bluuebunny/crossref_metadata_2025_split huggingface dataset:
An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane
Authors: Buzdar Aman U. , Robertson John F. R. , Eiermann Wolfgang , Nabholtz Jean‐Marc 
Published: October 2002

AbstractBACKGROUNDThe newer generation, nonsteroidal aromatase inhibitors (AIs) anastrozole and letrozole have shown superior efficacy compared with tamoxifen as first‐line treatments and compared with megestrol acetate as second‐line therapy in postmenopausal women with advanced breast carcinoma. In an open‐label, Phase II trial, it was reported that exemestane showed numerical superiority compared with tamoxifen for objective response and clinical benefit. Because these agents ultimately may be administered for periods of up to 5 years in the adjuvant setting, it is of increasing importance to assess their tolerability and pharmacologic profiles.METHODSIn the absence of data from direct clinical comparisons, the published literature was reviewed for the clinical pharmacology, pharmacokinetic characteristics, and selectivity profiles of anastrozole, letrozole, and exemestane.RESULTSAt clinically administered doses, the plasma half‐lives of anastrozole (1 mg once daily), letrozole (2.5 mg once daily), and exemestane (25 mg once daily) were 41–48 hours, 2–4 days, and 27 hours, respectively. The time to steady‐state plasma levels was 7 days for both anastrozole and exemestane and 60 days for letrozole. Androgenic side effects have been reported only with exemestane. Anastrozole treatment had no impact on plasma lipid levels, whereas both letrozole and exemestane had an unfavorable effect on plasma lipid levels. In indirect comparisons, anastrozole showed the highest degree of selectivity compared with letrozole and exemestane in terms of a lack of effect on adrenosteroidogenesis.CONCLUSIONSAll three AIs demonstrated clinical efficacy over preexisting treatments. However, there were differences in terms of pharmacokinetics and effects on lipid levels and adrenosteroidogenesis. The long‐term clinical significance of these differences remains to be elucidated. Cancer 2002;95:2006–16. © 2002 American Cancer Society.DOI 10.1002/cncr.10908
Gliomatosis cerebri
Authors: Elshaikh Mohamed A. , Stevens Glen H.J. , Peereboom David M. , Cohen Bruce H. , Prayson Richard A. , Lee Shih‐Yuan , Barnett Gene H. , Suh John H. 
Published: October 2002

AbstractBACKGROUNDGliomatosis cerebri (GC) is a rare primary brain tumor characterized by proliferation of neoplastic glial cells that typically involve multiple brain areas, with preservation of brain structures and sparing of neurons. The optimal therapeutic strategy is not well established. The impact of radiotherapy on survival in patients with GC remains undefined.METHODSBetween 1980 and 2001, 12 patients with GC were identified, representing less than 1% of all patients with primary brain neoplasms treated at the Cleveland Clinic.RESULTSAll 12 patients had brain biopsies between March 1986 and July 2001 (seven males, five females, with a median age of 53 years [range, 13–85 years]). Median Karnofsky performance status at the time of presentation was 70 (range, 40–90). Eight patients had low‐grade gliomas and four patients had anaplastic astrocytomas. Eight patients received radiation treatment to the brain as the only treatment, and four received neither radiation nor chemotherapy. The median dose of megavoltage radiation was 55.4 Gy (range, 45–61.2 Gy). Of the eight patients who received brain radiotherapy, the clinical and radiologic follow‐up findings improved in three patients, stabilized in three patients, and worsened in two patients. Median follow‐up was 10.3 months (range, 1–55 months). The median survival for the eight patients who received brain radiotherapy was 11.4 months. The one– and two‐year survival rates were 45% and 30%, respectively. Two of the eight patients who received radiotherapy were alive at the time of writing. The four patients who did not receive radiotherapy died of the disease at 0.6, 1.0, 1.9, and 2.4 months after diagnosis.CONCLUSIONSGliomatosis cerebri is associated with poor survival. Although brain radiotherapy controlled or stabilized disease progression in most patients, the overall survival after brain radiotherapy alone was not satisfactory. More aggressive therapy may be needed. Cancer 2002;95:2027–31. © 2002 American Cancer Society.DOI 10.1002/cncr.10909
Comparison of selection strategies for genetic testing of patients with hereditary nonpolyposis colorectal carcinoma
Authors: Reyes Carolina M. , Allen Brian A. , Terdiman Jonathan P. , Wilson Leslie S. 
Published: October 2002

AbstractBACKGROUNDMolecular testing for hereditary nonpolyposis colorectal carcinoma (HNPCC) is becoming standard care and it is cost‐effective compared with no genetic testing. However, the best strategy for detection of HNPCC gene carriers is unknown.METHODSWe use a decision analytic model to evaluate the effectiveness and incremental cost‐effectiveness of four commonly used testing strategies to detect HNPCC gene carriers. The model starts with a population of colorectal carcinoma (CRC) patients and measures costs, the number of gene carriers detected, and incremental costs per gene carrier detected.RESULTSWe found that germline testing on only those CRC probands who meet the Amsterdam criteria detects the fewest gene carriers and has the lowest cost whereas tumor microsatellite instability (MSI) testing of all CRC patients and families has the highest cost and detects the most gene carriers. When cost‐effectiveness is considered, the mixed strategy (MSH2 and MLH1 testing on those who meet the Amsterdam criteria and germline testing for the remainder who meet less stringent modified criteria and are MSI‐High) seems superior. The mixed strategy detects 59.6 mutation carriers per 1000 CRC cases and costs much less than the test all strategy, which has an incremental cost‐effectiveness of $51,151. The mixed strategy often other strategies and when compared to the Amsterdam strategy, has a cost‐effectiveness of only $6441 per gene carrier detected.CONCLUSIONSIt is not very effective to limit genetic testing to only individuals who meet the Amsterdam criteria, as many gene carriers are missed. However, testing all CRC patients for tumor MSI‐H, although effective, may be prohibitively expensive. A mixed strategy is the more cost‐effective approach. Cancer 2002;95:1848–56. © 2002 American Cancer Society.DOI 10.1002/cncr.10910
Telomerase activity in Stage II colorectal carcinoma
Authors: Kawanishi‐Tabata Rika , Lopez Francisco , Fratantonio Sam , Kim Nam , Goldblum John , Tubbs Raymond , Elson Paul , Lavery Ian , Bukowski Ronald M. , Ganapathi Ram , Ganapathi Mahrukh K. 
Published: October 2002

AbstractBACKGROUNDTelomerase is a ribonucleoprotein polymerase that adds telomeric repeats to chromosome ends. This enzyme is deficient in the majority of normal somatic cells, but often is reactivated during tumorigenesis. In the current study, the authors examined telomerase activity in human American Joint Committee on Cancer Stage II colorectal carcinomas and correlated it with traditional prognostic indicators and disease outcome.METHODSThe telomerase repeat amplification protocol (TRAP) was employed to determine telomerase activity in 122 surgical specimens (from 77 male and 45 female patients) of human Stage II colorectal carcinoma. The primary site of the tumor was the colon in 52 cases and the rectum in 70 cases. Telomerase activity was correlated with traditional prognostic indicators such as gender, age, T classification, tumor size, tumor grade, and disease outcome (overall survival and disease‐free survival). The Median follow‐up for patients who still were alive was 5.8 years.RESULTSTelomerase activity was detected in 80% of the tumors (98 of 122 tumors). Telomerase‐positive patients differed from telomerase‐negative patients in that they tended to be female (41% vs. 21%; P = 0.1), presented with primary tumors of the colon more frequently (49% vs. 17%; P = 0.01), and had a higher T classification (T4) (62% vs. 38%; P = 0.04). Univariate and multivariate analyses demonstrated a correlation between telomerase activity and disease‐free survival (P = 0.05).CONCLUSIONSAlthough a large percentage of Stage II colorectal carcinoma samples were positive for telomerase activity, the prognosis for patients with telomerase‐negative tumors was found to be worse than that for patients with telomerase‐positive tumors. Cancer 2002;95:1834–9. © 2002 American Cancer Society.DOI 10.1002/cncr.10911
Estrogen replacement therapy for menopausal women with a history of breast carcinoma
Authors: Vassilopoulou‐Sellin Rena , Cohen Deborah S. , Hortobagyi Gabriel N. , Klein Mary Jean , McNeese Marsha , Singletary S. Eva , Smith Terry L. , Theriault Richard L. 
Published: October 2002

AbstractBACKGROUNDWomen with a history of breast carcinoma generally have been advised to avoid estrogen replacement therapy (ERT). The validity of this approach has been scrutinized and debated in recent years, and reassessment through appropriate clinical trials has been suggested.METHODSThe authors conducted a prospective clinical trial to assess the safety and efficacy of prolonged ERT in a group of menopausal women with localized (Stage I or Stage II) breast carcinoma and a minimum disease free interval of 2 years if estrogen receptor (ER) was negative or 10 years if ER status was unknown. For 5 years, the authors followed 77 trial participants and 222 other women with clinical and prognostic characteristics comparable to those of the trial participants. Overall, 56 women were on ERT, and 243 women were not on ERT. The association of ERT with skeletal and lipid changes was assessed in the randomized trial participants. The effect of ERT on the development of recurrent or new breast carcinoma and other carcinomas was analyzed both in the trial participants and in the overall group.RESULTSPatient and disease characteristics, such as tumor size, number of lymph nodes involved, ER status, menopausal status, and disease free interval were comparable for women who were on ERT and women who were not on ERT. These same parameters also were comparable for women who joined the trial and women who did not. ERT use was associated with modest lipid and skeletal benefits. The introduction of ERT did not compromise disease free survival. Two of 56 women on ERT (3.6%) developed a contralateral, new breast carcinoma. In the group that was not on ERT, 33 of 243 women (13.5%) developed new or recurrent breast carcinoma. There were no differences in the development of other carcinomas with respect to ERT.CONCLUSIONSERT did not compromise disease free survival in select patients who were treated previously for localized breast carcinoma. Larger scale randomized trials are needed to confirm these findings. Cancer 2002;95:1817–26. © 2002 American Cancer Society.DOI 10.1002/cncr.10913
Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia
Authors: Selleri Carmine , Maciejewski Jaroslaw P. , Catalano Lucio , Ricci Patrizia , Andretta Claudia , Luciano Luigiana , Rotoli Bruno 
Published: October 2002

AbstractBACKGROUNDImmunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure.METHODSUsing flow cytometry, we studied Fas‐receptor (Fas‐R), Fas‐ligand (Fas‐L), and interferon‐γ (IFN‐γ) expression in CD34+ cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long‐term cultures, the effects of Fas triggering, IFN‐γ blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony‐forming cells [CFC]) were determined. The effects of CsA at daily doses of 1–3 mg/kg for at least 3 months in HMDS patients were also studied.RESULTSIn basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN‐γ–expressing CD4+ cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas‐L expression was only borderline elevated in CD3+ MDS cells. Increased numbers of CD34+ cells expressing Fas‐R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas‐L–mediated inhibition and the blockade of IFN‐γ improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN‐γ–expressing CD4+ cells, but not Fas‐L production. These effects were associated with increased colony formation. Similar to IFN‐γblockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients.CONCLUSIONSIncreased frequency of IFN‐γ producing CD4+ cells supports the involvement of lymphocyte‐mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN‐γ production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients. Cancer 2002;95:1911–22. © 2002 American Cancer Society.DOI 10.1002/cncr.10915
Expression of matrix metalloproteinase 1, matrix metalloproteinase 2, and matrix metalloproteinase 9 in carcinoma of the head and neck
Authors: Franchi Alessandro , Santucci Marco , Masini Emanuela , Sardi Iacopo , Paglierani Milena , Gallo Oreste 
Published: October 2002

AbstractBACKGROUNDNumerous reports have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). In this study, the authors examined whether the expression of MMPs in HNSCC is correlated with other steps involved in tumor growth and metastasis, like angiogenesis, activation the nitric oxide (NO) pathway, and alteration of the p53 tumor suppressor gene.METHODSMMP‐1, MMP‐2, and MMP‐9 expression levels were examined immunohistochemically in samples from 43 patients with HNSCC. Microvessel density (MVD) was determined by immunostaining of endothelial cells with anti‐CD31 monoclonal antibody. Inducible nitric oxide synthase (iNOS) activity and cyclic guanosine monophosphatate (cGMP) levels were assessed in fresh tumor samples, whereas exons 5–9 of the p53 gene were analyzed by reverse transcriptase‐polymerase chain reaction, single‐strand conformation polymorphism analysis and were sequenced.RESULTSMMP‐1 overexpression (>10% of tumor cells) was identified in 32 tumors (74.5%), whereas elevated levels of MMP‐2 and MMP‐9 were detected in 17 tumors (39.5%) each. Tumors with MMP‐9 overexpression were characterized by significantly higher MVD (P = 0.05) and significantly higher iNOS activity and cGMP levels (P = 0.005 and P = 0.02, respectively). Moreover, p53 mutation was associated strongly with MMP‐9 overexpression (P = 0.004). Conversely, no correlation was found between MMP‐1 and MMP‐2 expression, angiogenesis, iNOS activity, cGMP levels, and p53 mutation in this series.CONCLUSIONSThis study documents the existence of a correlation between MMP‐9 expression, activity of the iNOS pathway, p53 status, and angiogenesis in patients with HNSCC. This raises the possibility that p53 mutation, which frequently is present in HNSCC, may result in increased angiogenesis and invasiveness related to increased nitric oxide and MMP production by tumor cells, ultimately contributing to tumor progression. Cancer 2002;95:1902–10. © 2002 American Cancer Society.DOI 10.1002/cncr.10916
Comparative analysis of CA125, tissue polypeptide specific antigen, and soluble interleukin‐2 receptor α levels in sera, cyst, and ascitic fluids from patients with ovarian carcinoma
Authors: Sedlaczek Paweł , Frydecka Irena , Gabryś Marian , van Dalen Arie , Einarsson Roland , Harłozińska Antonina 
Published: October 2002

AbstractBACKGROUNDThe serum markers CA125, tissue polypeptide specific antigen (TPS), and soluble interleukin‐2 receptor alpha (sIL‐2Rα) concentrations were determined in sera, cyst, and ascitic fluids from patients with malignant and benign ovarian neoplasms.METHODSCA125, TPS, and sIL‐2Rα concentrations were measured in sera, cyst, and ascitic fluids by immunoassays in 67 patients with carcinoma and in 32 patients with benign ovarian neoplasms.RESULTSCA125, TPS, and sIL‐2Rα levels were elevated significantly in sera from patients who had ovarian carcinoma compared with patients who had benign neoplasms (P < 0.001). Patients who had International Federation of Gynecology and Obstetrics (FIGO) Stage III–IV disease had significantly higher serum levels for the markers studied compared with patients who had FIGO Stage I–II disease (P < 0.001 for CA125; P = 0.02 for TPS and sIL‐2Rα). Concurrent measurement of CA125 and sIL‐2Rα in sera identified 100% of ovarian carcinomas in FIGO Stage I–II. All patients with carcinoma demonstrated markedly higher levels of CA125 and TPS for both cyst and ascites compared with corresponding sera (P < 0.001). The level of sIL‐2Rα was higher statistically in ascitic fluid compared with the level in serum (P < 0.001); however, its values in sera and cyst fluids were comparable. In ascitic fluid, the CA125 level was significantly higher in patients who had FIGO Stage III–IV disease compared with patients who had FIGO Stage I–II disease (P = 0.002), whereas such correlations were not found for TPS or sIL‐2Rα. In cyst fluids, the levels of all studied markers were independent of the FIGO stage. In cyst fluids from patients with benign ovarian neoplasms, TPS and sIL‐2Rα levels were significantly lower compared with the levels in patients with ovarian carcinoma (P < 0.001), whereas the values of CA125 were overlapping. CA125 and TPS concentrations were higher in cyst fluids compared with corresponding sera, whereas sIL‐2Rα levels were comparable and low in cyst fluids and in the circulation of patients with benign neoplasms.CONCLUSIONSIn patients with ovarian carcinoma, TPS and CA125 concentrations were significantly higher in the place of their generation compared with the concentrations in blood circulation. sIL‐2Rα values were higher in ascites compared with the values in corresponding sera, and its concentrations in sera and cyst fluids were comparable. The assessment of serum sIL‐2Rα levels showed potential complementary value to CA125 for the detection of ovarian carcinoma in early FIGO stages; however, a 9% false positive rate limited the significance of cumulative value for a combination of these circulating markers. Cancer 2002;95:1886–93. © 2002 American Cancer Society.DOI 10.1002/cncr.10917
Irinotecan plus cisplatin has substantial antitumor effect as salvage chemotherapy against germ cell tumors
Authors: Miki Tsuneharu , Mizutani Yoichi , Nonomura Norio , Nomoto Takeshi , Nakao Masahiro , Saiki Shigeru , Kotake Toshihiko , Okuyama Akihiko 
Published: October 2002

AbstractBACKGROUNDOnly 20–30% of patients with refractory or recurrent germ cell tumors (GCT) are cured by salvage chemotherapy. Irinotecan, a new derivative of camptothecin, is a potent anticancer agent against a variety of solid cancers. The current pilot study investigated the efficacy of salvage chemotherapy with irinotecan in combination with cisplatin (CDDP) or nedaplatin (NDP), a derivative of cisplatin, for GCT.METHODSThe combination chemotherapy consisted of 100–150 mg/m2 irinotecan on Days 1 and 15 or 200–300 mg/m2 on Day 1 in combination with 20 mg/m2 CDDP on Days 1–5 or 100 mg/m2 NDP on Day 1 every 4 weeks. Patients with refractory GCT, ranging in age from 17 to 43 years, received 2–11 cycles of the combination chemotherapy. The median duration of follow‐up is 28 months (8–140 months).RESULTSTwenty patients entered this study, 18 of whom were assessed for response and toxicity. The response rate was 50 % (two complete responses and seven partial responses). Nine patients remain alive without disease. However, six patients died of the disease and one patient died of a brain glioma. The 5‐year survival rate was approximately 53%. Myelosuppression was the major toxicity, but was manageable.CONCLUSIONSThis pilot study demonstrates that the chemotherapy with irinotecan in combination with CDDP or NDP showed significant anticancer activity for patients with refractory GCT, without serious side effects. Although this study comprised only a few patients, these findings suggest that the combination chemotherapy may be one of the options of salvage chemotherapy for patients with refractory GCT. Cancer 2002;95:1879–85. © 2002 American Cancer Society.DOI 10.1002/cncr.10918
Analysis of survival after laparoscopy in women with endometrial carcinoma
Authors: Eltabbakh Gamal H. 
Published: October 2002

AbstractBACKGROUNDThe effect of the laparoscopic surgical approach on the survival of women with endometrial carcinoma remains unclear. The objectives of the current study were to assess the effect of laparoscopic surgery on the survival of women with early‐stage endometrial carcinoma and to analyze the factors that affect such survival.METHODSA retrospective review of women presenting with clinical stage I endometrial carcinoma (according to the 1988 International Federation of Gynecology and Obstetrics Staging System) was performed. Women treated with laparoscopy were compared with those treated with laparotomy with regard to their characteristics, surgical procedure, treatment, surgical stage, histology, tumor grade, and recurrence‐free and overall survival. Factors affecting survival (surgical approach, histology, grade, and surgical stage) were evaluated using multivariate analysis and survival curves were constructed using Kaplan–Meier analyses.RESULTSOne hundred women underwent laparoscopy and 86 underwent laparotomy. Both groups were similar with regard to age, parity, menopausal status, lymphadenectomy, surgical stage, tumor grade, histology, and postoperative radiation therapy. Women who underwent laparoscopy and those who underwent laparotomy had similar 2‐year and 5‐year estimated recurrence‐free survival rates (93% vs. 94% and 90% vs. 92%, respectively), as well as similar 2‐year and 5‐year overall survival rates (98% vs. 96% and 92% vs. 92%, respectively). There was no apparent difference with regard to the sites of recurrence between both groups. In univariate and multivariate analyses, surgical stage, tumor grade, and histology (but not the surgical approach) were found to have a significant effect on survival.CONCLUSIONSAlthough longer follow‐up is needed, the survival of women with early‐stage endometrial carcinoma does not appear to be worsened by laparoscopy. Surgical stage, tumor histology, and tumor grade were found to significantly affect survival regardless of the surgical approach used. Cancer 2002;95:1894–901. © 2002 American Cancer Society.DOI 10.1002/cncr.10928
Self‐image in anorexia nervosa 7.5 years after initial presentation to a specialized eating disorders service
Authors: Button Eric J. , Warren Rachel L. 
Published: November 2002

AbstractObjective:The present study examined self‐image in a group of sufferers of anorexia nervosa some years after initial presentation.Method:A cohort of anorectic patients was followed up 7.5 years after presentation at a specialist locally based eating disorders service for adults. All subjects were invited to take part in a semi‐structured interview, which included completion of a repertory grid (SELFGRID) and a series of questionnaires.Results:The group as a whole showed continuing low self‐esteem. Measures of low self‐esteem were strongly related to measures of overall well‐being and particularly highly correlated with the ‘ineffectiveness’ scale of the Eating Disorders Inventory.Discussion:It is argued that the results highlight the chronic nature of low self‐esteem in anorexia nervosa and that greater emphasis should be placed on therapeutic initiatives to tackle this problem. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.