Endothelin Signaling as Target for Anticancer Therapy: from Prostate Cancer to Multiple Myeloma

2018 ◽  
Vol 2 (1) ◽  
pp. 1-3
Author(s):  
Panagiotis J. Vlachostergios ◽  
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Anticancer Therapy

scholarly journals Self-reported causes of cancer among 6881 survivors with 6 tumour types: results from the PROFILES registry

2021 ◽  
Author(s):  
Carla Vlooswijk ◽  
Olga Husson ◽  
Simone Oerlemans ◽  
Nicole Ezendam ◽  
Dounya Schoormans ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Cancer Survivors ◽  
Causal Attributions ◽  
Population Based ◽  
Comorbid Conditions ◽  
Prostate Cancer Survivors ◽  
Cancer Types ◽  
External Causes ◽  
Single Question

Abstract Objective Our aim was to describe and compare self-reported causal attributions (interpretations of what caused an illness) among cancer survivors and to assess which sociodemographic and clinical characteristics are associated with them. Methods Data from five population-based PROFILES registry samples (i.e. lymphoma (n = 993), multiple myeloma (n = 156), colorectal (n = 3989), thyroid (n = 306), endometrial (n = 741), prostate cancer (n = 696)) were used. Causal attributions were assessed with a single question. Results The five most often reported causal attributions combined were unknown (21%), lifestyle (19%), biological (16%), other (14%), and stress (12%). Lymphoma (49%), multiple myeloma (64%), thyroid (55%), and prostate (64%) cancer patients mentioned fixed causes far more often than modifiable or modifiable/fixed. Colorectal (33%, 34%, and 33%) and endometrial (38%, 32%, and 30%) cancer survivors mentioned causes that were fixed, modifiable, or both almost equally often. Colorectal, endometrial, and prostate cancer survivors reported internal causes most often, whereas multiple myeloma survivors more often reported external causes, while lymphoma and thyroid cancer survivors had almost similar rates of internal and external causes. Females, those older, those treated with hormonal therapy, and those diagnosed with prostate cancer were less likely to identify modifiable causes while those diagnosed with stage 2, singles, with ≥2 comorbid conditions, and those with endometrial cancer were more likely to identify modifiable causes. Conclusion In conclusion, this study showed that patients report both internal and external causes of their illness and both fixed and modifiable causes. This differsbetween the various cancer types. Implications for Cancer Survivors Although the exact cause of cancer in individual patients is often unknown, having a well-informed perception of the modifiable causes of one’s cancer is valuable since it can possibly help survivors with making behavioural adjustments in cases where this is necessary or possible.

Safety and Pain Palliation of Zoledronic Acid in Patients with Breast Cancer, Prostate Cancer, or Multiple Myeloma Who Previously Received Bisphosphonate Therapy

2004 ◽  
Vol 9 (6) ◽  
pp. 687-695 ◽  
Author(s):  
Charles L. Vogel ◽  
Ronald H. Yanagihara ◽  
Albert J. Wood ◽  
Frederick M. Schnell ◽  
Charles Henderson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Zoledronic Acid ◽  
Bisphosphonate Therapy ◽  
Pain Palliation ◽  
Cancer Prostate

Chromosome 1q Amplification Is Associated with a History of Prior Malignancies Among Patients Newly Diagnosed with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2193-2193
Author(s):  
Elizabeth B Lamont ◽  
Andrew J. Yee ◽  
Stuart L. Goldberg ◽  
Andrew D Norden
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Usual Care ◽  
Real World ◽  
Research Funding ◽  
Newly Diagnosed ◽  
History Of ◽  
Equity Ownership ◽  
Prior Malignancy

Background: Over the past 20 years, observational data from usual care clinical oncology settings has been leveraged to inform estimates of cancer treatment-associated benefits and risks among patients not treated on clinical trials. Increasing genomic testing to inform treatment decisions in usual care settings now meaningfully augments traditional observational data, positioning it to provide insights beyond clinical care into tumor biology. We studied patients with newly diagnosed multiple myeloma (MM), comparing cytogenetic test patterns according to history of prior malignancy. Methods: In this retrospective cohort study, we identified 2,380 patients from the COTA real-world database (RWD) who were newly diagnosed with MM in the years 2010-2018. The COTA RWD is a de-identified composite of both abstracted electronic health record and administrative data pertaining to patients receiving their cancer care at one of COTA's clinical oncology practice partners. Among these patients, 1769 (74%) had evidence of MM-associated cytogenetic testing with fluorescent in-situ hybridization (FISH) within the 120 days surrounding their date of diagnosis. The 1,769 patients form the analytic cohort. We compared patients' FISH results for t(4;14), deletion(17p), t(14;16), deletion(13), t(14;20), t(6;14), t(11;14), deletion (1p), and amplification(1q) according to their history of prior malignancy. Results: Within the cohort, 263 prior malignancies were identified in 241 patients (14%, 241/1,769). Two-hundred and twenty-one patients (92%) had one prior malignancy, 28 (7.9%) had two prior malignancies, and one (<1%) had four prior malignancies. The most common prior malignancies were prostate (n=50), breast (n=19), melanoma (n=14), skin (n=13), and cervix (n=6). Amplification of the long arm of chromosome one (amp(1q)) was noted in 31% of patients (75/241) with a prior malignancy vs. 24% of patients (370/1,528) without (chi2 test p=0.02). Overall 25% of patients had amp(1q). No other translocations, amplifications, deletions were associated with prior cancers. A non-parametric test for trend revealed a strong positive association between patients' malignancy count (range 0-4) and amp1q (p<0.01). MM patients with prior lymphomas and prior melanomas also had high rates of amp(1q), though these were not significantly different from patients without these prior malignancies. In a multivariable logistic regression model that adjusted for patient demographic attributes, other known potentially collinear MM poor prognostic factors (i.e., revised ISS stage, IgA sub-type, lambda light chains) and adjusted standard errors for clustering of patients within treatment settings, a history of prostate cancer remained clinically and statistically significantly positively associated with amp(1q) (OR 2.1, 95% CI: 1.9-2.2) as did history of two or more prior malignancies (OR 2.8, 95% CI: 2.3-3.3). Of note, amp(1q) was positively associated with IgA subtype (OR 1.5, 95% CI: 1.3-1.6) and the presence of lambda subtype (OR 1.3, 95%CI: 1.3-1.4). Conclusions: Using RWD, we found that newly diagnosed MM patients with histories of prostate cancer and those with two or more prior malignancies were more likely to have amp(1q), a poor prognostic marker in MM. Gains in 1q have previously been identified among patients with prostate and lymphoid cancers, but to our knowledge this is the first study to identify an association with a prior history of cancer, especially prostate cancer, and amp(1q) in MM. This relationship is worth further exploration of whether there is a common pathway associated with for example risk of prostate cancer and amp(1q) in MM. Clinical trials are less likely to answer this question as patients with prior malignancies are often excluded from enrollment. Overall, the results reported suggest that RWD is an efficient and comparatively inexpensive tool to support research in cancer biology through hypothesis generating and testing analyses of linked real-world phenotypic and genotypic data. Disclosures Lamont: COTA: Employment. Yee:Celgene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy; Adaptive: Consultancy; Amgen: Consultancy, Honoraria. Goldberg:Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; COTA: Equity Ownership; Bristol-Myers Squibb: Consultancy. Norden:COTA: Employment, Equity Ownership.

Patterns and determinants of chemotherapy-associated Clostridium difficile infection among cancer patients in the United States: A population-based study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19111-e19111
Author(s):  
Pramit Nadpara
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Clostridium Difficile ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Clostridium Difficile Infection ◽  
The United States ◽  
Chemotherapeutic Agents

e19111 Background: Elderly cancer patients comprise a population that is vulnerable for Clostridium difficile infection (CDI). In addition to the frequent hospitalizations, the administration of chemotherapeutic agents has been associated with the development of CDI. The objective of this study was to identify the patterns and determinants of chemotherapy-associated CDI (Chemo-CDI), in a nationwide sample of elderly patients. Methods: We used NCI’s Surveillance, Epidemiology, and End Results registry linked Medicare (SEER-Medicare) 2007-2012 files. We included patients’ aged ≥65 year, with diagnosis of lung/breast/ovarian/colorectal/prostate cancer, or lymphoma/multiple myeloma/leukemia during 2008-2011. We excluded those not receiving chemotherapy, with non-continuous Medicare enrollment, or HMO enrollment. Chemotherapy receipt was identified using appropriate ICD-9/HCPCS/CPT codes. Incidence of CDI following chemotherapy were determined by identifying any claim with primary/secondary diagnosis of CDI during the two-month follow-up period. Recurrent Chemo-CDI was identified by presence of any claim that was > 2 weeks and ≤8 weeks from the index CDI diagnosis date. Covariates including antibodies/proton pump inhibitors usage were captured and included in the analysis. Chi-square tests, and hierarchical generalized logistic models were conducted to identify determinants of Chemo-CDI. Results: We identified 41,470 elderly patients with lung/breast/ovarian/colorectal/prostate cancer, or lymphoma/multiple myeloma/leukemia diagnosis during the study years. While few (266) patients developed Chemo-CDI within one year of diagnosis, more than 50% (136) of those patients developed recurrent Chemo-CDI. Patient characteristics were not associated with risk of developing Chemo-CDI, however, significant differences were observed in antibiotics/proton pump inhibitors exposure across all cancer types (p < 0.001). Treatment for Chemo-CDI mostly comprised of Metronidazole and oral Vancomycin. Conclusions: While the incidence of Chemo-CDI is lower among patients receiving chemotherapy, the rate of recurrent Chemo-CDI was significantly higher. Strategies to prevent CDI recurrence in this population are therefore warranted. Future studies should also explore the association between increased disease burden and comorbidity, and the risk of developing Chemo-CDI.

scholarly journals Annexin II Interactions with the Annexin II Receptor Enhance Multiple Myeloma Cell Adhesion and Growth In the Bone Marrow Microenvironment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 130-130 ◽  
Author(s):  
Sonia D'Souza ◽  
Noriyoshi Kurihara ◽  
Yusuke Shiozawa ◽  
Russell Taichman ◽  
Deborah Galson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Stromal Cells ◽  
Prostate Cancer Cell ◽  
Annexin Ii ◽  
Wild Type ◽  
Prostate Cancer Cells ◽  
Akt Phosphorylation

Abstract Abstract 130 Multiple myeloma (MM) is an incurable B-cell malignancy that develops in the bone marrow. The marrow microenvironment plays a critical role in supporting homing, lodging, and growth of MM cells by activating signaling pathways in both MM and bone marrow stromal cells (BMSC). Recently, we identified that annexin II (AXII) is involved in prostate cancer cell lodgment to the bone marrow as well as mobilization of prostate cancer cells to the peripheral blood. AXII expressed on stromal cells supports prostate cancer cell lodgment via the annexin II receptor (AXIIR) on prostate cancer cells. We hypothesized that MM cells use a similar mechanism to lodge and grow in the bone marrow. We demonstrated using bio-AXII, that MM cell lines and primary MM cells from 8 MM patients express the AXIIR protein. In addition, MM cells adhered significantly better to BMSC from wild-type mice than from AXII−/− mice. Knockdown of AXIIR by siRNA in MM.1S and ANBL.6 MM cells resulted in decreased AXII binding and decreased adherence of MM cells to KM101 stromal cells and BMSC from wild-type mice. Furthermore, the adhesion of MM.1SsiCon and MM.1SsiAXIIR cells to AXII−/− BMSC was similar indicating that AXII produced by MM cells does not act in an autocrine manner on attachment. Therefore, our studies indicate the importance of the interaction of AXII on BMSC with AXIIR on MM cells in adhesion. Our studies also revealed a role for AXIIR signaling on MM cell growth. We found that soluble AXII was released by osteoclasts into their conditioned media and stimulated the growth of MM cells via ERK1/2 and AKT phosphorylation in MM cells. AXII stimulation of MM cell growth was blocked by AXII antibody or by blocking ERK1/2 and AKT phosphorylation. In contrast, endogenous AXII produced by MM.1S cells did not stimulate MM.1S cell growth suggesting that autocrine AXII/AXIIR signaling in MM.1S cells does not contribute to MM.1S cell growth. Taken together, these results suggest that AXII/AXIIR axis in the myeloma microenvironment plays an important role in MM cell adhesion and growth through production of AXII by BMSC and osteoclasts. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2121 ◽  
Author(s):  
Anmi Jose ◽  
Gautham G. Shenoy ◽  
Gabriel Sunil Rodrigues ◽  
Naveena A. N. Kumar ◽  
Murali Munisamy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Research ◽  
Molecular Docking ◽  
Clinical Practice ◽  
Cancer Therapy ◽  
Catalytic Domain ◽  
Anticancer Therapy ◽  
Docking Studies ◽  
Histone Demethylase ◽  
Lysine Specific Demethylase

Lysine-specific demethylase 5B (KDM5B/PLU1/JARID1B) is found to be overexpressed in numerous malignancies, including breast, lung, skin, liver, and prostate cancer. Identification of molecules targeting the KDM5B enzyme could be a potential lead in cancer research. Although many KDM5B inhibitors with promising outcomes have been developed so far, its further application in clinical practice is limited due to toxicity and lack of target specificity. Here, we summarize the significance of targeting KDM5B in anticancer therapy and report the molecular docking studies of some known anti-viral agents, decitabine, entecavir, abacavir, penciclovir, and 3-deazaneplanocin A in the catalytic domain JmjC of KDM5B. These studies show the repurposing potential of identified anti-viral agents in cancer therapy.

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