tbuckley/cabot-search huggingface dataset:
Cardiovascular disease (CVD) risk factors among cisplatin-treated testicular cancer survivors (TCS): A multicenter clinical study of U.S. and Canadian patients.
Authors: Chunkit Fung, Darren Richard Feldman, Robert James Hamilton, Somer Case-Eads, David J. Vaughn, Clair Beard, Malcolm J. Moore, Deepak M. Sahasrabudhe, Mary J. Brames, Sophie D. Fossa, Howard D. Sesso, Lawrence H. Einhorn, Lois B. Travis
Journal: Journal of Clinical Oncology (2015)

391 Background: The remarkable success of cisplatin-based chemotherapy in curing metastatic TC has been accompanied by potential life-threatening sequelae, including CVD. Most prior studies, however, have been conducted in Europe and included older chemotherapy regimens. We examined CVD risk factors in an ongoing multi-center clinical study of TCS given modern cisplatin-based chemotherapy (CHEM) at centers in North America (NCI 1R01 CA157823-02). Methods: TCS aged ≤49 years at time of first-line CHEM were eligible to undergo clinical examination and complete a questionnaire regarding co-morbidities, lifestyle behaviors, and prescription drug use. Results: We evaluated the first 443 consecutively enrolled TCS (23% seminoma; 77% nonseminoma) with most having stage II (52%) or III (28%) disease. The median age at time of TC diagnosis was 32 years (range 15-49 years) and median time since completion of chemotherapy was 59 months (range 1-24 years). Patients were largely white (90%), married (62%), and had full-time employment (82%) and health insurance (88%). 8% of TCS were current smokers. 48% of TCS had gained &gt;10 lbs after CHEM with 29% having a ≥102 cm (40 inch) waist circumference, and 43% and 31% having a body mass index of 25 to &lt;30 kg/m2 (overweight) and ≥ 30 kg/m 2 (obese), respectively. A sizable proportion of men had abnormal systolic (21% with 130-139 mm Hg and 17% with ≥140 mm Hg) and diastolic (35% with 80-89 mm Hg and 13% with ≥90 mm Hg) blood pressure. 14%, 11%, and 5% TCS indicated that they currently used medications for hypertension, cholesterol and diabetes, respectively. Cardiac conditions were reported by 32 TCS (7%), including angina (N=2), angioplasty/stent placement (N=1), myocardial infarction (N=1), transient ischemic attack (N=1), stroke (N=2), peripheral vascular disease (N=12), deep vein thrombosis (N=23), and pulmonary embolism (N=15). Conclusions: A number ofCVD risk factors are present in a contemporary North American cohort of TCS after CHEM. Future analytic studies should focus on mechanistic investigations to facilitate the development of screening and preventive efforts for CVD in high-risk patients.
Comparative retrospective study between best supportive care (BSC) versus chemotherapy for elderly patients with NSCLC
Authors: A. V. Katz, M. T. Arruda, J. Y. Yamaguchi, J. E. M. Rangel, C. M. Almeida, J. R. Pereira
Journal: Journal of Clinical Oncology (2004)

7355 Background: Lung cancer is a common disease in elderly patients. However, age alone is a very uncertain prognostic criteria for outcome and tolerance to treatment. Despite some meta-analysis have shown that performance status is a better criteria for treatment decision, elderly patients were poorly represented. Methods: We analyzed data from 82 patients aged 80 or older with NSCLC admitted at our institution from august 1998 to july 2003. Thirty-eight patients (46,3%) received any chemotherapy regimen. Results: Average age was 82 years. Most patients (73,2%) were men, 90.2% were ECOG PS 2 or less, 67 patients (81.7%) were clinical stage IIIB or IV and the most common histologic type was squamous-cell carcinoma. Median survival for all patients was 13.4 weeks. Patients that received chemotherapy had a significantly longer median survival compared to those that did not, 28.3 versus 8 weeks, respectively. Thirty patients (79%) from the chemo treated group received Carboplatin AUC 4 day 1 plus Vinorelbine 25 mg/m2 days 1 and 15. Twenty-eight patients from the carboplatina /vinorelbine group were evaluated for response rates, achieving an overall response of 66,6%. Conclusions: In this retrospective analysis, we concluded that even extremely old patients could get benefit with chemotherapy if their performance status permit. No significant financial relationships to disclose.
Cancer Mortality in Relatives of Retinoblastoma Patients2
Authors: Louise C. Strong, Jay Herson, Cathryn Haas, Karen Elder, Ranajit Chakraborty, Kenneth M. Weiss, Partha Majumder
Journal: JNCI Journal of the National Cancer Institute (1984)

The risk of other cancers in relatives of retinoblastoma (RTB) patients was determined by a survey of the mortality experience of siblings, parents, parental siblings, and grandparents of all U.S. or Canadian RTB patients referred to The University of Texas M. D. Anderson Hospital and Tumor Institute between 1944 and 1980. Expected mortality was ascertained by the application of age-, sex-, race-, and calendar year-specific U.S. mortality rates to the observed person-years. Among 607 relatives of 33 unilateral-sporadic RTB probands, no excess in cancer deaths was observed (observed/expected= 18/22). Among 733 relatives of 47 bilateral-familial RTB probands, a slight excess in cancer deaths was observed (41/31). A significant excess in cancer deaths occurred in relatives under age 55 years (18/9) and in fathers (7/1) of the bilateral RTB probands. To determine whether the cancer excess was related to some unique allele associated with second tumors in RTB survivors, the cancer mortality of 203 relatives of the 14 RTB patients with second tumors was examined, and no excess was observed (11/11). To determine whether the excess might be attributable to an unexpressed RTB gene or precursor, the mortality experience was examined in 6 kindreds in which parents, unaffected by RTB, had more than 1 child with RTB. Among these 72 relatives a significant excess in cancer deaths was observed (8/2). The findings demonstrate a modest overall cancer excess in relatives of hereditary RTB patients and suggest it may be attributable to an unexpressed RTB gene or precursor in a small number of kindreds. Mechanisms for an apparent “precursor” might involve a delayed mutation, genetic mosaicism, or a submicroscopic balanced chromosomal translocation.
A phase I study of AEE788, a multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, to determine safety, PK and PD in patients (pts) with advanced colorectal cancer (CRC) and liver metastases
Authors: H. Q. Xiong, C. Takimoto, F. Rojo, D. Davis, J. Huang, J. L. Abbruzzese, M. Dugan, A. Thomas, A. Mita, W. P. Steward
Journal: Journal of Clinical Oncology (2007)

4065 Background: AEE788 (AEE) is an oral inhibitor with potent activity against EGFR, ErbB2, and KDR. This phase I study was to assess the safety, PK, PD, and MTD/DLT of AEE in pts with CRC and liver metastases. Methods: AEE was given PO at 25, 50, 100, 250, 300 or 400 mg/day daily in 28-day cycles (C) to 3–6 pt cohorts. 24-hr PK was obtained on C1, days (D)1, 15 and 28. PK parameters of AEE and active metabolite, AQM674 (AQM) were computed by non-compartmental methods. PD markers were analyzed in skin (SK), and tumor (TU) biopsies pre- and post-treatment. Samples were evaluated by both IHC and Laser Scanning Cytometry (LSC). DCE-MRI was performed at baseline (BL), and on C1D2 and 28 and C2D28. Results: 22 pts were treated at doses of 25 (n=4), 50 (n=3), 100 (n=4), 250 (n=1), 300 (n=4), and 400 mg (n=6). No DLT was reported. The most common AE (&gt; 15%): fatigue (55%), vomiting (46%), diarrhea (41%), nausea (36%), dyspnoea (23%), constipation (18%) pyrexia (18%) and rash (18%). 2 pts had reversible gr 3/4 LFTs. Serum concentration of AEE and AQM increases with dose and dose duration. 7 pts had stable disease at the end of C2. Median time on treatment was 56 days (range 7–168). In SK, at doses =100 mg, pEGFR, pMAPK and Ki67 were inhibited by an average of 51, 54 and 41%, respectively by IHC. In endothelial cell (EC) pKDR/KDR was significantly inhibited (4-fold) in the wound-induced SK in a dose-dependent manner by LSC. In TU, inhibition of pEGFR, pMAPK and Ki67 at 400 mg was 100%, 90% and 39%, respectively by IHC. EC pKDR decreased with dose, however, trend was not significant. 1 out 15 pts who had BL and end of C1 DCE-MRI had &gt; 40% K trans reduction. Conclusions: A dose dependent inhibition of pKDR, pEGFR, and pMAPK in skin and tumor was observed. However, no significant effects were observed on Ki67 and apoptosis in TU. No dose dependent reduction in K trans from DCE-MRI was observed. These findings were consistent with the lack of clinical activity of AEE up to 400 mg in this patient population. The study has been discontinued without reaching DLT due to safety data from other phase I studies and in favor of different dosing schedules. No significant financial relationships to disclose.
The combination of bevacizumab (B) and erlotinib (E) shows significant biological activity in patients with advanced hepatocellular carcinoma (HCC)
Authors: M. B. Thomas, R. Chadha, M. Iwasaki, K. Glover, J. L. Abbruzzese
Journal: Journal of Clinical Oncology (2007)

4567 Purpose: HCC is the 5 th most common solid tumor worldwide and the incidence is rising in western countries. &gt;75% of patients (pts) have advanced disease and are ineligible for surgical or loco-regional therapies. Existing cytotoxic chemotherapy does not prolong pt survival and can have significant toxicity in cirrhotic pts. HCC are highly vascular tumors, and based on the prevalence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptors (EGFR) in HCC, we are conducting a phase II, single-arm, open-label trial of B and E in pts with HCC. Patients and Methods: Eligibility criteria include biopsy-proven unresectable HCC, Child- Pugh class A or B cirrhosis, bilirubin = 2.0 mg/dL, transaminases (TA)= 5 x ULN, Plts = 50,000 K/UL and ECOG PS = 2. Prior allowed therapies are surgery, external radiotherapy, ablation, chemoembolization (TACE) and one systemic therapy. Pts receive B 10 mg/kg q14 days plus E 150 mg orally daily until PD or unacceptable toxicity. Results: The primary endpoint is the percent of pts alive and progression free (PFS) after 16 wks of therapy based on median PFS of 3–5 mos in published studies. Response is evaluated by RECIST. 29 pts have been enrolled. For all pts, the med. age was 61 (29–77), 24 (82.8%) were male, 19 (65.5%) were Caucasian; ECOG PS 0, 11 pts, PS 1, 18 pts; 6 had prior systemic therapy, and 10 pts had prior TACE. Of the 27 pts evaluable for response, 1 pt confirmed CR, 5 pts PRs (4 confirmed) (22% RR; 5/6 pts 1 st line) 9 pts SD at 16 wks (55% PFS 16 wks); 5 additional pts SD at 8 wks (74% disease control rate). 2 pts PD at 16 wks, 1 pt PD at 8 wks, 2 removed for toxicity (proteinuria, fatigue); 1 early death. 12/14 pts with SD as their best response showed minor tumor shrinkage, decreased tumor vascularity or increased necrosis. Generally B+E are well tolerated; Gr 3–4 toxicities were TA elevation, hyperkalemia, acne (1 pt each), diarrhea, proteinuria (2 pts), GI bleed (3 pts), fatigue (4 pts), hypertension (5 pts). Conclusions: Based on these early encouraging results and favorable toxicity profile, the combination of B + E appears to have significant clinically meaningful biologic activity in HCC. The trial will continue to full accrual of 40 patients. The combination of B + E warrants further study in HCC. No significant financial relationships to disclose.
Need for awareness and monitoring of ocular toxicities (OT) due to weekly docetaxel administration: experience during a trial of neoadjuvant docetaxel (D) and mitoxantrone (M) for patients with high-risk prostate cancer (PC)
Authors: C. S. Higano, T. M. Beer, M. Garzotto, C. W. Ryan, M. Pitzel, C. R. Works, S. P. Hall
Journal: Journal of Clinical Oncology (2004)

4577
Inhibitory Effects of Retinoic Acid or Retinyl Acetate on the Growth of Untransformed, Transformed, and Tumor Cells In Vitro 2
Authors: Reuben Lotan, Garth L. Nicolson
Journal: JNCI Journal of the National Cancer Institute (1977)

The ability of vitamin A derivatives (“retinoids”) to inhibit the growth of 31 untransformed, transformed, or tumor celliines was investigated in vitro. Two retinoids, retinyl acetate and, to a greater extent, retinoic acid (10−5 M), inhibited the growth of certain transformed and tumor cells. According to their sensitivity to these retinoids, cells were divided into the following categories: a) cells not affected (<10% inhibition) or only slightly inhibited (<25%) by retinoids, such as untransformed CHO-K1-pro, BHK, and Balb/3T3 cells, virally transformed SV3T3 (simian virus 40-transformed), MSV3T3 (murine sarcoma virus-transformed), and PyBHK (polyoma virus-transformed), chemically transformed BP3T3 (benzo[a]pyrene-transformed), lymphosarcoma RAW8, and the human fibrosarcoma HT1080; b) cells that were growth inhibited (25–50%), such as neuroblastoma C1300, mouse mammary adenocarcinomas M12 and DD3, human breast carcinosarcoma HS0578, and the murine lymphomas S49 and EL4; c) cells that were moderately growth inhibited (50–75%), such as mouse sarcoma S180, mastocytoma P815, mammary adenocarcinoma Mm5mT, myeloma S194, lymphoma BW5147, and rat mammary adenocarcinoma R3230AC; and d) cells that were extremely sensitive to retinoids (growth inhibited >75%), such as murine melanomas B16 and S91, rat mammary adenocarcinomas 13762NF and DMBA#8, murine lymphosarcoma RAW117 and myeloma P3, human lymphoid cell line RPMI 1788, and Burkitt's lymphoma (DAUDI). The findings showed that the growth of a considerable number of transformed and tumor cells could be inhibited in vitro by retinoids and suggested that the previously observed antitumor activity of retinoids in vivo is at least partly due to direct inhibition of cell proliferation.
Ductal carcinoma in situ (DCIS) breast specimens need to be embedded completely in order to determine the correct extent of the disease
Authors: K. Bendrat, G. Georgiev, H. Corterier, K. Friedrichs, C. Lindner, A. Niendorf
Journal: Journal of Clinical Oncology (2007)

11061 Background: The processing of breast specimens suspicious of ductal carcinoma in situ (DCIS) is hampered by the fact that DCIS is not regularily visible at the gross level. There is no general consensus as how to process those breast specimens. Suggestions lead from examination of the entire tissue sample with a special focus on the resection margins to algorithms such as cutting only those paraffin blocks containing calcifications. Methods: In order to identify the influence of the diagnostic method on the measured extent of a DCIS lesion we compared two approaches. One was based on the examination of a single section and the other on examination of the entire specimen, i.e. cutting multiple 0.5 cm slices to be analyzed as max. 52 x 76 mm whole mount sections. 187 consecutive breast specimens from 186 patients (median patient age 60 years, range 31 to 87 years) from three gynecological institutions between Jan 2004 and Nov 2006 were searched for DCIS. We compared the largest tumor diameter from a single section of a specimen (‘apparent diameter‘, AD) with a ‘reconstructed diameter‘ RD calculated on the basis of the number of 0.5 cm slices taken from a sample and the number of slices containing the DCIS lesion. Results: Complete histological examination of these 187 cases (90 high and 97 low grade DCIS lesions) revealed a statistically significant difference (p=7.5E-9) between the apparent diameter AD (mean 22.4 mm, range 2 to 80 mm) and the reconstructed diameter RD (mean 31.6 mm, range 6 to 76 mm). In 138 cases (73.8%) the true extent of the disease would have been underestimated (RD &gt; AD) if the diagnosis had been based only on a single exemplary section, the mean difference RD-AD being 14.8 mm (range 1–50 mm). In addition, we found 40 invasive cancers (multifocal inside the DCIS lesion, unifocal inside the DCIS and unifocal outside the DCIS). Conclusions: We conclude that the complete examination of a breast specimen helps to determine the true extent of DCIS and additionally helps to identify cases that turn out to be already invasive. Both findings may have important impact on the patients’ further treatment and outcome. No significant financial relationships to disclose.
Response to anti-PD1/PDL1 therapy in patients with metastatic desmoplastic melanoma.
Authors: Zeynep Eroglu, Dae Won Kim, Douglas Buckner Johnson, Alain Patrick Algazi, Rodrigo Ramella Munhoz, Elizabeth Liniker, Ben Kong, Neharika Khurana, Bartosz Chmielowski, Jeffrey Alan Sosman, Richard A Scolyer, Matteo S. Carlino, Michael Andrew Postow, Wen-Jen Hwu, Georgina V. Long, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

9011 Background: Higher overall burden of somatic mutations in tumors may be associated with better response rates to immunotherapy. Desmoplastic melanoma (DM) is a rare subtype of melanoma comprising approximately 1% of cases. Since DM has been reported to have a higher mutational load than other sub-types of melanoma, we hypothesized that patients with metastatic DM may respond more frequently to anti-PD1 or anti-PDL1 immunotherapies. Methods: A retrospective analysis of over 1000 melanoma patients treated with anti-PD1/PDL1 therapies among seven institutions (UCLA, MD Anderson, UCSF, Memorial Sloan Kettering, Vanderbilt, Melanoma Institute Australia, and Westmead) was conducted to identify patients with DM. We assessed objective response rates (ORR), overall survival (OS), and progression-free survival (PFS). Results: We identified 23 patients with stage IV DM (either pure or mixed subtype), 2 with stage M1a, 11 with M1b, and 10 with M1c disease. Eighteen patients had received prior systemic therapy, including 12 whose disease progressed following ipilimumab. Three patients were treated with nivolumab (anti-PD1 antibody, doses 0.1 or 3 mg/kg), 1 with nivolumab (3mg/kg) plus ipilimumab (1 mg/kg), 3 with BMS-936559 (anti-PDL1, 0.1 or 0.3 mg/kg), and 16 with pembrolizumab (anti-PD1, 2 or 10 mg/kg). Patients received a median of 9 cycles of therapy. A RECIST ORR of 70% was observed, including 9 complete responses and 7 partial responses (3 with > 75% decrease in tumor size per RECIST criteria). Median length of follow-up was 13.4 months. Three patients with eventual isolated progression underwent surgical excision without further disease progression, and only 2 of 23 patients received subsequent systemic therapy. Eighteen patients were alive at last follow-up; Kaplan-Meier median OS (range 2.8 months to 3.5+ years) and median PFS (range 1.4 months to 2.7+ years) were not reached. Conclusions: Patients with metastatic DM appear to have higher response rates and favorable clinical outcomes to anti-PD/PDL1 therapy compared to other patients with advanced melanoma. Additional mechanistic studies are ongoing.
The crucial role of IL-10 in the anti-inflammatory effects of aerobic exercise in a model LPS-induced ARDS
Authors: Rodolfo P. Vieira, Manoel C. Oliveira-Junior, Ricardo W Teixeira, Flavia R. Greiffo, Vanessa R. Silva, Paulo R. Pereira, Adilson S.A. Sousa, Regiane Albertini, Luis V.F. Oliveira, Ana Paula Ligeiro-Oliveira
Journal: European Respiratory Journal (2013)

Recent studies show that low intensity aerobic exercise reduces lung inflammation. These studies demonstrated that anti-inflammatory effects of exercise are mediated by IL-10. Therefore, aiming to investigate the role of IL-10 mediating the exercise effects in the pulmonary inflammation, this study used IL-10 -/- mice subjected to 5 weeks of low intensity aerobic exercise treadmill training in a model of acute inflammation induced by LPS (10ug/mouse intra-tracheally). C57Bl/6 IL-10 +/+ and IL-10 -/- male mice (n = 5) were distributed in Control (IL-10 +/+), Exercise (IL-10 +/+), LPS a (IL-10 +/+ + LPS), LPS b (IL-10 -/- + LPS), LPS + Exercise a (IL-10 +/+) and LPS + Exercise b (IL-10 +/+ + LPS). The results showed that LPS in IL-10 +/+ mice presented increased number of neutrophils in BALF and in lung parenchyma, and also increased levels of IL-1beta, IL-6 and TNF-alpha in BALF and serum compared with Control group (p0.001). In IL-10 -/- mice, LPS showed still higher number of neutrophils in BALF and in lung parenchyma, and also increased levels of IL-1beta, IL-6 and TNF-alpha in BALF and serum when compared with IL-10 +/+ mice (p0.01). On the other hand, exercise in LPS stimulated IL-10 +/+ mice reduced the number of neutrophils in BALF and in lung parenchyma, as well as the levels of IL-1beta, IL-6 and TNF-alpha, while increased the levels of IL-10 (p0.01). On contrary, IL-10 -/- mice stimulated with LPS and subjected to exercise, did not present reduction of neutrophils in BALF and parenchyma and IL-1beta, IL-6 and TNF-alpha levels. Therefore, we conclude that IL-10 is essential for the anti-inflammatory effects of aerobic exercise on acute lung inflammation.
Ultrastructural localization of osteopontin in the kidney
Authors: K M Madsen, L Zhang, A R Abu Shamat, S Siegfried, J H Cha
Journal: Journal of the American Society of Nephrology (1997)

Osteopontin is a secreted phosphoprotein that is expressed in the normal kidney and induced during various pathologic conditions associated with tubulointerstitial injury. However, the exact cellular location of osteopontin in the kidney has been a matter of controversy, and little is known about the role of osteopontin in the kidney. The purpose of this study was to establish the cellular and intracellular distribution of osteopontin in the rat kidney under normal conditions and after injection of a bacterial endotoxin lipopolysaccharide (LPS). Animals received injections of LPS or vehicle at different time intervals from 4 to 20 h before sacrifice. Kidneys were preserved by in vivo perfusion with paraformaldehyde-lysine-periodate (PLP) and processed for light and electron microscope immunocytochemistry using monoclonal antibodies to rat osteopontin. By light microscopy, immunostaining was observed in the descending thin limb and the papillary surface epithelium of both control and LPS-treated animals. After injection of LPS, osteopontin immunostaining was observed throughout the distal nephron and was also present in segments of the proximal tubule, where it was distributed in a punctate pattern. Staining was already present 4 h after injection of LPS and was maximal 6 h after injection. Electron microscopy revealed that osteopontin immunoreactivity in the descending thin limb and distal tubule cells was located in the Golgi apparatus and in small cytoplasmic vesicles, whereas in the proximal tubule labeling was observed in the vacuolar-lysosomal system. Western blot analysis demonstrated a band at approximately 70 kD and confirmed the increase in osteopontin expression after administration of LPS. These results demonstrate that osteopontin is constitutively expressed in cells of the descending thin limb and papillary surface epithelium and is induced throughout the distal tubule after administration of LPS.
Proximal tubule-derived colony stimulating factor-1 mediates polarization of renal macrophages and dendritic cells, and recovery in acute kidney injury
Authors: Yinqiu Wang, Jian Chang, Bing Yao, Aolei Niu, Emily Kelly, Matthew C. Breeggemann, Sherry L. Abboud Werner, Raymond C. Harris, Ming-Zhi Zhang
Journal: Kidney International (2015)