tbuckley/cabot-search huggingface dataset:
A phase I dose escalation study of pemetrexed in patients with advanced head and neck squamous cell cancer (HNSCC)
Authors: P. H. Morrow, B. S. Glisson, L. E. Ginsberg, S. M. Lippman, M. S. Kies, G. R. Blumenschein, R. C. Ayuste, L. Feng, V. A. Papadimitrakopoulou, E. S. Kim
Journal: Journal of Clinical Oncology (2007)

6055 Background: Despite recent advances in therapy, patients (pts) with recurrent or metastatic HNSCC continue to demonstrate a poor median survival. In these pts, early trials with pemetrexed, a novel antimetabolite that acts upon several enzymes involved in pyrimidine and purine synthesis, have demonstrated promising efficacy and tolerability. Prior studies found that the administration of oral dexamethasone with pemetrexed reduced the incidence of skin rash. Later, vitamin supplementation (B12 and folic acid), given in addition to the dexamethasone, further diminished side effects. However, no trial has yet evaluated the appropriate steroid dose and its relation to the dosing of pemetrexed, in the setting of vitamin supplementation. We conducted a phase I trial to determine the maximum tolerated dose, toxicity, and preliminary efficacy of pemetrexed when given with different schedules of, or in the absence of, dexamethasone in pts with advanced HNSCC who had been treated with at least one or more chemotherapy regimens. Methods: Eligible pts had metastatic or recurrent HNSCC, prior treatment with one or more chemotherapy regimens, ECOG PS =2, and life expectancy &gt;3 months. A conventional algorithm-based dose escalation design was applied, with three predefined dose levels (DL) of pemetrexed (500 mg/m 2 , 600 mg/m 2 , and 700 mg/m 2 ) within each schedule of dexamethasone (none, 20 mg IV on day 1, and 4 mg orally bid for 3 days). Results: A total of 23 pts have been enrolled; 18 pts were evaluable. Median age was 57 years (range 47–82). Median ECOG PS was 1 (range 0–2), and 75% of pts were male. Number of prior chemotherapy regimens were as follows: 1 (40%), 2 (35%), 3 (15%), and 4 (10%). Preliminary data demonstrated only 2 treatment-related adverse events that were grade 3 or greater: anemia (DL1) and pneumonia (DL 1). In all, 13 pts have received pemetrexed with less than standard recommended dexamethasone dosing (none or IV), including 7 pts who received no dexamethasone. Of the 18 evaluable pts, 1 pt had a partial response and 2 pts had stable disease. Conclusions: This represents the first study that demonstrates that steroids may not be required as premedication with pemetrexed. Due to the limited toxicity observed, trial enrollment continues with dose escalation. [Table: see text]
Combination chemotherapy with cis-diamminedichloroplatinum and vinblastine in advanced non-small cell lung cancer.
Authors: T M Woodcock, M S Blumenreich, S P Richman, T T Kubota, P S Gentile, J C Allegra
Journal: Journal of Clinical Oncology (1983)

Twenty-seven patients (25 males and 2 females) with histologically confirmed, unresectable, or metastatic non-small cell lung cancer were entered on a combination chemotherapy protocol including cisplatinum and vinblastine sulfate (DDP)(VLB). Patients had to have measurable disease as defined by the presence of two clearly measurable perpendicular diameters, be untreated with either chemotherapy or radiation therapy, and give informed consent to be eligible for study entry. The median age was 57 yr and the median performance status was 70 (Karnofsky scale); 10 patients had epidermoid carcinoma, 9 adenocarcinoma, 4 large cell carcinoma, and 4 undifferentiated carcinoma. All patients had intrathoracic disease, 12 also had extrathoracic lymph node involvement, 8 bone involvement, 2 liver metastasis, and 2 central nervous system metastasis prior to beginning chemotherapy; 9 patients had involvement of one site, 12 of two sites, 5 of three sites, and 1 of four sites. Cisplatinum was given as a short intravenous infusion of 120 mg/m2 on days 1 and 28, and then every 6 wk. Vinblastine was administered as an intravenous injection of 8 mg/m2 on days 1, 14, and 28, and then every 3 wk. Patients were evaluated prior to each course of cisplatinum. If progression occurred, therapy was discontinued. If stabilization or response was noted, then therapy was continued until intolerable toxicity or progression supervened. Every patient entered is considered evaluable for toxicity and response. There were no complete remissions; 14 patients achieved a partial response, 3 had a minimal response, 5 had stabilization of their disease, 1 had disease progression, and 4 are considered to have had drug deaths. Responses were seen after the first cisplatinum course in 13 patients and after the second in 1. Toxicities seen were universal nausea and vomiting; elevation of creatinine occurred in 6 patients, ranging from 2.1 to 14.6 mg/dl, and was clinically significant in 2 patients. Myelosuppression, with a leukocyte nadir of less than 3.0 X 10(9)l in 10 cases and platelet nadir of less than 100.0 X 10(9)l was seen in 5 cases and partial hearing deficit occurred in 2 patients. Median survival was 22 wk for the whole group (24 wk for the whole group if the 4 early drug deaths are excluded). Median survival was 26 wk for responding patients and 13 wk for nonresponding patients (remains the same if the early deaths are excluded from the latter group).(ABSTRACT TRUNCATED AT 400 WORDS)
Correlation of dynamic contrast enhanced magnetic resonance imaging (DCE MRI) with <sup>18</sup>f-fluoromisonidazole positron emission and computed tomography (<sup>18</sup>F-FMISO PET/CT) in assessing tumor hypoxia in a series of head and neck cancer (HNC) patients with nodal metastases
Authors: N. Lee, J. Jensen, H. Schoder, Y. Wang, M. Fury, D. G. Pfister, H. Stambuk, J. Humm, J. Koutcher, A. Shukla-Dave
Journal: Journal of Clinical Oncology (2009)

6083 Background: 18 F-FMISO PET/CT is a noninvasive hypoxia imaging modality. Hypoxia can develop within the tumor which typically corresponds to regions with poor blood perfusion. DCE-MRI can yield results on tumor perfusion. The present study compares hypoxic and perfusion status of HNC with nodal metastases using DCE-MRI and 18 F-FMISO PET/CT imaging. Methods: 13 HNC (7 base of tongue, 5 tonsil, 1 larynx) patients with nodal metastases underwent both DCE-MRI and 18 F-FMISO PET/CT scans prior to chemoradiotherapy. MRI was performed on a 1.5 Tesla GE Excite scanner. DCE-MRI studies were acquired using a fast multi-phase spoiled gradient echo sequence. Antecubital vein catheters delivered a bolus of 0.1 mmol/kg Gd-DTPA at 2 cc/s. For 18 F-FMISO PET/CT,∼10.0 mCi of 18 F-FMISO was administered IV and images were acquired ∼2 hours later. PET images were reconstructed; CT data were used for attenuation correction. Region of interests (ROIs) were manually drawn by a neuroradiologist. Quantitative DCE-MRI analyses were done using the 2-compartment Tofts model. The analyses calculated the pixel K trans (distribution rate constant), v e (extravascular-extra-cellular volume fraction), and k ep (redistribution rate constant). 18 F-FMISO PET/CT images were analyzed and the uptake by the tumor was scored as: no uptake (score 0); moderate-severe uptake (score 1). Semi-quantitative analysis included standardized uptake value (SUV) measurements. Statistical significance was calculated using a 2-sided Student's t-test, with p &lt; 0.05. Results: A total of 17 nodes were analyzed. For the nodes that showed no hypoxia on PET imaging (n = 7), the mean (±SD) values were: 18 F-MISO SUV (1.1 ± 03), K trans (0.33 ± 0.18), v e (0.53 ± 0.23), and k ep (0.66 ± 0.25). For the nodes that showed moderate to severe 18 F-MISO uptake (n = 10) the values were: 18 F-FMISO SUV (2.8 ± 08), K trans (0.24 ± 0.07), v e (0.61 ± 0.13), and k ep (0.43 ± 0.17). A significant lower k ep for nodes with 18 F-MISO uptake (p = 0.042). Conclusions: Preliminary result supports the hypothesis that the hypoxic nodes are poorly perfused nodes (lower k ep values) versus nodes with no hypoxia. No significant financial relationships to disclose.
간세포암종 환자의 종양 조직 내 P-glycoprotein 및 p53 단백의 발현이 항암화학요법의 반응률에 미치는 영향
Authors: 정진모(Jin Mo Chung), 조현호(Hyun Ho Cho), 김영호(Young Ho Kim), 조광희(Kwang Hee Cho), 조상형(Sang Hyung Cho), 최대현(Dae Hyun Choi), 정숙향(Sook Hyang Jeong), 이진혁(Jin Hyuk Lee), 한철주(Chul Ju Han), 김유철(You Cheoul Kim), 이진오(Jhin Oh Lee), 정진행(Jin Haeng Chung), 이승숙(Seung Sook Lee)
Journal: Clinical and Molecular Hepatology (2001)

Background / Aims : Hepatocellular carcinoma(HCC) is a drug -resistant tumor. The expression of a multidrug resistant gene, P-glycoprotein(P-gp) is a major mechanism of drug resistance. The aims of our study were, firstly, to observe the expression rate of P-gp in HCC tissue obtained by percutaneous fine needle aspiration(PCNA) from stage IV HCC patients; secondly to examine the association between P-gp and chemotherapeutic response ; and finally to investigate the correlation between p53 protein expression and P-gp expression. Subjects and Methods : We studied 29 cases of stage IV HCC treated by systemic chemotherapy. Expression of P-gp and p53 were evaluated by immunohistochmical staining of HCC tissue with human monoclonal anti body, JSB-1(Anti P-gp ) and DO-7(Anti p53), respectively. We analyzes the results of immunohistochmical staining of HCC tissues of the patients in relation to chemotherapeutic response and other clinical charateristics. Results : The expression rate of P-gp was 27.5%. Partial response to anti-cancar chemotherapy was observed in 16.7% of the to chemotherapeutic response, none of the response to anti-caner chemotherapy was observed in 16.7% of the patients. Although we could not see a statisrically significant association between to chemotherapeutic response expression and chemotherapeutic response , none of the response patients showed chemotherapeutic response P-gp expression. p 53 protein expression was found in 45% of the patients. There was no significant correlation between p 53 protein expression and P-gp expression. Conclusions : Although the number of our study subjects was small, chemotherapy- responsive patients didn`t show P-gp expression. P-gp expression might be used as a predictor of response to potentially toxic anti-cancer chemotherapy in HCC patients. Futher study is warranted to confirm our results.
Stroke following therapy for Hodgkin's Disease (HD): A report from the Childhood Cancer Survivor Study (CCSS)
Authors: D. C. Bowers, D. E. McNeil, Y. Liu, Y. Yasui, M. Stoval, J. G. Gurney, M. M. Hudson, L. L. Robison, K. C. Oeffinger
Journal: Journal of Clinical Oncology (2004)

8523 Background: An increased risk for strokes has not been previously reported among HD survivors. This report examines the rate and risk factors for stroke in long-term survivors of HD. Methods: The CCSS is a multi-institutional cohort study of long-term (≥ 5 years) survivors who were diagnosed between 1970–1986. The rate of first occurrence of self-reported strokes was determined for HD survivors (N=1665) and compared with a random sample of siblings of childhood cancer survivors (N=3846). The mean age at interview of the HD survivors was 31.9 years of age, with a mean age at diagnosis of 14.6 years. The incidence rates of HD survivors at ≥ 5 years post diagnosis and siblings were calculated separately. Cox proportional hazards models were used to estimate rate ratio (RR) of developing stroke between HD survivals and siblings. Results: Fifteen HD survivors reported a stroke: one during therapy, 13 occurring ≥ 5 years after HD diagnosis, and one without an age at stroke reported. The rate of stroke in HD survivors ≥ 5 years post diagnosis was 0.68 per 1000 person-years (95% CI, 0.40–1.18). Of the 13 late occurring strokes, all had chest/mantle radiation (median dose 40 Gy), with a median interval of 15 years from HD diagnosis to stroke. The median age of stroke was 31 years (range 21–40). Seven siblings reported a previous stroke, with a rate of 0.069 per 1000 person-years (95% CI, 0.03–0.15). The RR of stroke for all HD survivors, in comparison with siblings, was 3.88 (95% CI, 1.46–10.3; p = 0.0065). The rate of stroke for HD survivors who were treated with chest radiation therapy (RT) was 0.82 per 1000 person-years (95% CI, 0.48–1.41). Compared to siblings, the RR of HD survivors treated with chest RT was 4.28 (95% CI, 1.6–11.2; p=0.0031). Anthracycline exposure, treatment with chemotherapy only, hypertension and diabetes mellitus were not associated with an increased risk of stroke. Conclusions: Though an infrequent outcome, survivors of childhood HD may be at an increased risk of stroke. In this study, previous exposure to chest RT was strongly associated with risk of stroke. Because the risk may be modified by prevention, it is imperative to further study this process. No significant financial relationships to disclose.
Lower airway inflammation and hyperresponsiveness in allergic and non-allergic rhinitis
Authors: Yanqing Xie, Jiaxing Xie, Kefang Lai, Nanshan Zhong
Journal: European Respiratory Journal (2011)

Background: Remarkable relationship exists between upper and lower airways, but lack of large-sample study on total airway inflammation and hyperresponsiveness in allergic and non-allergic rhinitis.

Objectives: To investigate lower airway inflammation and hyperresponsiveness in allergic and non-allergic rhinitis without asthma.

Methods: We enrolled 166 subjects with allergic rhinitis (AR), 122 with non-allergic rhinitis (NAR) and 143 healthy volunteers (control). Nasal-lavage, induced sputum, lower airway fractional exhaled nitric oxide (FeNO), methacholine bronchial provocation tests and allergen skin prick test were performed.

Results: AR group showed high nasal-lavage eosinophils count [6.90 (22.40)/×200]. Sputum eosinophil was 1.50% (5.38%) in AR, higher than NAR [0.25% (1.00%)] and control [0% (0.50%), P  3%) showed statistical difference ( P <0.05) in nasal eosinophils [15.65 (41.60)/×200 vs.2.05 (14.45)/×200], FeNO [31.61±21.52ppb vs.19.96±14.34ppb], mild and borderline BHR count [13 (22.03%) vs.7 (6.54%)] when compared with 107 cases without sputum eosinophils increased.

Conclusions: Allergic rhinitis presents obvious upper/lower airway inflammation and BHR when compared with non-allergic rhinitis. High sputum eosinophil level in allergic rhinitis is closely correlated with nasal eosinophils, FeNO and BHR.
Phase II study of topotecan and carboplatin in the treatment of platinum-sensitive recurrent ovarian and peritoneal cancer
Authors: P. Hanjani, M. S. Shahin
Journal: Journal of Clinical Oncology (2006)

15001 Background: The aim of this trial was to investigate the efficacy and toxicity of the combination of Topotecan (T) and Carboplatinum (C) in the management of recurrent platinum sensitive ovarian and peritoneal cancer. Methods: T (1 mg/m 2 ) was given as a 30-minute infusion daily × 3 days and C (AUC 5) was given as a 30-minute infusion following T on day 3 on a 21-day cycle. Results: Thirty patients (pts) were enrolled and all pts were evaluable for response and toxicity. Mean age was 63.2 (range = 44–84). One hundred eighty five cycles (mean/pt = 6, range 2–10) were evaluable for toxicity. Dose escalation (T = 1.25 mg/m 2 ) was possible in 25 (83.3%) pts. Hematologic toxicity grade 3 and 4 neutropenia was seen in 60 (32.4%) and 10 (5.4%) cycles, respectively. Grade 3 thrombocytopenia was encountered in 24 (13%) cycles. Grade 3 Hgb was observed in 4 (2.2%) cycles. No grade 4 thrombocytopenia/Hgb or neutropenic fever was encountered. Blood transfusions were required in 9 (4.9%) cycles. Bone marrow support with erythropoiten (40% pts), and filgrastim (43.3% pts) were utilized. No neuropathy &gt; grade 1 was encountered. Fourteen pts (46.6%) pts had a hypersensitivity reaction to C and successful desensitization was carried out in 8 (57.1%). Mean follow-up interval was 16.9 months (mos) (Range 1.7–43). To date, 6 (20%) pts are alive without disease, 16 (53.3%) are alive with disease, and 8 (26.7) have died of disease. The overall response rate was 83.3% (5 CR and 20 PR). Five (16.6%) pts had SD. Median progression-free interval was 8.2 mos. Overall mean survival for the cohort was 31.2 mos (95% CI: 24.47–37.71). Conclusions: Given the ICON-4 data, supporting combination therapy in recurrent platinum-sensitive patients, this regimen provides an effective and tolerable alternative to Taxane-platinum combination with no significant neuropathy. This regimen is especially attractive in patients who have significant residual neuropathy after initial treatment. Carboplatinum desensitization was feasible in previously pre-treated patients. No significant financial relationships to disclose.
Postmortem examination should always be carried out for deaths due to trauma
Authors: I. S D Roberts, E. W Benbow
Journal: BMJ (1996)

EDITOR,—S J Calder and colleagues' study of the certification of the cause of death in patients who die soon after proximal femoral fracture revisits a phenomenon that has been recognised for many years.1 Death certificates and pathologists' reports to coroners are often written in ways deliberately designed to avoid an inquest,2 3 and this practice leads to underreporting of certain lesions in official mortality statistics. Such lesions include proximal femoral …
Protein Catabolism and Acid Phosphatase Activity in Mixed Normal and Neoplastic Human Cell Cultures
Authors: Ed Miedema
Journal: JNCI Journal of the National Cancer Institute (1969)

This study had two objectives: 1) to select a suitable marker for identification of individual cell types in mixed cultures; 2) to seek biochemical evidence as to whether nonmalignant diploid and malignant human cells were interacting in mixed culture beyond simple physical contacts owing to their proximity in culture. For the first objective it was found that alkaline phosphatase activity localized by histochemical staining technique was a reliable quantitative and qualitative marker for distinguishing HEp-2 human carcinoma strain from JAM diploid fibroblast cells. For the second objective it was found that these human carcinoma cells inhibit the catabolism of protein by diploid human fibroblast cells in mixed culture. Further, the activity of one acid hydrolase, acid phosphatase, appeared reduced in mixed cultures. No change in the activity of the specific cell-marker alkaline phosphatase was noted as a consequence of cellular interaction in mixed culture.
California doctor convicted of murder over deaths of three patients by overdose
Authors: Michael McCarthy
Journal: BMJ (2015)

A California doctor has been convicted of second degree murder for overprescribing drugs that caused fatal overdoses in three of her patients. Prosecutors said it was the first time in the United States that a doctor had been convicted for murder for overprescribing drugs.

A jury of 10 women and two men handed down the verdict in Los Angeles County Superior Court on 30 October, finding the doctor, Hsiu Ying “Lisa” Tseng, 45, guilty of 23 counts, including 19 counts of prescribing …
NICE recommends pulmonary rehabilitation programmes for patients with COPD
Authors: Jacqui Wise
Journal: BMJ (2016)

Patients with stable chronic obstructive pulmonary disease (COPD) and exercise limitation due to breathlessness should be referred to a pulmonary rehabilitation programme, the National Institute for Health and Care Excellence (NICE) has recommended.

The updated quality standard from NICE1 also recommended that patients admitted to hospital for an acute exacerbation of COPD should start a pulmonary rehabilitation programme within four weeks of discharge. NICE said that this reduces the short term risk of hospital readmission, as well as improving the quality of life and the …
Phase II protocol with docetaxel plus prednisone in patients with hormone refractory prostate cancer in two groups: With previous chemotherapy and without chemotherapy
Authors: E. Chiti, F. Calais da Silva
Journal: Journal of Clinical Oncology (2008)

16118 Background: Although treatment of hormone-refractory prostate cancer (HRPC) is difficult, the use of docetaxel every 21 days plus prednisone has been reported as a promising regimen for patients with HRPC. The purpose of this study was the investigation of the efficacy of docetaxel for patients with HRPC and its toxicity. Methods: 95 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and 75 mg of docetaxel per square meter every three weeks. Their mean age was 72 (43-91) years, their median prostate-specific antigen (PSA) level was 204 (38–1100) ng/ml, and the median Gleason score was 8 (7 to 9). Results: Among the 95 patients, 76 patients are evaluated and 19 are not evaluated ( 9 patients are still on chemotherapy and 10 with less than 2 cycles). In 76 evaluated patients 43 (57%) didn’t had previous chemotherapy and 33 (43%) had previous chemotherapy. There is no difference in median age (72 vs 70), median PSA (247 vs 220), median cycles (8 vs 7) or median Follow Up (15 vs 12). There were 5 reported drug related Grade 3 toxicities, dermatological. Only five patients required a blood transfusion. PSA response without previous chemotherapy (nº patients) - 27 (63%) PSA response with previous chemotherapy - 9 (27%) PSA stable without previous chemotherapy - 11(25%) PSA stable with previous chemotherapy - 14(43%) PSA progression without previous chemotherapy - 5(12%) PSA pregression with previous chemotherapy - 10 (30%) Survival Status without previous chemotherapy (43 patients) - 15 months (3–30) Survival Status with previous chemotherapy (33 patients) - 12 months (3–41). Conclusions: Docetaxel plus prednisone is a safe regimen in previous poly-chemotherapy treated hormone refractory prostate cancer patients and still with a good response and efficacy and should be done in first line if chemotherapy. Patients that didn’t had previous chemotherapy live longer (15 months) than whose had previous chemotherapy (12 months). There is a high response in the patients who had Docetaxel in first line of chemotherapy 27 patients (63%), second line 9 patients (27%). No significant financial relationships to disclose.
New Strategies in Breast Cancer: Immunotherapy
Authors: Lajos Pusztai, Thomas Karn, Anton Safonov, Maysa M. Abu-Khalaf, Giampaolo Bianchini
Journal: Clinical Cancer Research (2016)

Abstract More than 70% of breast cancers contain lymphocytic infiltration in the stroma, and preclinical studies suggest that immunoediting and partial control of cancer progression by the local immune microenvironment operate in most breast cancers. Consistent with this hypothesis, a large number of studies demonstrated a favorable prognostic and chemotherapy response predictive role for immune infiltration in breast cancer. The evidence is particularly strong for triple-negative and HER2-positive cancers. The development of clinically effective immune checkpoint inhibitors now provides an opportunity to test the therapeutic potential of augmenting the local antitumor immune response. Several phase I clinical trials using single-agent anti–PD-1 and anti–PD-L1 antibodies demonstrated objective tumor response rates, with remarkably durable responses, in heavily pretreated, metastatic, triple-negative cancers and somewhat lower responses in estrogen receptor–positive cancers. Currently, close to 50 ongoing, or soon to open, clinical trials evaluate the role of this new treatment modality in breast cancer. Clin Cancer Res; 22(9); 2105–10. ©2016 AACR.