tbuckley/cabot-search huggingface dataset:
PSA levels of &gt;1.5-4 ng/mL in a men’s health evaluation as a method for informed decision making.
Authors: E. David Crawford, Aditi Patel, Alan W. Partin, Stacy Loeb, Paul Arangua, Wendy Poage, Nelson Stone
Journal: Journal of Clinical Oncology (2015)

e16039 Background: Prostate Specific Antigen (PSA) is one of the most important tumor markers in oncology. However, its use is controversial for early detection of prostate cancer due in part to over-diagnosis and overtreatment. There is agreement among some medical organizations that the best practice is informed decision before performing a PSA blood test. Yet, this option is often difficult, impractical and time consuming. The majority of PSA tests are ordered by Family Practitioners and they have many important healthcare issues to discuss with men during annual visits. We propose that PSA be treated like other blood parameters routinely obtained in men. Only abnormal tests are discussed and Informed decision-making might then begin. Crawford et al. (BJU Int. 2011 Dec;108(11):1743-9) found that men with a PSA < 1.5 constitute a very low risk category for developing CaP within 5 years (.5%) However men with PSA ≥ 1.5 -4ng/ml have a risk of 7.9% and if African American, 10.4%. Therefore men with a PSA < 1.5ng/ml could return in 5 years while those in the > 1.5-4 zone should undergo informed decision discussion. We wanted to see in a screening population what percent of men would fit into each category. Methods: We evaluated two groups of men from the Prostate Cancer Awareness Week (PCAW) screening population. 1948 men were first time participants while 9795 men had previously participated. Using 3 cutoff parameters for PSA ( ≤ 1.5, ≤ 2.5, ≤ 4 ng/ml), we compared the two groups with a 2 proportion z test to evaluate differences in proportions between groups. Outliers (±3 SD) were removed from the sample. Results: Among first time participants as compared to previous participants, there was a significant difference in the proportion of men who had a PSA ≤ 1.5 (70% versus 65%) and ≤ 2.5 ng/ml (82% versus 80%), respectively (p = 4.44e-6, p = .0092). However, in a PSA range ≤ 4ng/ml, the proportions were not statistically significant (90% versus 91%, p = .446). Conclusions: PSA should be performed as a routine test. Men with PSA levels > 1.5 ng/mL should undergo more intensive counseling and possible evaluation. Based on our analysis, 70% of men would be directed to have a repeat PSA in 5 years while 30% would undergo this counseling, usually by an urologist.
Separation, recovery, and digital quantification of pure cell populations from tumor FNA samples using the DEPArray system.
Authors: Valeria Sero, Chiara Bolognesi, Genny Buson, Giulio Signorini, Claudio Forcato, Francesca Fontana, Stefano Gianni, Maximilian Sergio, Gianni Medoro, Nicolò Manaresi, Farideh Z Bischoff
Journal: Journal of Clinical Oncology (2015)

e22179 Background: We have previously shown reliability in isolating pure populations of (rare) cells from complex tissues using the DEPArray system. Fine Needle Aspiration (FNA) is a quick and safe procedure used to remove fluid and/or cells from a lesion or cyst to detect or confirm malignancy. Not only is FNA used to confirm cancer it’s also used to evaluate the effect of treatment. Unfortunately, FNA procedures yield very small numbers of cells, making it often difficult to detect and analyze tumor cells that are present in relatively low numbers. Here we demonstrate preliminary results showing 100% efficiency in recovery of pure tumor cell populations from FNA samples known to have low tumor burden using the DEPArray platform. Methods: Formalin fixed paraffin embedded FNA sections (n = 5; one 50 microns each) from metastases originating from pancreatic (n = 2) and breast (n = 3) primary tumors were evaluated. Each was processed using a gentle tissue disassociation and staining procedure followed by DEPArray sorting based on cytokeratin (Ker), vimentin (Vim) and nuclear staining to verify DNA content. The recovered cell populations were directly lysed in the collection tube prior to PCR-based target enrichment for next generation sequencing using IonTorrent AmpliSeq CHPv2. Results: DEPArray sorting allowed identification of 3 distinct cell populations representing tumor (KER+), stromal (VIM+) and EMT (KER+/VIM+) cells. Overall, only 2% (0.2% to 5% range) of the total (mean of 6335) cells analyzed were of tumor (KER+) origin. Groups of pure cells (mean 105 cells, range 15-200) for each population were recovered and are currently undergoing sequence analysis. Conclusions: DEPArray resolves two pressing problems associated with FNA samples obtained for genomic analysis: too few target cells and unwanted admixture of normal cells. Thus, the DEPArray platform brings precision to detection, quantification and recovery of pure target cells for subsequent downstream molecular analysis that can improve cancer diagnosis and treatment decisions.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION
Authors: Oswald H. Robertson, Richard H. P. Sia
Journal: The Journal of Experimental Medicine (1927)

A study was made of the pneumococcidal action of serum-leucocyte mixtures of pneumococcus-resistant animals with a view to determining whether this property of the blood is to be accounted for by the presence of certain serum constituents or by cellular characteristics which are lacking in the blood of susceptible animals. By means of a method specially developed for this purpose, it was found that, after adequate contact with the serum of pneumococcus-resistant animals, virulent pneumococci were phagocyted actively not only by the homologous leucocytes but also by the leucocytes of other resistant and susceptible animals. On the other hand, pneumococci exposed to the action of the serum of pneumococcus-susceptible animals were not taken up by the leucocytes of either the resistant or susceptible species. All the resistant animals tested, dog, cat, sheep, pig and horse, showed marked opsonic properties in their blood serum which were not found in the serum of susceptible ones, rabbit, guinea pig and human. There appeared, however, to be no essential difference in the phagocytic activity of the leucocytes from the various animals. It was then shown that the pneumococcus-destroying power of serum-leucocyte mixtures was entirely abolished when heated serum was substituted for fresh serum and that such heated serum had lost much of its opsonic potency. Neither the living leucocytes alone nor extracts of the leucocytes were observed to exert any killing action on pneumococci. Further evidence of the controlling influence of opsonic action in the antipneumococcus defence mechanism of the blood, and its importance in natural resistance, was afforded by a study of the opsonin content and leucocytic functions of the blood of full grown and young rabbits as related to their widely varying degrees of pneumococcus susceptibility.
The impact of race on perceptions of anxiety after radical prostatectomy.
Authors: Shilajit Kundu, Vincent Wong, David Victorson, James Burns, Sandra Guitierrez, Kevin McVary, Edward M. Schaeffer, Sarah P Psutka, Joshua Meeks, Anthony J Schaeffer, Adam Murphy, David Cella
Journal: Journal of Clinical Oncology (2017)

e538 Background: Despite the potential side effects associated with treating prostate cancer, many men choose treatment over observation. The relative treatment benefits and harms to heath related quality of life outcomes (HRQOL) remain poorly understood. In particular, there is a paucity of data detailing the differences in perceived treatment outcomes in African American (AA) and Hispanic men. We prospectively evaluated the functional and psychosocial effects of prostate cancer treatment in men and hypothesize that there may be differences in outcomes in Caucasian men vs. AA/Hispanic men. Methods: We enrolled 105 men with recently diagnosed prostate cancer at our institution in an internet-based study which used validated questionnaires to longitudinally assess HRQOL domains such as sexual and urinary function, bowel function, anxiety, and depression, at 1, 3, 6, and 12 months following treatment. Linear mixed models were used to examine changes in self-reported measures at enrollment (pre-treatment) and at each post-treatment follow-up assessment. We focused our analysis on the 62 patients who chose radical prostatectomy as treatment: 49 of these men were non-Hispanic white; 13 were AA or Hispanic. Results: Despite significant declines in functional outcomes such as erectile function (P &lt; .001 for both groups), anxiety was significantly lowered post-treatment in both groups as well. Significant reductions in anxiety were noted for Caucasian men (4.6 points , P &lt; 0.001) and were even greater for AA/Hispanic men (7.9 points, P &lt; .001). When controlling for differences in income, marital status, education, and improvements in urinary score, the impact on anxiety remained significant (P &lt; 0.05) at 3, 6, and 12 months . Based on previous analysis, these improvements are both statistically and clinically significant improvements. Conclusions: We found significant reductions in anxiety after prostate cancer surgery. While these reductions were found in all men, AA and Hispanic men reported a greater reduction in anxiety compared to the Caucasian cohort. This suggests that AA/Hispanic men may have a different perspective regarding prostate cancer and treatment outcomes. Further work is necessary to elucidate this difference in perspective.
Molecular analysis of sarcomatoid renal cell carcinoma (sRCC).
Authors: Thai Huu Ho, Sherri Z. Millis, David Bryant, Zoran Gatalica, Sandeep K. Reddy, Melissa L. Stanton, Erik P. Castle, Richard Wayne Joseph, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2015)

4556 Background: Patients with sRCC have a have a poor prognosis and decreased likelihood of response to targeted therapy or IL-2. Predictive biomarkers of response are lacking in sRCC. We evaluated a cohort of RCC patients to identify potentially actionable recurrent molecular aberrations. Methods: 112 renal cases referred to Caris Life Sciences over 2 years were evaluated for sarcomatoid components with central pathology review. 91 cases were clear cell (ccRCC) and 21 were sRCC. Testing included sequencing (next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and gene amplification (CISH or FISH). For sequencing, DNA was isolated by microdissection of the sarcomatoid component. 20 RCC cases with sarcomatoid differentiation from Mayo Clinic Arizona were analyzed for external validation. Results: The sRCC cohort showed 54% aberrant expression of PD-L1 and all but 1 case was infiltrated with PD-1+ tumor infiltrating lymphocytes (TILs). 100% of ccRCC with sarcomatoid features (n = 4) showed aberrant expression of PD-L1 and were infiltrated with PD-1+ TILs; of ccRCC without sarcomatoid features, only 17% had PD-L1 and 62% had PD-1 involvement. ccRCC had a 54% loss of PTEN, while sRCC had a 33% loss (p value = 0.2). Loss of PBRM1 expression was observed in 30% of sRCC. Loss of histone 3 lysine 36 trimethylation (H3K36me3), associated with SETD2 mutations, was observed in 19% of sRCC and 30% of ccRCC. Key differences are shown in the table below. Conclusions: Multiplatform molecular profiling of sRCC identifies numerous predictive biomarkers to cytotoxic agents and immunotherapies. In other solid tumors, overexpression of TOPO2A and loss of RRM1 are associated with sensitivity to anthracyclines and gemcitabine, respectively. sRCC have increased infiltration of PD-1+ TILs and may respond to PD1/PD-L1 targeted immunotherapies. Further evaluation of TOPO2A, RRM1 and PD-1/PD-L1 as predictive biomarkers in sRCC is warranted. % Overexpression TILs % Loss TOPO2A AR PD-L1 PD-1 RRM1 PBRM1 ccRCC 25 26 17 62 100 58 sRCC 67 5 54 96 74 30 p value 0.0001 0.04 0.005 0.003 0.0001 0.02
Retrast: Retreatment after adjuvant trastuzumab—Our regional southern Italy experience.
Authors: Michele Caruso, Vincenzo Adamo, Paolo Tralongo, Dario Giuffrida, Vittorio Gebbia, Vita Leonardi, Hector J. Soto Parra, Roberto Valenza, Nicolo Borsellino, Maria Vita Sanò, Domenico Priolo, Anna Maria Di Mari, Angela Prestifilippo, Giuseppina Ricciardi, Eleonora Miano, Alessandra Zacchia, Francesco Ferraú
Journal: Journal of Clinical Oncology (2013)

e11526 Background: Trastuzumab (T) is the standard of care for pts with HER2+ve BC. Relapse after adj T remains a rare event. Since the large use of T in adj setting, becomes crucial to evaluate advantages of retreatment with T for pts who relapsed after treatment in early stage. There is still lack of clinical evidence and poor data from CT to say that there is a benefit in T re-exposure after relapse following adj T. Methods: Since Jun 2006 and Dec 2011, we reviewed pts with early BC treated with T in adj therapy, relapsed and re-treated with T in first line therapy, in 10 departments of medical oncology in Sicily. We aimed to study feasibility, responses and treatment outcome. Results: 62 pts with HER2+ve fulfilled the criteria for this analysis and 47 were evaluated. Pts had a median age of 53 ys (29-79). ER/PgR-ve cases were 16 (34 %). Ki67 was &gt; 20% in 34 pts (74%). 31 pts (64%) had &gt;3 nodes+ve. All the pts received adj therapy with anthra+/-taxane. 55% of pts had &gt;2 metastatic sites. 12 (25,5%) pts were revalued for HER2: 10 pts confirmed 3+ and two pts 2+ were FISH+. Median time from diagnosis to relapse was 25 mos (7 – 36). Median time from last dose of T to relapse was 10 ms (2 – 35). 33 (70,2%) pts and 14 pts (29,8%) had early (&lt; 12 ms) and late progression (≥ 12 ms) respectively after adj T. First line of therapy was T in combination with mono/polychemotherapy in 42 pts (89,3%) and 5 pts (10,6%) respectively. 27 pts (57,4%) had objective responses (CR 5, PR 22) and 7 pts (14,8%) stable disease. 13 pts (27,6%) had progression: all of these pts had early progressive disease after adj T, 9 pts (69,2%) had Ki67&gt;20%, 5 pts (38,4%) were ER/PgR-ve and 8 pts (61,5%) ER/PgR+ve. Median TTP was 4 mos (range 2-7). Median TTP for early and late relapses pts were respectively 3,7 and 4,8 mos, (p = 0,4). Median OS from relapse to death was 23 mos (r 12 – 37). LVSD G1 (EF &lt; 60-50%) was observed only in 7 pts (14%). Conclusions: Our data confirm the feasibility and safety of treatment with T after adj T therapy and is active for a disease control rate in 72,4% of cases. These results demonstrate that relapses after adj T occurred early (&lt;12 ms) in 70% of pts. However pts with primary resistance (27,6%) should be well categorized using biomolecular markers to receive up-front drugs that overcome the resistance to T.
Generic drugs have lost their profitability
Authors: Cornelis A van den Bogert
Journal: BMJ (2017)

Meeran and colleagues argue that1 Actavis charging around £100 (€116; $125) for a month’s supply of hydrocortisone in the UK is scandalous, compared with its price in Spain (£3.12 a month). I question whether the price of highly effective corticosteroid therapy is …
ARH460–16-2: a therapeutic monoclonal antibody targeting CD44 in Her2/neu negative breast cancer
Authors: D. S. Young, D. Sayegh, J. Desousa-Hitzler, S. E. Hahn
Journal: Journal of Clinical Oncology (2004)

2622 Background: ARH460–16-2 is a potent anti-CD44 antibody that has been shown to suppress and delay tumor growth and increase survival in a xenograft model of Her2/neu-negative breast cancer. CD44, a cancer-related membrane glycoprotein, is believed to play a critical role in cellular adhesion, migration, invasion and tumorigenicity. Current results describe the prevalence of this epitope in a survey of cancer tissues. Methods: Distribution of the ARH460–16-2 CD44 epitope in breast cancer was determined by the immunohistochemistry of breast cancer sections from 50 individual patients in an array format. Prevalence of the antigen in a range of human cancers was determined by immunohistochemistry of multiple tumors in an array format. Samples were scored according staining intensity, tissue specificity, cellular localization, and section score. Results: Overall, 62% of breast cancer patient samples tested were positive for ARH460–16-2 antigen, while only 4/10 normal breast tissue samples from those patients were positive. Expression of ARH460–16-2 within patient samples appeared specific for cancer cells as staining was restricted to malignant cells. There was no correlation of the ARH460–16-2 binding to the estrogen or progesterone receptor status of the patient. 62% of the sections that were negative for Her2/neu were positive for ARH460–16-2. 23% of sections expressed both the ARH460–16-2 antigen and Her2/neu, suggesting potential for additive therapeutic effects through independent mechanisms of action. To examine the potential therapeutic benefits of ARH460–16-2, the frequency and localization of the antigen within various human cancer tissues was determined. The majority of tumor types including skin, lung, liver, stomach and kidney, in addition to breast cancer, expressed the ARH460–16-2 antigen. Conclusions: CD44, the antigen recognized by the therapeutic antibody ARH460–16-2, is widely distributed in human cancers. In particular, this epitope is present in samples from breast cancer patients that are negative for Her2/neu, and thus may be a target for antibody therapy to provide options for this group of breast cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ARIUS Research, Inc. ARIUS Research, Inc. ARIUS Research, Inc.
Using gamma-H2AX and H2AX quantitative ELISA for monitoring DNA damage induced by chemotherapeutic agents and irradiation exposure.
Authors: Jiuping Jay Ji, Yiping Zhang, Christophe E. Redon, Alice Chen, Susan Holbeck, Melinda G. Hollingshead, Ralph E. Parchment, Yves Pommier, Joseph E. Tomaszewski, James H. Doroshow, William Bonner
Journal: Journal of Clinical Oncology (2015)

2559 Background: Gamma-H2AX (γH2AX) is a biomarker for DNA double-strand breaks and programmed cell death, but variable relative amounts of H2AX in different samples causes ambiguity in the meaning of the γH2AX level unless it is related to total H2AX levels. We developed a 96-well plate-based ELISA for quantifying γH2AX and H2AX levels in crude extracts of tumor cells, CTCs and biopsy tissues and are validating it for applications in irradiation exposure monitoring and in pharmacodynamic evaluation of anti-cancer agents. Methods: The ELISA was used to analyze extracts of several NCI60 tumor cell lines that had been exposed to a variety of agents, including ionizing radiation, inhibitors of Top-1 (CPT, SN-38, Topotecan), PARP (ABT-888, AZD-2281, MK-4827) and ATR (VE-821, VE-822, AZD-6738, Compound 45, NU-6027), and their combinations. Combination regimens of CPT-11 with PARP inhibitors (ABT-888, AZD-2281, MK-4827) were further evaluated in vivo in the A375 xenograft mouse model. Patient samples obtained for research purposes were also examined by ELISA for feasibility and utility. Results: In vitro, dose-dependent increases in the ratio of γH2AX to H2AX were detected after escalating ionizing radiation exposure and concentration-dependent increases after Top-1 exposure. Treating with inhibitors of PARP or ATR alone did not significantly induce γH2AX. Combinations of Top-1 inhibitors with PARP or ATR inhibitors led to synergistic induction of DNA damage. Among five ATR inhibitors evaluated in combination with Top-1 inhibitors, VE-822 and AZD-6738 were observed to have the highest synergy for γH2AX induction, while NU-6027 showed none. Combinations of CPT-11 with ABT-888, AZD-2281 or MK-4827 showed synergistic induction of γH2AX in A375 xenografts in vivo. Additional testing of human specimens including PBMCs, bone marrow and tumor biopsies proved the assay's clinical suitability and potential advantages. Conclusions: A newly developed quantitative ELISA for measuring both γH2AX and H2AX is ready for clinical validation for monitoring DNA damage induced by chemotherapeutic agents or irradiation exposure. Funded by NCI Contract No. HHSN261200800001E.
The clinical effects of hepatic artery infusion of recombinant adenoviral human p53 gene combined with local chemo- and radiotherapy in treatment of advanced hematocarcinoma.
Authors: Shaowen Xiao, Jianhao Geng, Shanwen Zhang
Journal: Journal of Clinical Oncology (2013)

e15166 Background: Advanced are generally resistant to both chemo- and radio-therapy. P53 gene has multiple anti-cancer functions including sensitizing tumor cells to chemo- and radio-therapy. Methods: Twenty-two patients with an age of 51.5±19.0 years old, 15 males and 7 females, 21 in stage IV and 1 in stage III, were treated with combination of p53 gene, chemo- and radio-therapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through hepatic artery pump at a dose of 2 x 10 12 viral particles once per week for 4-9 times. The chemo-regimen consisting of doxorubicin 20mg/m 2 and Oxaliplatin 40mg/m 2 were administered through the same pump once a week for 4-8 times. Intensity modulated radiation therapy were given at a total dose of 20 – 60 Gy in 4 weeks. Results: The overall response rate at 3 months after treatment was 31.7% (7/22, 1/22 in CR and 6/22 in PR). Thirteen patients (59.1%) were stable. Medium overall survival and progress free survival time were 11 and 5.5 months, respectively. The survival rates of one year, two years and three years were 31.8%, 13.6%, and 4.5%, respectively. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene, chemo- and radio-therapy is effective and safe treatment regimen for advanced hepatocarcinoma.