/m2 IV on day 1 (n = 257); with prednisolone, 50 mg orally on days 1 to 14; cyclophosphamide, 300 mg/m2 IV on day 1; etoposide, 150 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 8; and bleomycin, 10 mg/m2 IV on day 8. Each 2-week cycle was administered for a minimum of 8 weeks in the absence of progression. Forty-three patients were ineligible for analysis. The overall and complete remission rates were 78% and 60% for patients receiving PMitCEBO and 69% and 52% for patients receiving PAdriaCEBO (P = .05, P = .12, respectively). Overall survival was significantly better with PMitCEBO than PAdriaCEBO (P = .0067). However, relapse-free survival was not significantly different (P = .16). At 4 years, 28% of PAdriaCEBO patients and 50% of PMitCEBO patients were alive (P = .0001). Ann Arbor stage III/IV, World Health Organization performance status 2-4, and elevated lactate dehydrogenase negatively influenced overall survival from diagnosis. In conclusion, the PMitCEBO 8-week combination chemotherapy regimen offers high response rates, durable remissions, and acceptable toxicity in elderly patients with HGL

Molecular testing for BRAF mutations to inform melanoma treatment decisions: a move toward precision medicine

Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor.' These results were filtered to include manuscripts that focused on diagnostic tests for determining BRAF mutation status. Numerous BRAF testing methods were identified, including DNA-based companion diagnostic tests and DNA- and protein-based laboratory-developed tests. Herein we review the characteristics of each method and highlight the strengths and weaknesses that should be considered before use and when interpreting results for each patient. Molecular profiling has shown that mutation load increases with melanoma tumor progression and that unique patterns of genetic changes and evolutionary trajectories for different melanoma subtypes can occur. Discordance in the BRAF mutational status between primary and metastatic lesions, as well as intratumoral heterogeneity, is known to occur. Additionally, the development of acquired resistance to combination BRAF and MEK inhibitor therapy is still a formidable obstacle. Therefore, tumor heterogeneity and the development of acquired resistance have important implications for molecular testing and ultimately the treatment of patients with advanced-stage melanoma. Overall, this information may help community oncologists more accurately and effectively interpret results of diagnostic tests within the context of recent data characterizing melanoma tumor progression

Evaluating the typical day-to-day variability of WHOOP-derived heart rate variability in Olympic water polo athletes

Heart rate (HR) and HR variability (HRV) can be used to infer readiness to perform exercise in athletic populations. Advancements in the photoplethysmography technology of wearable devices such as WHOOP allow for the frequent and convenient measurement of HR and HRV, and therefore enhanced application in athletes. However, it is important that the reliability of such technology is acceptable prior to its application in practical settings. Eleven elite male water polo players (age 28.8 ± 5.3 years [mean ± standard deviation]; height 190.3 ± 3.8 cm; body mass 95.0 ± 6.9 kg; international matches 117.9 ± 92.1) collected their HR and HRV daily via a WHOOP strap (WHOOP 3.0, CB Rank, Boston, MA, USA) over 16 weeks ahead of the 2021 Tokyo Olympic Games. The WHOOP strap quantified HR and HRV via wrist-based photoplethysmography during overnight sleep periods. The weekly (i.e., 7-day) coefficient of variation in lnRMSSD (lnRMSSDCV) and HR (HRCV) was calculated as a measure of day-to-day variability in lnRMSSD and HR, and presented as a mean of the entire recording period. The mean weekly lnRMSSDCV and HRCV over the 16-week period was 5.4 ± 0.7% (mean ± 95% confidence intervals) and 7.6 ± 1.3%, respectively. The day-to-day variability in WHOOP-derived lnRMSSD and HR is within or below the range of day-to-day variability in alternative lnRMSSD (~3–13%) and HR (~10–11%) assessment protocols, indicating that the assessment of HR and HRV by WHOOP does not introduce any more variability than that which is naturally present in these variables

Differentially Expressed Genes and Molecular Pathways in an Autochthonous Mouse Prostate Cancer Model

Prostate cancer remains a major public health problem and the second leading cause of cancer-related deaths in men in the United States. The present study aims to understand the molecular pathway(s) of prostate cancer which is essential for early detection and treatment. Dorsolateral prostate from 20 week transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, which spontaneously develops prostate cancer and recapitulates human disease and age-matched non-transgenic littermates were utilized for microarray analysis. Mouse genome network and pathway analyses were mapped to the human genome using the Ingenuity Pathway Analysis (IPA) database for annotation, visualization, and integrated discovery. In total, 136 differentially expressed genes, including 32 downregulated genes and 104 upregulated genes were identified in the dorsolateral prostate of TRAMP, compared to non-transgenic mice. A subset of differentially expressed genes were validated by qRT-PCR. Alignment with human genome database identified 18 different classes of proteins, among these, 36% were connected to the nucleic acid binding, including ribosomal proteins, which play important role in protein synthesis—the most enriched pathway in the development of prostate cancer. Furthermore, the results suggest deregulation of signaling molecules (9%) and enzyme modulators (8%) affect various pathways. An imbalance in other protein classes, including transporter proteins (7%), hydrolases (6%), oxidoreductases, and cytoskeleton proteins (5%), contribute to cancer progression. Our study evaluated the underlying pathways and its connection to human prostate cancer, which may further help assess the risk of disease development and progression and identify potential targets for therapeutic intervention

FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: incidence and etiological considerations

n/

TMPRSS2â ERG gene fusion is rare compared to PTEN deletions in stage T1a prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136332/1/mc22535.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136332/2/mc22535_am.pd

ChlVPP alternating with PABlOE is superior to PABlOE alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation/Central Lymphoma Group randomized controlled trial

The purpose of this randomized trial was to compare the efficacy of 6 cycles of prednisolone, Adriamycin (doxorubicin), bleomycin, vincristine (Oncovin) and etoposide (PABlOE) with 3 cycles of PABIOE that alternate with 3 cycles of chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) in patients with advanced Hodgkin's disease. Between October 1992 and April 1996, 679 patients were entered onto the study. 41 of these did not match the protocol requirements on review and were excluded from further analysis, most of these being reclassified as NHL on histological review. Of the remaining 638 patients, 319 were allocated to receive PABIOE and 319 were allocated to receive ChlVPP/PABlOE. The complete remission (CR) rates were 78% and 64%, for ChlVPP/PABlOE and PABIOE respectively after initial chemotherapy (P< 0.0001). 124 patients were re-evaluated subsequently following radiotherapy to residual masses. The CR rates changed from 78% to 88% for ChlVPP/PABlOE and from 64% to 77% for PABlOE when re-evaluated in this manner (treatment difference still significant P = 0.0002). The treatment associated mortality in the PABlOE arm was 2.2% (7 deaths), while there were no such deaths in the ChlVPP/PABlOE arm (P = 0.015). The failure-free survival was significantly greater in the ChlVPP/PABlOE arm (P< 0.0001) as was the overall survival (P = 0.01). The failure-free and overall survival rates at 3 years were 77% and 91% in the ChlVPP/PABlOE arm, compared with 58% and 85% in the PABIOE arm, respectively. These results indicate that ChlVPP alternating with PABIOE is superior to PABIOE alone as initial treatment for advanced Hodgkin's disease.© 2001 Cancer Research Campaign www.bjcancer.co