tbuckley/cabot-search huggingface dataset:
Front-line topotecan (T) with or without whole-brain radiation (WBRT) followed by alternating T and platinum/etoposide (PE) for patients (Pts) with small cell lung cancer (SCLC) and brain metastases (mets).
Authors: R. E. Sanborn, J. M. Holland, W. Pierce, P. A. Rasmussen, S. Seung, T. Coffey, H. J. Ross
Journal: Journal of Clinical Oncology (2010)

e18100 Background: T is active in relapsed SCLC and reaches the CNS. Eligible pts with SCLC and brain mets received 2 cycles of T, then alternating PE/T. WBRT was given concurrently for symptomatic brain mets. Methods: Prior PE was allowed, including one PE cycle at entry. Pts received T 1.5 mg/m2/d iv D 1-5 × 2 21D cycles. For history of hematologic compromise; T = 1.2 mg/m2/d D #1-5. Responding pts alternated PE (cisplatin 60 mg/m2 or carboplatin AUC 5 D #1 + E 120 mg/m2 D #1-3, 21-D cycles) with T for up to 8 cycles. Symptomatic brain mets received WBRT with 50% dose reduction cycle 1 T. Primary endpoint was response (OR), with planned 2-stage design (19 pts first; 39 pts second assessment). Results: 15 pts were treated (1999-2004) before the study was closed due to slow accrual. Pt characteristics: Male/female (no.) = 10/5; median age = 66; ECOG PS 0/1/2 (no.) = 4/7/4. 6 received prior PE. Median cycles = 5 (1-8). 4 pts received concurrent WBRT. SAEs occurred in 12 pts. Hematologic (Gr 3/4): anemia (2/1); neutropenia (3/5); leukopenia (2/3); thrombocytopenia (2/3); bleeding (1 Gr 3); neutropenic fever/sepsis (3). Non-hematologic (Gr 3/4): fatigue (1 Gr 3); SOB (2); headache (1); cellulitis (1 Gr 4); pneumonia (3); hyperglycemia (1 Gr 4); nephrolithiasis (1 Gr 3); aspergillus (1 Gr 4). 3 pts died within 30 days of entry; 2 (GI bleed, pneumonia) while receiving concurrent WBRT, 1 (unknown) after cycle 5. OR = 9/12 evaluable: CR/PR/SD/PD = 0/9/3/0. Median time to progression 4.18 months (2.63-9.23 mo) and brain was the first site of progression in 11/12 pts. Median survival = 10.43 mo (0.37-87.87 mo). Conclusions: While the trial closed early, OR, median survival and TTP were as expected for ED-SCLC. Toxicity was typical for T and PE. Early deaths occurred in 2 of 4 pts treated with T/WBRT but small numbers prevent any conclusions. Up-front T followed by PE/T does not seem to provide an advantage over standard PE/WBRT for pts with ED-SCLC. No significant financial relationships to disclose.
Phosphoinositide 3-kinase δ signaling modulates endoplasmic reticulum stress in aspergillus fumigatus-induced allergic lung inflammation
Authors: Yong Chul Lee, So Ri Kim, Kyung Sun Lee, Yun Hee Ko, Jae Seok Jeong
Journal: European Respiratory Journal (2014)

Phosphoinositide 3-kinase (PI3K)-δ signaling and endoplasmic reticulum (ER) stress are critically involved in various inflammatory processes. However, there is no information concerning their interrelationship in allergic inflammation. In this study, we aimed to elucidate an association of ER stress with PI3K-δ signaling in fungus-induced allergic lung inflammation.Using  Aspergillus fumigatus -exposed  in vivo  and  in vitro  experimental systems, we have investigated the role of PI3K-δ in the regulation of ER stress in the pathogenesis of allergic lung inflammation.The  Aspergillus fumigatus -sensitized and -challenged mice showed that the expression of ER stress markers and the protein levels of unfolded protein response (UPR)-related markers in lung tissues were significantly increased after  Aspergillus fumigatus  challenge. Protein expression of ER stress markers was also remarkably elevated in  Aspergillus fumigatus -stimulated cultured tracheal epithelial cells. However, administration of PI3K-δ inhibitor significantly reduced the increases in ER stress markers and UPR-related proteins in the lung. And, blockade of PI3K-δ signaling using PI3K-δ inhibitor or PI3K-δ specific siRNA also markedly reduced the expression of ER stress markers in  Aspergillus fumigatus -stimulated cultured tracheal epithelial cells. Furthermore, inhibition of PI3K-δ or ER stress improved various pathophysiologic features in  Aspergillus fumigatus -induced allergic lung inflammation.These findings suggest that PI3K-δ signaling is implicated in  Aspergillus fumigatus -induced allergic lung inflammation through the modulation of ER stress.
A phase I evaluation of the quinazoline antifolate thymidylate synthase inhibitor, N10-propargyl-5,8-dideazafolic acid, CB3717.
Authors: A H Calvert, D L Alison, S J Harland, B A Robinson, A L Jackman, T R Jones, D R Newell, Z H Siddik, E Wiltshaw, T J McElwain
Journal: Journal of Clinical Oncology (1986)

CB3717 is a quinazoline antifolate whose cytotoxic activity is mediated by inhibition of thymidylate synthase (TS). A phase I clinical trial commenced in September 1981 and 99 patients have received 296 treatments. Doses were dissolved in 0.15 mol/L NaHCO3 (pH 9.0) at a concentration of 4 mg/mL infused over one hour or in a total volume of 1 L infused over 12 hours. Doses were repeated every 3 weeks. The starting dose of 140 mg/m2 was escalated to 600 mg/m2. Renal toxicity, detected by a decrease in the 51Cr EDTA clearance, was dose-related and occurred in seven of ten patients receiving greater than 450 mg/m2. Reversible hepatic toxicity often associated with malaise occurred in 223 of 288 assessable courses (77%). Fifty-nine courses (20%) were associated with increases in alanine transaminase (ALT) levels to greater than 2.5 times the upper limit of the normal laboratory range. Increases in alkaline phosphatase levels also occurred, but were less marked. The severity and prevalence of these elevations were unaffected by the duration of the infusion. A self-limiting rash appeared in 12 patients and a radiation recall reaction was seen in two. Leukopenia developed in 17 patients (WBC less than 3 X 10(9)/L), and thrombocytopenia occurred in six patients (platelets less than 100 X 10(9)/L). The mean leucocyte nadir occurred on day 10 and was followed by recovery at 11 to 19 days. Neither the incidence nor the severity of any of these latter toxicities was dose related. The maximum tolerated dose was in the region of 600 mg/m2 with renal toxicity being dose limiting, although the inter-patient variation did not allow a precise definition. Seventy-six patients were evaluable for response. Responses occurred at doses greater than or equal to 200 mg/m2 and were ovary, one complete response (CR), one partial response (PR), seven minor responses (MR) in 30 cases; breast, two PRs and one MR in eight cases; adenocarcinoma of the lung, one MR in 5 cases; mesothelioma, one PR in five cases; and colon, two MRs in four cases. CB3717 has activity in heavily pretreated patients. The recommended phase II dose for good-risk patients is 400 mg/m2 using the one-hour infusion schedule of administration.
Phase I/II trial of granisetron: a novel 5-hydroxytryptamine antagonist for the prevention of chemotherapy-induced nausea and vomiting.
Authors: M Addelman, C Erlichman, S Fine, D Warr, C Murray
Journal: Journal of Clinical Oncology (1990)

A new class of antiemetic agents, the 5-hydroxytryptamine (5-HT3) antagonists, have been shown to possess potent antiemetic properties in the ferret model. We conducted a phase I/II trial of the 5-HT3 antagonist BRL43694 (granisetron) in 24 chemotherapy-naïve patients who were receiving any combination of doxorubicin and/or cisplatin. The first 12 patients received 40 micrograms/kg and the second 12 received 80 micrograms/kg of granisetron intravenously before beginning chemotherapy. Nausea was assessed by a patient-completed visual analogue scale and episodes of retching recorded by the patient and an independent observer. Fifty-two percent of the 22 evaluable patients had no retching or vomiting and 32% had no nausea during the first 24 hours after chemotherapy. Pharmacokinetic measurements were performed. The disposition of granisetron was best described using a two-compartment model. The area under the plasma concentration curve (AUC) was 277 +/- 226 ng.h/mL and 359 +/- 282 ng.h/mL at 40 and 80 micrograms/kg, respectively. The total body clearance was 0.319 +/- 0.315 L/kg/hr and 0.483 +/- 0.504 L/kg/hr at the 40 and 80 micrograms/kg doses. Wide interpatient variation in model independent parameters was observed. There was no suggestion of dose-dependent efficacy at the two dose levels studied. We conclude that granisetron shows promise as a well-tolerated and effective antiemetic. Randomized trials comparing this drug with standard regimens are currently underway.
Prognosis and clinical features of ulcerative colitis-associated colorectal cancer in Japan: Results of a nationwide registry over 20 years
Authors: T. Watanabe, T. Konishi, J. Kishimoto, K. Kotake, T. Muto, H. Nagawa
Journal: Journal of Clinical Oncology (2008)

15117 Background: Clinicopathological features of ulcerative colitis (UC)-associated colorectal cancer are not fully clarified due to the small number of the cases compared with sporadic colorectal cancer, especially in the Asian population. This study aims to clarify the prognosis and the clinicopathological features of UC-associated colorectal cancer in the Japanese population compared with sporadic colorectal cancer. Methods: All patients diagnosed as UC before treatment of colorectal cancer or pathologically diagnosed as such in the surgical specimens from 1978 to 1998 were extracted from a large nationwide database of colorectal cancers, Multi-Institutional Registry of Large-Bowel Cancer in Japan. Clinicopathological features and cancer-specific survival were compared between UC-associated colorectal cancer and sporadic colorectal cancer. Results: Among 108,536 cases of colorectal cancers registered between 1978 and 1998, a total of 169 cases of UC- associated colorectal cancers were identified including 121 cases undergoing surgery. Proportion of UC-associated colorectal cancer has increased in the second half of 1990. UC-associated colorectal cancer had younger age, more multiple lesions, higher prevalence of superficial or invasive morphological types, and higher frequency of mucinous or signet ring cell carcinomas compared with sporadic cancer. Overall survival of UC-associated colorectal cancer was significantly poorer than that of sporadic cancer among Dukes’ C cases (p<0.05). Conclusions: UC-associated colorectal cancer has different biological features from sporadic cancer including poor prognosis at the advanced stage. In the light of finding that UC-associated colorectal cancer has increased over ages, the importance of surveillance program should be reminded for early detection of cancer. No significant financial relationships to disclose.
Trabectedin in Patients with Brca Mutated and Brcaness Phenotype Advanced Ovarian Cancer (Aoc): Phase Ii Prospective Mito-15 Study
Authors: D. Lorusso, G. Ferrandina, S. Pignata, R. Sorio, G. Amadio, A.M. Mosconi, C. Pisano, G. Mangili, C. Masini, G. Artioli, F. Narducci, M. Di Napoli, C. Rigamonti, F. Raspagliesi, G. Scambia
Journal: Annals of Oncology (2014)
Effects of recombinant human interleukin-3 in patients with relapsed small-cell lung cancer treated with chemotherapy: a dose-finding study.
Authors: P E Postmus, J A Gietema, O Damsma, B Biesma, P C Limburg, E Vellenga, E G de Vries
Journal: Journal of Clinical Oncology (1992)

The aim of the study was to determine the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after combination chemotherapy and to evaluate the ability of rhIL-3 to influence hematopoietic recovery.Nineteen patients who had relapsed small-cell lung cancer (SCLC) received rhIL-3 after their second course of chemotherapy, which consisted of either cyclophosphamide, doxorubicin, and etoposide (CDE) every 3 weeks or vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. Twenty-four hours after the last chemotherapy dose, rhIL-3 was administered subcutaneously (SC) once daily for 14 days on an outpatient basis. Escalating dosages (1, 2, 4, 8, and 16 micrograms/kg/d) of rhIL-3 were tested. Hematologic effects were evaluated by comparing blood cell recovery after chemotherapy cycle 1 and cycle 2 plus rhIL-3.The adverse effects of rhIL-3 at dosages up to 8 micrograms/kg/d consisted mainly of low-grade fever and flulike symptoms. At 16 micrograms/kg, rhIL-3 headache became dose-limiting. Severe neutropenia (neutrophils less than 0.5 x 10(9)/L) after VIMP cycle 2 was shorter in duration than after cycle 1 (7 v 3 days; P less than .05). At rhIL-3 dose levels 8 and 16 micrograms/kg, hematologic effects in seven patients who were treated with VIMP showed a significant hastened recovery of leukocyte and neutrophil counts during cycle 2 compared with cycle 1 and increased monocyte and eosinophil counts in cycle 2 compared with cycle 1. rhIL-3 also increased reticulocyte and platelet counts at a dose level of 8 micrograms/kg. No significant stimulation of basophils and lymphocytes was observed. Apart from the hematologic effects, rhIL-3 also augmented the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and lowered cholesterol levels.This study demonstrates that rhIL-3 can be safely administered after chemotherapy on an outpatient basis. rhIL-3 is tolerated well at doses up to 8 micrograms/kg/d and is biologically active in patients after myelosuppressive chemotherapy.
Preliminary quality-of-life analysis in patients (pts) submitted to chemo-radiation protocols for locally advanced squamous cell carcinoma of the larynx and oropharynx (SCCLO): Experience of the National Cancer Institute of Brazil
Authors: D. F. Rossi, D. Herchenhorn, F. L. Dias, C. M. Araujo, L. M. Moraes, J. Kligerman, R. A. Lima
Journal: Journal of Clinical Oncology (2004)

5570 Background: Quality of life and organ function analysis are important goals of chemo-radiation protocols for SCCLO. Methods: This is a single institution prospective study, done in SCCLO pts with locally advanced disease-stage III 45,6% and stage IV 54,4%, submitted to chemo-radiation therapy that consisted of Radiotherapy 70Gy in 8 weeks combined with Cisplatin 100mg/m2 3 doses every 3 weeks. Quality of life questionnaires were adapted from international validated protocols and included questions pertinent to our socio-economic reality including voice, dietary and social issues. 25 patients(pts) that completed treatment and were in complete response (organ-preservation) after a medium follow-up of 16,8 months (3–37) responded to the questionnaires. Results: 96% of the pts have oral intake, 88% were able to eat solid food, 20% report some degree of swallowing difficulties and 16% had odinophagia (12% mild and 4% moderate). 88% had appetite and 80% adequate taste, xerostomia was mild in 44%, moderate in 8% and severe in 16% (total 68%), only 4% had enteral feeding and 80% were able to eat in public places, 80% refer pleasure during eating. 64% consider voice quality good or satisfactory and 96% were able to make inter-personal or telephone communication.16% of the pts report some degree of depression (mild or moderate), 20% report any degree of hearing deficit and all the pts report normal social activities. Conclusions: Although this is a preliminary analysis, with a short follow-up, the majority of the pts report good voice and swallowing function and most of them are socially integrated. Hearing problems were more reported then acute ototoxicity during chemo-radiation treatment. Accrual continues with video fluoroscopy analysis. No significant financial relationships to disclose.
‘Big Five’ of sports medicine: preparation, teamwork, passion, mentorship and collaboration
Authors: Jonathan A Drezner
Journal: British Journal of Sports Medicine (2016)

As BJSM Senior Associate Editor for Sports Cardiology since 2008, I have witnessed our discipline of sports medicine come of age. BJSM 's goal of helping to unite our field is coming into sight, and the world of sports medicine has never felt closer. As I write this, 23 BJSM affiliated societies from 16 countries are celebrated on a prominent international stage. Collaboration among countries has become both the norm and the foundation of new learning, strategic partnerships and key initiatives for athlete safety and health promotion.

The power of international collaboration was on prominent display at the recent South African Sports Medicine Association (SASMA) conference where Congress Convenor Dr Jon Patricios and SASMA President-elect Dr Phatho Zondi combined gracious South African hospitality with a premier scientific programme to inspire sports medicine professionals at every level.

I was honoured to participate in the SASMA congress and am grateful for my entire experience; undoubtedly a professional highlight and …
Flaxseed oil is the major component of flaxseed that increases the effectiveness of tamoxifen in reducing established MCF-7 tumor growth in ovariectomized nude mice
Authors: Jianmin Chen, Jasdeep Saggar, Mary Webster, Lilian Thompson
Journal: Cancer Research (2007)

1003  Flaxseed (FS) contains high amounts of the phytoestrogen lignan (secoisolariciresinol diglycoside, SDG), and n-3 fatty acid -rich oil (flaxseed oil, FO), both of which are hypothesized to have anticancer effects. Our previous studies have demonstrated that 10% FS diet attenuates the growth of human breast cancer (MCF-7) xenografts treated by tamoxifen (TAM) in ovariectomized nude mice. To elucidate which component (SDG or FO) is responsible for the inhibitory effect of FS when combined with TAM, and whether the SDG-rich hull (FH) or oil- rich cotyledon (FC) fractions of FS have equivalent effectiveness as the pure SDG or FO, this study was designed to determine the effect of pure SDG, FO, or their combination (SDG+FO), as well as FS fractions, FH, FC, or their combination (FH+FC), on the growth of established MCF-7 xenografts in ovariectomized athymic mice treated with TAM. The doses of SDG, FO, FH and FC were equivalent to their amounts in 10% FS diet. The mice were injected with MCF-7 cells, implanted subcutaneously with a 17-b estradiol (E2) pellet, and fed the basal diet (BD). When the palpable tumors reached 30 mm2 size, the existing E2 pellet was removed and all mice were implanted a TAM pellet (5mg 60 day release), except the negative control (NC) and the positive control (PC), which was implanted with a placebo or new E2 pellet, respectively. All treatments were given for 8 weeks. Palpable tumor size increased by 138% in the PC group but decreased by 37% in the NC group (p
Effector and regulatory lymphocytes in asthmatic pregnant women
Authors: Lilla Tamási, Anikό Bohács, Άron Cseh, Noémi Eszes, János Rigό, Veronika Müller, Barna Vásárhelyi, György Losonczy
Journal: European Respiratory Journal (2011)

Asthma is one of the most common diseases that may complicate pregnancy. Asthma and pregnancy show bidirectional interactions with unknown immunological mechanisms. The aim of this study was to evaluate CD4+ regulatory T (Treg), natural killer (NK), NKT, invariant natural killer (iNKT), memory and naive CD4+T lymphocytes in mild to moderate partially or well controlled persistant asthmatic pregnant patients.

The prevalence of lymphocyte subsets was identified by cell surface markers and intracellular FoxP3 staining, in healthy non-pregnant (HNP; N=15), healthy pregnant (HP; N=33), asthmatic non-pregnant (ANP; N=62) and asthmatic pregnant (AP; N=61) women. Data are given in median and quartiles.

Treg cell prevalence was higher in HP than in HNP subjects (7.82 (5.27-10.24) vs. 4.88 (1.82-6.19), respectively; p=0.0052) and showed a positive correlation with fetal birth weight (p=0.02), which was blunted in AP group. AP patients had lower Treg (5.53 (2.45-7.83)) and higher iNKT (0.04 (0.01-0.18)) cell numbers than HP subjects (7.82 (5.27-10.24) and 0.01 (0.0-0.03), respectively; all p<0.05) that might suggest compromised pregnancy induced immunotolerance caused by allergic inflammation. However, lower effector/memory and higher naive T cell prevalence observed in AP (30.60 (24.42-44.18) and 57.24 (46.34-67.06), respectively) than in ANP group (43.11 (32.52-55.38) and 48.18 (38.07-58.62), respectively) suggested immunosuppression exerted by pregnancy on asthma.

Pregnancy induced Treg cell proliferation is absent in asthmatic pregnancy that may interfere with normal intrauterine growth. However, pregnancy induced inhibition of asthmatic immune responses can also be detected in uncomplicated asthmatic pregnancy.
Epidermal growth factor receptor (<i>EGFR</i>) mutations in breast and cervical cancer
Authors: M. S. Park, K. Puttaswamy, Z. Gombos, A. Geza, M. S. Brose
Journal: Journal of Clinical Oncology (2006)

20101 Background: EGFR is a tyrosine kinase receptor in the HER family which is widely expressed in a number of epithelial tumors and is believed to play a key role in cell proliferation. Molecular analysis of the EGFR gene in patients with non-small-cell lung cancer have identified a distinct subset of tumors that possess specific point mutations in the tyrosine kinase region of the EGFR gene, which correlate to response to tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. Clinical trials involving TKIs are currently under way for patients with breast and cervical cancer. While responses thus far may have been modest it is unclear whether specific EGFR mutations are present in breast and cervical cancers which identify patients with improved prognosis and better response to therapy in these cancers. Using clinical samples with 5 years of follow-up clinical data, we have set out to determine whether EGFR mutations exist in breast and cervical cancers, and how these mutations, if any, correlate with the clinical data. Methods: We plan to perform sequence analysis of the tyrosine kinase domain of the EGFR gene (exons 18–24) in 50 archival breast and 44 cervical cancer specimens using PCR amplification and sequencing of genomic DNA. Clinical information has been extracted from patient charts on samples and will be correlated with the presence of any EGFR mutations identified. Results: To date we have collected 50 breast and 44 cervical tumor blocks and have isolated genomic DNA from the specimens. Sequencing for point mutations in exons 18–24 is underway. Clinical data on the cervical cancer specimens revealed a mean age at diagnosis of 48.2 years, tumor grades that were mostly intermediate (50%) and high (45%), and all FICO stages at diagnosis (43% stage I, 30% stage II, 5% stage III, 5% stage IV). In addition the rate of recurrence was 32%, and survival rate was 82% with an average time of follow-up for the set of 4.9 years. Conclusions: Our data will further elucidate the role of point mutations in EGFR gene in breast and cervical cancer prognosis and response to therapy, and will complement data currently being collected in clinical trials using TKIs. No significant financial relationships to disclose.
Anthramine Carcinogenesis in the Skin of Rats. II. The Pilosebaceous Apparatus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Richard L. Dobson, M.D.
Journal: JNCI Journal of the National Cancer Institute (1963)

Repeated application of 2-anthramine to the skin of rats resulted in the formation of undifferentiated nests of basal cells derived from hair follicles. Basal cell epitheliomas arising from these nests proliferated only if the surrounding connective tissue was abnormal. Eventually, tumors resulted, with both epithelial and stromal components resembling a part or parts of the hair follicle. Cells derived from the hair follicle also produced squamous cell carcinomas. Similar nests of cells arose from sebaceous glands, but these cells appeared incapable of hair-follicle differentiation, although sebaceous gland tumors, undifferentiated basal cell epitheliomas, and squamous cell carcinomas were seen. The results suggest stromal control over the growth of cells derived from hair follicles. Sebaceous gland cells derived from a localized area of the hair follicle appeared to have inherent control and thus could not produce follicle-like structures under the influence of connective-tissue organizers.