tbuckley/cabot-search huggingface dataset:
Histogenesis of Symmetrical 1,2-Dimethylhydrazine-Induced Neoplasms of the Colon in the Mouse 2
Authors: William W. L. Chang
Journal: JNCI Journal of the National Cancer Institute (1978)

CF-1 female adult mice were given weekly sc injections of 20 mg symmetrical 1,2-dimethylhydrazine (DMH)·;2HCl/kg body weight and killed at various intervals after commencement of the injection. [3H]thymidine (TdR) was given before the animals were killed. The histogenesis of colon neoplasms was investigated by means of auto radiographs prepared from sections of Epon-embedded descending colon, which were stained with periodic acid-Schiff reaction and iron hematoxylin. By 9 weeks after initiation of DMH treatment, the distal 5 cm of the colon became enlarged, the mucosa thickened, and the crypts were elongated and hyperplastic. In the hyperplastic crypts, the number of proliferating cells increased, but the distribution of these cells followed a previously discussed slow cut-off model of Cairnie et al. as for the normal crypts. Differentiation and transformation of epithelial cells occurred, but somewhat aberrantly. Hyperplasia of the crypts occurred diffusely, but neoplastic lesions that began to appear by 9 weeks after the initial treatment were isolated. An isolated crypt from which a neoplasm developed was first repopulated by what appeared to be altered, undifferentiated “stem” cells. These cells did not differentiate, continued to divide, and eventually upon migration accumulated in the upper part of the crypts, where an earliest identifiable neoplastic lesion was observed. Once such a lesion was formed, it expanded in various directions, depending on the local environments, and formed a polypoid or discoid lesion. The biologic behavior of the neoplasm seemed to be determined by the downward progression of its leading edge. When it penetrated the muscularis mucosae, the neoplasm became highly invasive. In the murine model, the invasive adenocarcinomas were observed by 26 weeks after commencement of DMH treatment.
Limited-sampling models for irinotecan pharmacokinetics-pharmacodynamics: prediction of biliary index and intestinal toxicity.
Authors: R Mick, E Gupta, E E Vokes, M J Ratain
Journal: Journal of Clinical Oncology (1996)

PURPOSE To construct limited-sampling models (LSMs) for irinotecan (CPT-11) pharmacokinetic (PK) measures. MATERIALS AND METHODS The recommended phase II dose of weekly CPT-11 administered as a 90-minute infusion is 145 mg/m2 with granulocyte colony-stimulating factor (G-CSF) and maximal antidiarrheal support. Diarrhea is the dose-limiting toxicity. Previously, we demonstrated a highly significant correlation between severity of diarrhea and biliary index (BI), the estimated biliary exposure of SN-38. BI was the product of total CPT-11 area under the concentration-time curve (AUC) and the relative area ratio of SN-38 to SN-38 glucuronide (SN-38G). At 145 mg/m2, PK data were available for 40 patients; 36 were also assessable for intestinal toxicity. Total plasma concentrations of CPT-11, SN-38, and SN-38G from 1.0 to 11.5 hours from the start of the infusion were evaluated. CPT-11 concentration at each time point, t, is denoted by CPT-11t. LSMs were constructed by stepwise linear regression, on a training set (n = 25), and were validated on a test set (n = 15). RESULTS LSMs for CPT-11, SN-38, and SN-38G AUCs displayed excellent fit to the training set (R2 = .87, 0.75, and .98, respectively). AUCCPT-11 = 5.25 x CPT-11(3.0) + 20.60 x CPT-11(11.5) + 1,520.53; AUCSN-38 = 5.38 x SN-38(3.5) + 33.61 x SN-38(11.5) - 7.73; and AUCSN-38G = 10.73 x SN-38G9.5 + 20.66 x SN-38G11.5 + 142.69. BI at each time point (denoted BIt) was calculated as CPT-11t x (SN-38t/SN-38Gt). Several promising LSMs were defined by BI3.5 paired with BI7.5 (R2 = .63) or BI9.5 (R2 = .76), or BI5.5 paired with BI9.5 (R2 = .76). Predicted BI from each model (categorized into low, intermediate, or high) accurately predicted observed intestinal toxicity grade (P &lt; or = .005). CONCLUSION These LSMs appear to accurately predict PK parameters of CPT-11. Notably, BI, predicted from several LSMs, accurately predicted intestinal toxicity and thus may be useful for future trials that use adaptive control with feedback.
Breast cancer subtypes based on ER/PR and HER2 expression: A population-based experience
Authors: A. A. Onitilo, J. Engel, R. T. Greenlee, B. Mukesh
Journal: Journal of Clinical Oncology (2008)

22181 Background: Immunohistochemical (IHC) classification for breast cancer subtypes correlates with intrinsic gene expression microarray categorization: estrogen/progesterone receptor positive, human epidermal growth factor receptor 2 positive (ER/PR+, HER2+) with Luminal B; ER/PR+, HER2− with Luminal A; ER/PR−, HER2+; and ER/PR−, HER2− with triple negative/basal-like tumors. Methods: This is a retrospective study of 1,134 invasive breast cancer subjects from Marshfield Clinic/St Joseph's Hospital Cancer Registry (January 1, 1998 to June 30, 2005). Four breast cancer subtypes were identified based on IHC expression of the ER/PR and HER2 proteins: ER/PR+, HER2+; ER/PR+, HER2−; ER/PR−, HER2+ and ER/PR−, HER2−. Clinical outcome and survival of the different subtypes were compared. Results: One hundred sixteen subjects (10.2%) were ER/PR+, HER2+; 781 (68.9%) were ER/PR+, HER2−; 85 (7.5%) were ER/PR−, HER2+; and 152 (13.4%) were ER/PR−, HER2−. Triple negative subtype had worse overall survival, (Hazard ratio: 1.8, 95% CI: 1.01, 3.0) and disease-free survival (Hazard ratio: 1.8, 95% CI: 1.2, 3.0) compared to ER/PR+, HER2− after adjusting for age, stage, histological grade, chemotherapy, node and menopausal status. ER/PR−, HER2+ subtype (Hazard ratio: 2.0, 95% CI: 1.2, 3.5) had shorter disease-free survival compared to ER/PR+, HER2− subtype. In the ER/PR+, HER2− subtype chemotherapy conferred significant overall and disease-free survival advantage. Conclusions: Triple-negative and ER/PR−, HER2+ subtypes have poorer clinical, pathologic, and molecular prognoses. Targeted therapies for triple negative breast cancer are lacking. Further confirmatory studies are necessary to refine IHC classification as it is clinically-used, therapeutically informative, and prognostic as well as somewhat predictive. No significant financial relationships to disclose.
Residual cancer burden (RCB) in breast cancer patients treated with taxane- and anthracycline-based neoadjuvant chemotherapy: The effect of race.
Authors: M. Chavez-Mac Gregor, R. Hubbard, F. Meric-Bernstam, S. S. Shinde, J. K. Litton, W. A. Woodward, V. Valero, G. N. Hortobagyi, W. F. Symmans, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2010)

607 Background: Race is associated with outcomes in breast cancer patients. Differences in tumor biology, leading to variations in treatment response may play a significant role. RCB index is an independent prognostic factor after NST. In this retrospective study we sought to evaluate the prognostic effect of RBC according to race. Methods: 567 female patients with primary breast cancer treated with NST with weekly paclitaxel followed by FAC at M. D. Anderson Cancer Center between 1998 and 2008 were included. Patients had available post-treatment resection pathology materials from clinical trial 98-240 and protocol LAB-402. No patients received trastuzumab therapy. RCB index was determined by dedicated breast pathologists. Primary outcome was the association of race and RCB. Kaplan-Meier method was used to evaluate the effect of RCB according to race for OS and DFS; groups were compared using log-rank test. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with RCB. Results: Median follow up was 64 months (5-164). 390 (68.8%) patients were white, 67 (11.8%) black, 81 (14.3%) Hispanic, and 29 (5.1%) from other race. No difference was seen in the distribution of hormone receptor+, HER2+ and triple negative tumors (p = 0.656) or RCB category (p = 0.410) according to race. RCB was associated with OS, in white (p < 0.001), black (p = 0.015) and other race (p = 0.020) patients but not in Hispanics (p = 0.646). Similar results were seen for DFS. In a multivariable model, RCB2 (HR: 5.6; 95%CI 2.34-13.36) and RCB3 (HR: 15.28; 95% CI 6.34-36.8) were associated with worse survival. Compared to whites, black patients had worse outcomes (HR for OS: 1.89; 95% CI 1.21-3.21, HR for DFS: 2.17; 95% CI 1.37-3.44). Hispanic patients tended to have improved outcomes (HR for OS: 0.473; 95% CI 0.202-1.10, HR for DFS: 0.677; 95%CI 0.365-1.25) but statistical significance was not reached. Conclusions: In this cohort of patients a similar distribution of RCB was seen in all four race groups considered. The association of RCB and outcome was present in all analyzed racial groups except Hispanics. This is the first study analyzing the association between race and RCB. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nuvera Biosciences Nuvera Biosciences
Simultaneous 68Ga-PSMA HBED-CC PET/MRI Improves the Localization of Primary Prostate Cancer
Authors: Matthias Eiber, Gregor Weirich, Konstantin Holzapfel, Michael Souvatzoglou, Bernhard Haller, Isabel Rauscher, Ambros J. Beer, Hans-Jürgen Wester, Juergen Gschwend, Markus Schwaiger, Tobias Maurer
Journal: European Urology (2016)
Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy
Authors: Christina Pfirschke, Camilla Engblom, Steffen Rickelt, Virna Cortez-Retamozo, Christopher Garris, Ferdinando Pucci, Takahiro Yamazaki, Vichnou Poirier-Colame, Andita Newton, Younes Redouane, Yi-Jang Lin, Gregory Wojtkiewicz, Yoshiko Iwamoto, Mari Mino-Kenudson, Tiffany G. Huynh, Richard O. Hynes, Gordon J. Freeman, Guido Kroemer, Laurence Zitvogel, Ralph Weissleder, Mikael J. Pittet
Journal: Immunity (2016)
Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys.
Authors: A Debska-Slizien, P Ho, R Drangova, A D Baines
Journal: Journal of the American Society of Nephrology (1994)

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)
Unexpected toxicity (UT) and opportunistic infections (OI) after rituximab-containing therapy for non-Hodgkin's lymphoma (NHL)
Authors: M. Hentrich, A. Gerl, L. Lutz, M. Karthaus, X. Schiel
Journal: Journal of Clinical Oncology (2009)

e19546 Background: Rituximab (R) is increasingly used for the treatment of B-NHL. Most adverse events are mild to moderate. In rare cases, however, R may be associated with severe UT and OI. Methods: The records of consecutive pts treated at 2 institutions from 01/06 to 12/08 with R-containing chemotherapy or R-maintenance therapy (R-M) for NHL were analyzed for severe UT and OI. UT was considered as related to R if it could not be explained otherwise. Results: 99 pts were included in the cohort study. Pts received a median of 6 cycles (range 1 - 18) of R. A total of 517 cycles of R were evaluable for OI or UT. 7 of 99 pts (7%) (2 females, 5 males) with a median age of 69.5 yrs (range 41–76) experienced UT (n=4) or OI (n=3). UT consisted of interstitial pneumonitis (IP) in 2 pts after 8 and 6 cycles of R-CHOP for diffuse large cell lymphoma (DLCL), a case of congestive heart failure (NYHA III°) after 6x R-CHOP + 2x R-M for follicular lymphoma (FL) and a case of grade 4 pancytopenia lasting for 22 days following 2x R-FC for chronic lymphocytic leukemia. IP completely resolved after initiation of prednisone (n=1) or under empiric antimicrobial therapy (n=1). Congestive heart failure improved under appropriate therapy and the pt received 2 more cycles of R-M. Pancytopenia slowly recovered under therapy with G-CSF, R was terminated. OI consisted of pneumocystis jirovecii pneumonia after 5x R-CHOP-14 for DLCL, Epstein-Barr-virus (EBV)-associated hepatitis after 5x R-CHOP-21 for relapsed FL and generalized herpes zoster following 6x R-bendamustine (RB) + 1x R-M for recurrent BALT-lymphoma. R was restarted in the latter 2 pts. Infections resolved under antimicrobial therapy. EBV-hepatitis improved spontaneously. Moreover, 2 pts were transferred to us for therapy of enterovirus-induced encephalitis after 6x R-CHOP-21 + 2x R-M for FL (n=1) and cerebral toxoplasmosis in a pt heavily pretreated with R-containing therapy for relapsed mantle cell lymphoma (n=1). Conclusions: Severe UT and OI are rare but potentially fatal complications. Awareness of UT/OI, rapid diagnostic proceedings and, whenever possible, initiation of therapy are essential. In selected cases reexposure of R may be feasible. No significant financial relationships to disclose.
Ten-year outcome of patients with advanced epithelial ovarian carcinoma treated with cisplatin-based multimodality therapy.
Authors: P J Hoskins, S E O'Reilly, K D Swenerton, J J Spinelli, R N Fairey, J L Benedet
Journal: Journal of Clinical Oncology (1992)

At the end of the 1970s it was thought that advanced epithelial ovarian cancer (EOC) could be cured by multimodality treatment using surgery, cisplatin-based combination chemotherapy, and radiotherapy (RT). Such multimodality treatment was used as standard therapy at our institution. Our long-term results are reviewed.One hundred ninety-five previously untreated patients with stage III or IV EOC were treated between April 1979 and December 1982. All patients were to have debulking surgery, when feasible, followed by the administration of doxorubicin and cisplatin at 50 mg/m2 every 3 weeks until a total dose of doxorubicin of 450 mg/m2 had been reached. RT was used in addition in patients with disease remaining after the chemotherapy. Maintenance chemotherapy with oral cyclophosphamide and hexamethylmelamine (altretamine) was administered to patients who did not have a documented histologic complete remission.The 10-year overall and failure-free survivals were 4% and 8%, respectively. The median overall survival was 2 years. The achievement of a histologic complete response (n = 32) did not equate to cure because 20 (63%) of the patients eventually relapsed. Multivariate analysis identified residual disease of greater or less than 2 cm as the only independent prognostic factor.Our multimodality treatment program was noncurative for the majority of the patients. Innovative therapies are needed before we can hope to cure such disease.
Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia
Authors: A. Lal, P. Kumar, Y. Bhurgri, N. Rizvi, A. J. Shaikh, S. Adil, N. Masood, M. Virwani
Journal: Journal of Clinical Oncology (2009)

e20716 Background: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. Methods: A cross-sectional descriptive study was conducted on patients, &gt;18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. Results: A total of 80 patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD ±16.6; range 18–79) years. Sixty eight patients (86%) were &lt; 65 years, 50% were &lt; 50 years. Overall, in hospital mortality was 11%; 4% for patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD ±3.8; range 2–17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer and &gt; three times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death. Conclusions: The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further. No significant financial relationships to disclose.
Immunization of indolent non-Hodgkin’s lymphoma patients with autologous monocyte-derived dendritic cells loaded with heat shocked and killed autologous tumor cells: A phase I study
Authors: M. A. Di Nicola, C. Carlo-Stella, R. Zappasodi, L. Passoni, D. Liliana, M. Magni, P. Matteucci, R. Mortarini, A. Anichini, A. M. Gianni
Journal: Journal of Clinical Oncology (2007)

3006 Background: To evaluate the safety and tolerability of vaccination with DCs loaded with killed tumor cells, 18 patients with measurable relapse/refractory follicular (12) and lymphoplasmocytoid (6) lymphoma have been enrolled in a phase I study. Methods: Each patient received at 2-weekly intervals 4 SC injections of 50x10e6 tumor-loaded DCs. Immature DCs were generated by 5-days culture of autologous monocytes in the presence of IL-4 and GM-CSF. Autologous CD19+ tumor cells, harvested from lymph nodes (12) and/or peripheral blood (6), were heat shocked and then irradiated by UVC. DCs were loaded for 48 hrs with killed tumor cells and then were cultured for 12 hrs in the presence of TNF-a. Median prior number of treatment regimens was 2 (range 1–5) comprising 4 patients treated with high-dose chemotherapy. The vaccination was started at least 6-months after the last chemotherapy treatment. Results: All patients were evaluable for toxicity and for efficacy with a median follow-up of 30.5 months (range 18–45 months). Overall, vaccinations were well tolerated and no autoimmune reactions were observed. Mild erythema in the site of injection developed in the majority of patients (12/18), but only in 2 cases induration and extended erythema was observed. Six of 18 patients had objective responses. Three patients had partial responses (PR). One is still in PR and the others have a PR lasting 7 and 15 months, respectively. Three patients had complete remission (CR) and are are still in CR with a mean CR duration of 17 months. The remaining 12 patients had stable disease (8) or progressive disease (4). In the patients in PR, a significant increase of anti autologous tumor-specific T cells, evaluated by ELISPOT assay for IFN-γ, was observed in the post-vaccination lymph nodes, compared to the tissue sample taken before vaccination. In addition, in the responding patients a significant reduction in peripheral blood of FoxP3+ regulatory T cells was observed. Conclusion: The injection of DCs loaded with killed tumor cells is a well-tolerated procedure achieving clinical and immunological responses also in the presence of significant tumor burden. No significant financial relationships to disclose.
Prognostic factors of oligodendrogliomas
Authors: M. Frenay, A. Ramaioli, D. Fontaine, V. Bourg, F. Vandenbos, C. Lebrun
Journal: Journal of Clinical Oncology (2004)

1560 Background: Oligodendrogliomas (OG) have better prognosis than other glial tumors, maybe due to a better response to chemotherapy and molecular profile, as 1p/19q deletions. Methods: We evaluated 100 consecutive patients, representing 9% of patients with PBT in our database, with newly diagnosed OG from 1995 to 2002, in order to identifie prognostic factors. Three subgroups of patients were defined: group A: low grade (LOG) or grade II; group B : LOG with malignant transformation during the follow-up or Transformed AOG (TOG); group C : de novo anaplastic (AOG) or grade III. The prognostic significance of individual factors was evaluated by comparing the 2, 5 and 10-year survival rates. Results: Patients characteristics were: 66 men, 34 women; median follow-up : 4 years; mean age at the first symptom :46 years; mean age at diagnosis: 46.7 years. The initial presenting symptom was: partial seizures, neurological deficit, headache or cognitive changes. Sixty patients had gadolinium enhancement (A :15%, C :90%). After histological diagnosis, symptomatic patients had a second line of treatment (chemotherapy or radiotherapy). Mean time for transformation for group B was 72 months with a median survival of 86 months (14 months after malignant transformation). Survivals at 2, 5 and 10 years were: A: 88%, 88%, 85%; B:79%, 64%, 42%; C :43%, 16%, 15% (p<0.0001). No difference in survival was observed between groups B and C after the diagnosis of malignant transformation (p=0.57). Using univariate analysis, age < 40years (p<0.0003), lack of contrast enhancement at diagnosis (p<0.00001) and epilepsy (p<0.007) were correlated with good prognosis. Complete surgery, compared partial resection or biopsy, did not influence survival time. In multivariate analysis, the strongest prognostic factor was lack of contrast enhancement (RR=3.4), followed by revealing symptom (RR=1.27) and age <40 years (RR=1.04). Relative risk for the grade II was age < 40years: 1.04; epilepsy: 1.6; enhancement: 2.66. For the grade III patients, only age remained significant (RR=1.02, p<0.03). Conclusions: OG have a good prognosis. Whatever the grade considered, contrast enhancement is the strongest prognostic factor. No significant financial relationships to disclose.
Parental nutrition: is it oncologically logical?
Authors: R L Koretz
Journal: Journal of Clinical Oncology (1984)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1984.2.5.534 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 6427418 Parental nutrition: is it oncologically logical? R L KoretzxR L KoretzSearch for articles by this author https://doi.org/10.1200/JCO.1984.2.5.534 First Page PDF © 1984 by American Society of Clinical Oncology