bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoclonal Antibody Targeting of Ovarian Carcinoma
Authors: Kosmas Christos , Kalofonos Haralambos P. , Hird Victoria , Epenetos Agamemnon A.
Published: April 2003

The ability to effectively define disease status in ovarian cancer after initial therapy or to selectively screen high-risk populations remains a major challenge for in vivo monoclonal antibody (mAb)-targeted approaches. Antitumour murine mAbs (HMFG1, HMFG2, H317, and H17E2) and the reshaped human antibody Hu2PLAP (against placental alkaline phosphatase; PLAP), labelled with indium-111 and iodine-123, were evaluated for their ability to localise ovarian tumours in sequential studies of our group. Thirty patients with ovarian cancer, aged 40–78 years (median 60 years) were studied with HMFG1/G2: 11, and H317/H17E2: 19 murine mAbs. Six patients with ovarian cancer aged between 36 and 65 years (median 49 years) were studied with the reshaped human Hu2PLAP mAb (5 patients) or the murine H17E2 mAb (2 patients) labelled with 111In via a new macrocyclic chelating agent (DOTA). One of these was imaged twice, with H17E2- and Hu2PLAP-DOTA-111In, respectively. In 20 out of 22 patients with radiologically measurable ovarian cancer, the presence of tumour was confirmed by the murine mAb scan and correlated well with the findings of conventional radiology diagnostic methods. One of these patients with a negative H17E2 scan and a large abdominal mass at laparotomy was found to have a PLAP-negative tumour on immunohistochemistry. Additionally, the antibody scan revealed the presence of active disease, confirmed at laparotomy/laparoscopy, in 6 out of 8 patients considered to be in clinical complete remission. Best images were obtained at 24 and 48 h after the 123I and 111In mAbs, respectively. Successful imaging with the reshaped human antibody, Hu2PLAP, was seen in 2 patients with PLAP-positive tumours. Antibodies to DOTA developed in 2 patients. In conclusion, immunolocalisation of ovarian tumours is feasible with both murine and reshaped human mAbs. The sensitivity and specificity of the method appear very high in this pilot study, and in view of the absence of toxicity, the diagnostic contribution of this approach should be evaluated prospectively. Given the low number of patients without surgically detectable disease in the present study, future investigations should include more patients with no evidence of disease in order to provide more meaningful estimates of specificity.
The Possible Prognostic Significance of p53 Immunostaining Status of the Primary Tumor in Patients Developing Local Recurrence after Breast-Conserving Surgery
Authors: Noguchi Shinzaburo , Koyama Hiroki , Kasugai Tsutomu , Tsuji Naoko , Tsuda Hitoshi , Akiyama Futoshi , Motomura Kazuyoshi , Inaji Hideo
Published: April 2003

Prognostic factors for distant metastases in patients with local recurrence after breast-conserving treatment (BCT) were studied. Fifty-six patients who developed local recurrence after BCT were recruited from 18 key hospitals/institutes in Japan. All 10 patients whose primary tumors were DCIS fared well without evidence of distant failure for a median follow-up period of 57 months (range 41–72) after the local recurrence. Inflammatory local recurrence was observed in 5 patients whose prognosis was grave: 3 with concomitant distant metastases and 1 developing them 7 months later. In the remaining 41 patients with noninflammatory local recurrence, various clinicopathological factors including age, disease-free interval, histology of the primary and recurrent tumors, axillary lymph node status, estrogen and progesterone receptor, immunohistochemical staining of erbB2 and p53 protein were evaluated as prognostic factors. Only the p53 immunostaining status of the primary tumor was found to be a significant prognostic indicator for distant metastases; distant disease-free survival at 5 years after the local recurrence was 92% for patients with p53-negative cancers and 51% for those with p53-positive cancers (p < 0.05).
Association between Tumor Angiogenesis and Borrmann Type 4 Carcinomas of the Stomach
Authors: Tanigawa Nobuhiko , Amaya Hirokazu , Matsumura Mitsuyoshi , Lu Caide , Iki Masayuki
Published: April 2003

A total of 202 gastric carcinomas, including 33 type 4 carcinomas, were studied. Intratumoral vessels were stained with an anti-CD34 monoclonal antibody before being quantitated by light microscopy (×200). The mean vessel counts for type 4 carcinomas were significantly higher than those for any other type of carcinoma, with the exception of type 1 carcinomas. Multivariate logistic regression showed that the vessel count was one of independent variables associated with type 4 carcinomas. In addition, survival analysis demonstrated that patients with type 4 carcinoma had significantly less favorable survival rates than those with other types of carcinomas.
Characteristics of Non-Hodgkin’s Lymphoma Complicated by Renal Cell Malignancies
Authors: Ohsawa Masahiko , Hashimoto Michiko , Yasunaga Yutaka , Shingu Norihisa , Aozasa Katsuyuki
Published: April 2003

Previous epidemiological studies showed an increased risk for the development of renal cell carcinoma (RCC) after adjuvant therapy or simultaneous discovery of non-Hodgkin’s lymphoma (NHL). However, clinicopathological features of NHL complicated by RCC are not well known. We summarized the clinicopathological features of 42 cases with malignant lymphoma complicated by renal tumors collected in a nationwide study in Japan. There were 27 males and 15 females, and the age at initial diagnosis of NHL ranged from 51 to 85 years (median 69 years). The clinical stages of NHL were stage I in 13 patients, stage II in 8, stage III in 8 and stage IV in 13 patients. RCC was simultaneously detected in 4 patients, within 1 year after the diagnosis of NHL in 20 and after more than 1 year in 13 patients. In the remaining 3 patients, NHL was diagnosed 1 year (2 cases) or 6 years (1 case) after nephrectomy. Histologically, all but 2 cases of NHL were diagnosed as diffuse lymphoma, with the large-cell type being the most common. The remaining 2 cases were follicular lymphoma. NHL in 35 cases (85%) were immunophenotyped as B cell type and 4 (10%) as T cell type. Renal tumors in all but 2 cases were classified as RCC: clear-cell type in 29, chromophobic type in 3, chromophilic type in 7 and Bellini duct carcinoma in 1 case. All RCC showed a cellular malignancy of grade II or III. When compared to sporadic autopsy cases of NHL in Japan, the frequency of extranodal lymphoma and B cell type was higher in the current cases (p = 0.06). In addition, leiomyosarcoma occasionally occurred among complicated renal tumors.
Hormonal Treatment of Breast Cancer: New Developments
Authors: Thürlimann B.
Published: April 2003

Hormonal treatment of breast cancer has been revisited during the last few years. New drugs have been introduced and shown to improve patient outcome, both with regard to efficacy and side effects. Historical aspects and newer developments are presented. New drugs such as second- and third-generation aromatase inhibitors and new antiestrogens have recently been introduced in the clinic or are in late development. Promising results have been obtained with new endocrine agents in third- and fourth-line treatment. Future research directions are given and the endocrine treatment of breast cancer is placed in perspective of future therapeutic options using ‘biological treatment’ to influence the regulation of cell growth and cell proliferation.
Dose-Dense Adjuvant Chemotherapy with Epirubicin Monotherapy in Patients with Operable Breast Cancer and ≥10 Positive Axillary Lymph Nodes
Authors: Fountzilas George , Nicolaides Costas , Aravantinos Gerasimos , Skarlos Dimosthenis , Kosmidis Paris , Papakostas Pavlos , Stathopoulos George P. , Kontostolis Emmanouil , Bafaloukos Dimitrios , Pavlidis Nicholas
Published: April 2003

Forty-one patients with operable breast cancer and ≥10 positive axillary lymph nodes were treated with 6 cycles of dose-dense adjuvant chemotherapy consisting of epirubicin (100 mg/m2) every 2 weeks with G-CSF support. A total of 240 cycles were administered, all of them at full dose and 19 (8%) with a delay. Thirty-eight (93%) patients completed the treatment according to the protocol. The relative dose intensity of epirubicin was 0.99. Grade 3 toxicities included anemia (3%), nausea and vomiting (5%) and alopecia (71%). After a median follow-up of 40 months, 16 (39%) patients were free of relapse. In conclusion, the present study has shown that the administration of dose-dense chemotherapy with epirubicin is feasible in the adjuvant setting with minimal toxicity.
A Randomized Comparative Study of Antiemetic Prophylaxis with Ondansentron in a Single 32-mg Loading Dose versus 8 mg Every 6 h in Patients Undergoing Cisplatin-Based Chemotherapy
Authors: Tsavaris N. , Fountzilas G. , Mylonakis N. , Athanassiadis A. , Kosmas Ch. , Karakousis C. , Bacoyiannis Ch. , Kosmidis P.
Published: April 2003

In several studies a single dose of 32 mg was compared to an ondansentron (OND) administration schedule of every 6 h, yielding no differences in overall efficacy. The aim of this randomized comparative study was to identify differences of these two schedules on an hour-to-hour control of nausea and vomiting, during the first 24 h in patients receiving cisplatin (CDDP)-based chemotherapy. One hundred ten patients were randomly assigned to two groups (A and B); all received combination chemotherapy with CDDP at a dose of 100 mg/m2. OND was administered as follows: group A: 8 mg, 30 min before the infusion of CDDP, and repeated every 6 h after the first dose (totally 4 doses) in the first 24 h, and group B: 32 mg before CDDP, as a loading dose and this was the total dose for the first 24 h. No overall difference was noticed during the first 24 h, as well as the next 3 days from the infusion of CDDP in the intensity of vomits, vomits without gastric content (retches), and nausea. In a more detailed monitoring of the distribution of emetic episodes during the first 24 h, there were important differences between these two antiemetic schedules: for group A an increased vomiting with or without gastric content between midnight and 6 p.m. was observed, and for group B between 6 p.m. and midnight (vomits with p 0.03, and without gastric content p 0.02). Preloading with the total 24-hour dose of OND 32 mg exhibits a more potent antiemetic activity during the initial 18 h, becoming weaker over the last 5 h of the first day, whereas the every-6-hour schedule leaves periods of poor emesis control between dosing intervals.
Role of Dose Intensity in Conservative Treatment ofAnal Canal Carcinoma
Authors: Ceresoli Giovanni L. , Ferreri Andrés J.M. , Cordio Stefano , Villa Eugenio
Published: April 2003

Chemoradiotherapy (CRT) is considered the standard treatment for anal canal cancer. However, the optimum schedule of therapy has yet to be defined. This study was carried out to evaluate the role of dose intensity (DI) of chemotherapy (ChT) and radiotherapy (RT) on the outcome of patients submitted to CRT. Thirty-five consecutive patients with anal canal carcinoma received a combination of RT (median dose 56 Gy) and ChT (two or more cycles of 5-fluorouracil and mitomycin C). With a median follow-up of 33 months, 83% of patients are alive without evidence of disease and 70% are colostomy-free. Five-year actuarial disease-free survival (DFS) is 74%. Univariate and multivariate analysis was performed to determine the correlation of DFS with various clinical and therapeutic parameters. Our series confirmed the prognostic negative value of a tumor size >4 cm. An average relative dose-intensity (ARDI) >0.8 was related to a better outcome both in univariate and in multivariate analysis; an overall treatment time >70 days was related to a worse DFS in univariate analysis, but these data were not confirmed by the Cox model. RT dose was not associated with DFS. In conclusion, the results of this study seem to suggest an independent prognostic role of ChT DI, as measured by ARDI. The results regarding RT DI are inconclusive, and remain a matter for further trials.
Predictive Value of Bcl-2 and Bax Protein Expression for Chemotherapeutic Effect in Gastric Cancer
Authors: Nakata Bunzo , Muguruma Kazuya , Hirakawa Kosei , Chung Y.-S. , Yamashita Yoshito , Inoue Tohru , Matsuoka Tasuku , Onoda Naoyoshi , Kato Yasuyuki , Sowa Michio
Published: April 2003

We investigated tissue staining for Bcl-2 and Bax proteins, which regulate apoptosis, as indicators of chemotherapeutic effect in patients with gastric cancer. In 23 patients with gastric carcinoma biopsy specimens were obtained endoscopically prior to chemotherapy and stained immunohistochemically with anti-Bcl-2 and anti-Bax antibodies. Patients then were treated with continuous infusion of 5-FU and cisplatin. No correlation was seen between chemotherapeutic effect and Bcl-2 or Bax alone. However, among the Bax-positive cases, the patients with Bcl-2-positive tumors were significantly more chemoresistant (p = 0.036) and had worse prognoses (p = 0.008) than Bcl-2-negative cases. Therefore, immunohistochemical staining for Bcl-2 protein may predict chemotherapeutic efficacy or guide specific therapeutic choices in treating Bax-positive tumors.
Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival
Authors: Osako Toshikatsu , Miyahara Masaki , Uchino Shinya , Inomata Masafumi , Kitano Seigo , Kobayashi Michio
Published: April 2003

We related events in immunohistochemical studies on formalin-fixed, paraffin-embedded preparations of 146 colorectal cancer patients. One hundred (68.5%) revealed cytoplasmic staining and only 3 of the 100 showed membranous staining. Western blot analysis revealed proteins with molecular masses of 185 and 155 kD following immunohistochemical membranous and cytoplasmic staining, but only a 155-kD protein following cytoplasmic staining. Amplification of the c-erbB-2 gene was detected in 2 of 44 cases (4.5%). Cytoplasmic c-erbB-2 overexpression correlated with tumor size (p < 0.01), subserosal invasion (p < 0.05), liver metastasis (p < 0.01) and Dukes’ classification. Overall survival rates and survival rates for Dukes’B patients were significantly lower in the group with cytoplasmic c-erbB-2 overexpression than in the group without cytoplasmic c-erbB-2 overexpression. Multivariate regression analysis showed cytoplasmic c-erbB-2 overexpression to be an independent prognostic factor for colorectal cancer. These results suggest that overexpression of cytoplasmic c-erbB-2 protein plays an important role in the progression of colorectal cancer and is considered to be an independent prognostic indicator of this lesion.
Vinorelbine and Carboplatin in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Authors: Kornek V. , Scheithauer W. , Glaser C. , Toth J. , Duman M. , Formanek M. , Hejna M. , Kornfehl J.
Published: April 2003

A phase II trial was performed to assess the safety and efficacy of the semisynthetic vinca alkaloid vinorelbine (VNR) when combined with carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Treatment consisted of VNR 30 mg/m2 in 250 ml saline, infused over 30 min on days 1 + 8, and carboplatin 300 mg/m2 in 1,000 ml saline, infused over 2 h on day 1. Treatment was continued in patients achieving objective response or stable disease for a total of 6 courses. 24 patients entered this trial, 12 of whom had received prior induction chemotherapy and radiation, 2 had palliative chemotherapy and 10 had only radiation and/or surgery. We observed 2 partial response (9.5%), stable disease in 6 patients (28.5%) and progressive disease in 13 (62%). The dose-limiting toxicity was myelosuppression with grade 3 or 4 leukocytopenia in 11 patients (46%). Thrombocytopenia was seen in only 2 patients. The most frequent nonhematological toxicity was an acute pain at the tumor site. None of the patients experienced neurological symptoms or chemically induced phlebitis. VNR combined with carboplatin does not appear to improve the therapeutic armentarium in recurrent squamous cell carcinoma of the head and neck.
Elevation of the Pacing Threshold: A Side Effect in a Patient with Pacemaker Undergoing Therapy with Doxorubicin and Vincristine
Authors: Wilke Andreas , Hesse Hartmut , Görg Christian , Maisch Bernhard
Published: April 2003

A 56-year-old female patient with an IgG plasmocytoma first diagnosed 5 years before underwent 3 cycles of chemotherapy according to the VAD scheme. A VVI pacemaker had been implanted 3 years earlier. After each cycle, the output of the pacemaker had to be increased as the pacing threshold had increased, resulting in a slow pulse. This case demonstrates that patients with a pacemaker that undergo chemotherapy with cardiotoxic agents must be followed carefully.
Rivizor – A New Third-Generation Aromatase Inhibitor for the Treatment of Advanced Breast Cancer after Tamoxifen Failure
Authors: Goss Paul E. , Walde David , De Coster Roland , Langenaeken Christine , Bruynseels Jan
Published: April 2003

RivizorTM (vorozole) is a new, highly potent and selective third-generation aromatase inhibitor for treatment of advanced breast cancer. In an open-label study, 30 postmenopausal women failing tamoxifen therapy received Rivizor 2.5 mg once daily until disease progression. Rivizor produced clinical benefit (partial response or no change) in 16 of 27 evaluable patients (59.3%). Five patients (18.5%) had a partial response (UICC criteria) which lasted for a median of 15 months (range 14–42.5 months), 11 patients had disease stabilization for a median of 14 months (7–24 months), and 11 patients had disease progression. Median time to first response was 3.9 months (3–27.5 months): estimated median survival time for all patients was 22.8 months (2–52.8 months) and estimated median time to disease progression was 10.8 months (1.4–42.4 months). Estradiol levels decreased to below limits of detection from 1st month of treatment until study end. Androstenedione, 17α-hydroxyprogesterone, dehydroepiandrosterone, and free-testosterone levels were unaffected by Rivizor. ACTH stimulation tests demonstrated that Rivizor does not interfere with adrenal mineralocorticoid and glucocorticoid steroid synthesis. Adverse events were mild-to-moderate. Rivizor might be an effective and well-tolerated alternative treatment for postmenopausal advanced breast cancer patients following tamoxifen failure.
N-Acetyl-β-Hexosaminidase Activity and Isoenzymes in Human Gastric Adenocarcinoma
Authors: Gil-Martín E. , Rodríguez-Berrocal F.J. , Páez de la Cadena M. , Fernández-Briera A.
Published: April 2003

The enhancement of lysosomal β-hexosaminidase degradative activity in different human cancer tissues is fairly well documented. Gastric tumors have attracted considerable attention on the basis of their social incidence and clinical recurrence. Here we report a comparative study of β-hexosaminidase activity and of its isoenzymes β-hexosaminidase A (HA) and β-hexosaminidase B (HB) from gastric adenocarcinoma and normal mucosa. Tumor β-hexosaminidase activity from crude extracts and chromatographically resolved HA and HB forms were analyzed as regards their physicochemical and enzymatic properties and were compared to similar samples obtained from control tissue. The existence of one active site in the β-hexosaminidase enzyme responsible for both N-acetyl-β-D-glucosaminidase and N-acetyl-β-D- galactosaminidase activities was determined. Apart from their relative contributions to β-hexosaminidase activities, two major differences appeared in tumor HA and HB forms with respect to the corresponding controls: (1) the presence of an atypical heat-stable HB isoenzyme in gastric adenocarcinoma, and (2) a significantly increased Vmax of the HA form acting on both p-nitrophenyl-N-acetyl-β-D-glucosaminide and p-nitrophenyl-N-acetyl-β-D-galactosaminide substrates. The results show that the β-hexosaminidase HA and HB isoenzymes from gastric adenocarcinoma display different patterns of response from the same forms from other human tumors.
Serum Level of a Soluble Receptor for Interleukin-2 as a Prognostic Factor in Patients with Gastric Cancer
Authors: Saito Hiroaki , Tsujitani Shunichi , Ikeguchi Masahide , Maeta Michio , Kaibara Nobuaki
Published: April 2003

Increased levels of a soluble receptor for interleukin-2 (sIL-2R) have been found in the serum from patients with a variety of malignancies. Levels of sIL-2R have not previously been examined in a large group of patients with gastric cancer as a possible indicator of prognosis. Serum levels of sIL-2R were measured preoperatively by an enzyme-linked immunosorbent assay in 121 patients with gastric cancer. The preoperative levels of sIL-2R in patients with gastric cancer were significantly higher than those in normal controls. An elevated level of sIL-2R was significantly correlated with certain clinicopathologic features, which included depth of invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion and clinical stage. The postoperative survival time of patients with elevated levels of sIL-2R was significantly shorter than that of patients with normal levels. Furthermore, a multivariate analysis using Cox’s proportional hazards model showed that the combination of levels of carcinoembryonic antigen and sIL-2R was an independent indicator of prognosis. Thus, the serum level of sIL-2R might be a useful prognostic indicator in patients with gastric cancer.
Bcl-2 Expression in Non-Small Cell Lung Cancers: Higher Frequency of Expression in Squamous Cell Carcinomas with Earlier pT Status
Authors: Dosaka-Akita Hirotoshi , Katabami Motoo , Hommura Humihiro , Fujioka Yasunori , Katoh Hiroyuki , Kawakami Yoshikazu
Published: April 2003

Abnormal expression of the bcl-2 gene product (Bcl-2) has been found in a wide variety of tumors, including lung cancer. In the present study, a total of 116 tumor specimens from surgically resected non-small cell lung cancer (NSCLC) patients, that were previously studied for p53 protein expression, were analyzed with immunohistochemistry for Bcl-2 expression. Forty (34%) of 116 tumor specimens showed Bcl-2 expression, which was found to occur more frequently in males than females (p = 0.049) and to be associated with smoking (p = 0.047). Bcl-2 expression was more frequently observed in squamous cell carcinomas (27 of 51, 53%) than in adenocarcinomas (12 of 55, 22%; p = 0.002), and in pT1 tumors (11 of 13, 85%) than in pT2 and pT3 tumors (16 of 38, 42%) in squamous cell carcinomas (p = 0.01). Bcl-2 expression did not correlate either with p53 protein status. We compared Bcl-2 expression in primary tumors and metastatic tumors of regional lymph nodes. Of 11 cases with Bcl-2-negative primary tumors, 10 were Bcl-2-negative in metastatic tumors except 1 case. In contrast, of 10 cases with Bcl-2-positive primary tumors, 6 lost Bcl-2 expression in metastatic tumors, while the remaining 4 cases still showed Bcl-2 expression in metastatic tumors. In the 89 potentially curatively treated patients, those with Bcl-2-positive and Bcl-2-negative tumors did not show a significant difference in survival (5-year survival rates, 56 and 42%, respectively, p = 0.2 by the generalized Wilcoxon test). These data indicate that Bcl-2 expression is frequently observed in squamous cell carcinomas with early pT status, and that it does not predict prognosis of patients with NSCLC.
S100B Protein Detection in Serum Is a Significant Prognostic Factor in Metastatic Melanoma
Authors: Hauschild Axel , Engel Gudrun , Brenner Winfried , Gläser Regine , Mönig Heiner , Henze Eberhard , Christophers Enno
Published: April 2003

The serum detection of S100B, a new melanoma marker, has shown clinical significance in early studies. The aim of our study of 1,339 serum samples from 412 different melanoma patients and 107 control patients was to prove the prognostic value of serum S100B levels in melanoma patients at different stages of disease and at follow-up (median: 30 months). Using a cutoff level of 0.2 μg/l S100B, 5 of 286 patients (1.7%) with primary tumors (stage I/II), 14/73 (19.2%) patients with locoregional metastasis (stage III) and 57/84 (67.9%) patients with advanced disease (stage IV) were S100B positive (statistically significant differences for stage I/II vs. III, I/II vs. IV, and III vs. IV, p < 0.001). The estimated overall survival time was significantly longer (p < 0.001) for patients with S100B values below 0.2 μg/l compared to patients with elevated S100B levels (≥0.2 μg/l), which was independent of the stage of disease (I–IV). Regarding prognosis, we were furthermore able to distinguish different subgroups among stage III and IV patients using S100B serum levels (p < 0.01). Patients with different cutaneous non-melanoma diseases served as S100B-negative controls. S100B serum evaluations using the Sangtec®100 IRMA are highly specific and sensitive for the detection of metastatic melanoma. S100B has been shown to be a relevant prognostic factor for survival in a study with a large sample size of melanoma patients including close follow-up evaluations.
Anti-Tumor Effect of Angiogenesis Inhibitor TNP-470 on the Human Nasopharyngeal Carcinoma Cell Line NPC/HK1
Authors: Qian Chao-Nan , Min Hua-Qing , Lin Han-Liang , Feng Gong-Kan , Ye Yan-Li , Wang Lian-Gui , Kuang Zhu-Ji
Published: April 2003

The efficacy and targeting cells of angiogenesis inhibitor TNP-470 on human squamous cell nasopharyngeal carcinoma (NPC) were investigated. The colorimetric MTT assay was used to evaluate the IC50 values of NPC/HK1 cells and human dermal microvascular endothelial cells (HDMEC) for TNP-470. An NPC human tumor model was built by tumor-bearing nude mice using the NPC cell line of NPC/HK1. TNP-470 (30 mg/kg s.c.) was injected every other day. The results showed that the IC50 of NPC/HK1 cells for TNP-470 was 3.8 times higher than that of HDMEC. A significant difference in tumor volume between control and treatment groups was found after 7 days of treatment and increased thereafter. At the end of the treatment, tumor volume was 773.7 ± 287.1 mm3 (n = 8) in the control group versus 454.5 ± 132.8 mm3 (n = 8) in the treatment group (p = 0.013); the ratio of the mean tumor volume in treated animals to that of control animals was 0.587, resulting a 41.3% decrease in tumor growth. The necrotic area was larger in the treatment group. Physical toxicity did not result from the treatment. These studies suggest that angiogenesis inhibitor TNP-470 is effective in the treatment of squamous cell NPC without obvious toxicity.
Serum Pro-Gastrin-Releasing Peptide Is a Useful Marker for Treatment Monitoring and Survival in Small-Cell Lung Cancer
Authors: Sunaga Noriaki , Tsuchiya Satoshi , Minato Koichi , Watanabe Satoru , Fueki Naoto , Hoshino Hideki , Makimoto Takeyuki , Ishihara Shinichi , Saito Ryusei , Mori Masatomo
Published: April 2003

We investigated the usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for diagnosis, treatment monitoring and the prediction of relapse and prognosis in patients with small-cell lung cancer (SCLC). Serum samples were obtained from 127 patients with primary lung cancer (48 patients with small-cell carcinoma, 31 with adenocarcinoma, 36 with squamous cell carcinoma and 11 with large-cell carcinoma). The cutoff levels of serum Pro-GRP and neuron-specific enolase (NSE) were set at 46 pg/ml and 10 ng/ml, respectively. The specificity of Pro-GRP was significantly higher than that of NSE (Pro-GRP: 93.7%, NSE: 65.8%, p < 0.01). According to the histological type of lung cancer, the positive rates of Pro-GRP were 75% (36/48) in the small-cell carcinomas, 9.7% (3/31) in the adenocarcinomas, 5.6% (2/36) in the squamous cell carcinomas and 0% (0/10) in the large cell carcinomas. The median levels of Pro-GRP in limited disease (LD) and extensive disease (ED) patients were 199 and 295.5 pg/ml, whereas those of NSE were 14.8 and 29.3 ng/ml, respectively. The positive rates of Pro-GRP in LD and ED patients were 80.0% (16/20) and 71.4% (20/28), whereas those of NSE were 70.0% (14/20) and 89.3% (25/28), respectively. The positive rate of NSE tended to elevate with the progression of disease, whereas that of Pro-GRP was already high at an early stage. Among the 29 patients with SCLC who could be followed, the serum Pro-GRP levels of 18 responders were significantly decreased after treatment (p < 0.01), whereas those of the 11 nonresponders were not significantly different between before and after treatment (p = 0.72). In the 9 patients with SCLC who relapsed, the serum Pro-GRP levels were again elevated at the time of relapse. Seventeen patients whose ratio of the Pro-GRP level after treatment to the level before treatment was below 50% (taking the levels before treatment as 100%) survived significantly longer than did the patients whose ratio was over 50% (p < 0.01). The results of the present study suggest that serum Pro-GRP has high specificity and could be a useful marker of SCLC for treatment monitoring and prognosis.
Amplification of c-myc in Hepatocellular Carcinoma: Correlation with Clinicopathologic Features, Proliferative Activity and p53 Overexpression
Authors: Kawate Susumu , Fukusato Toshio , Ohwada Susumu , Watanuki Akira , Morishita Yasuo
Published: April 2003

Expression of the proto-oncogene c-myc has been implicated in liver regeneration and hepatocarcinogenesis. The biologic significance of c-myc gene amplification in human hepatocellular carcinoma, however, is unconfirmed. We correlated c-myc gene amplification with clinicopathologic features, proliferative activity, and p53 expression in 42 resected tumors. c-myc amplification in tumor tissue was determined using a differential polymerase chain reaction, a useful procedure for the evaluation of gene amplification in archival formalin-fixed paraffin-embedded tissues, in comparison with a dopamine D2 receptor gene. Proliferative activity was estimated by numbers of argyrophilic nucleolar organizer regions and immunohistochemical nuclear labeling rates using a monoclonal antibody against Ki-67. The c-myc gene was amplified in 14 of 42 tumors (33.3%). Amplification of c-myc was more frequent in younger patients and in larger tumors, and less differentiated tumors. No correlation was noted with α-fetoprotein level or viral hepatitis state. The amplification showed positive correlation with both proliferative activity and p53 overexpression. Disease-free survival in patients showing c-myc amplification was significantly shorter than in those without amplification. These results suggest that c-myc amplification is an indicator of malignant potential and poor prognosis in hepatocellular carcinoma. c-myc amplification and p53 alteration may be coparticipating events in the progression of these tumors.
Immunohistochemical Analysis of Midkine Expression in Human Prostate Carcinoma
Authors: Konishi Noboru , Nakamura Mitsutoshi , Nakaoka Shingo , Hiasa Yoshio , Cho Masaki , Uemura Hirotsugu , Hirao Yoshihiko , Muramatsu Takashi , Kadomatsu Kenji
Published: April 2003

Midkine (MK) is a growth/differentiation factor frequently expressed at high levels in some types of human malignancies. To investigate whether MK is a useful marker in prostate carcinogenesis, immunohistochemical analysis was performed on samples of both latent and clinical prostate cancers of various stages, as well as on specimens of normal gland and prostatic intraepithelial neoplasia (PIN). Of the 80 clinical cancers examined, 69 specimens (86.3%) were immunoreactive for MK, with metastatic lesions generally showing higher expression than the corresponding primaries; normal prostate tissues were negative or showed only weak staining. Midkine was also detected in 12 of 15 latent cancers (80%) and in 12 of 16 cases of PIN (75%). In sections of whole prostate, MK showed variable expression through tumorous sections, probably in reflection of heterogeneous cell populations. The results demonstrate the possible value of MK as a marker for early and latent disease, as well as for more advanced clinical stages of prostate cancer.
Successful Primary Radiation Therapy of Adenoid Cystic Carcinoma of the Lung
Authors: Müller Anja , Stockamp Barbara , Schnabel Thomas
Published: April 2003

Adenoid cystic carcinoma is a distinctive malignant neoplasm generally arising from minor salivary glands, that arises infrequently as a primary tumor in the lung. Surgery has been considered the primary treatment, with radiotherapy generally utilized as adjuvant or palliative treatment. We report a patient in whom primary radiotherapy was sucessfully applied to treat adenoid cystic carcinoma involving the distal trachea, carina, and both main stem bronchi. A total dose of 66 Gy was delivered in 2-Gy fractions over a 7-week period. Clinically and histologically complete remission was achieved without evidence of disease during a 27-month follow up.
Detection and Clinical Significance of Lymph Node Micrometastasis Determined by Reverse Transcription-Polymerase Chain Reaction in Patients with Esophageal Carcinoma
Authors: Kijima Fumio , Natsugoe Shoji , Takao Sonshin , Aridome Kuniaki , Baba Masamichi , Yoshifumi Matsushita , Eizuru Yoshito , Aikou Takashi
Published: April 2003

We investigated micrometastasis in lymph nodes by detecting carcinoembryonic antigen (CEA) mRNA. A total of 400 lymph nodes obtained from 21 patients with esophageal carcinoma were examined by CEA-specific reverse transcription-polymerase chain reaction (RT-PCR). Serial sections of positive lymph nodes were reexamined histologically and immunohistologically. Twenty-seven lymph nodes of 11 patients were diagnosed as being positive by conventional histologic examination. CEA-mRNA positivity was found in 18 of 21 patients. Among 373 histologically negative nodes, 79 (21.2%) were positive for CEA mRNA. Of these, micrometastasis was detected in 2 by histological reexamination and in 11 by immunohistochemical staining using cytokeratin antibody. Two of 6 RT-PCR-positive patients (33.3%) had recurrent disease. Four of 11 patients (36.4%) whose nodal involvement was discovered by routine histological examination also had recurrent cancer. CEA-specific RT-PCR detected micrometastasis in lymph nodes at a higher rate than histological or immunohistochemical analysis of serial sections. Since the incidence of CEA-mRNA positivity is high in the lymph nodes of esophageal cancer patients except for those with early cancer, these patients should be treated with adjuvant therapy.
Clinical Pathway for the Management of Resectable Gastric Cancer with Peritoneal Seeding: Best Palliation with a Ray of Hope for Cure
Authors: Sugarbaker Paul H. , Yonemura Yutaka
Published: April 2003

Peritoneal seeding from primary gastric cancer occurs in 10–20% of patients. The diagnosis of this advanced disease is usually not provided by clinical studies prior to abdominal exploration. From the data available in the literature, the surgeon is forced to make an intraoperative judgement concerning the risks and benefits of an aggressive management plan versus supportive care. A strategy has evolved that utilizes peritonectomy and extended gastrectomy to maximally cytoreduce tumor combined with perioperative intraperitoneal chemotherapy. In the current state of the art, the perioperative intraperitoneal chemotherapy is heated and manually distributed to provide uniform treatment to all peritoneal surfaces and the resection site. The pharmacologic parameters have been established and the results of phase II studies are reported. Five-year survival of patients in whom a complete cytoreduction was possible is approximately 10% with a median survival of 12 months. Gastrectomy with peritonectomy to eliminate all visible implants combined with perioperative intraperitoneal chemotherapy should be used in selected patients with primary gastric cancer and carcinomatosis.
Chromosomes 7,17 Polysomies and Overexpression of Epidermal Growth Factor Receptor and p53 Protein in Epithelial Hyperplastic Laryngeal Lesions
Authors: Gale N. , Kambič V. , Poljak M. , Cör A. , Velkavrh D. , Mlačak B.
Published: April 2003

Purpose: To visualize directly a sequence of genetic changes underlying the entire spectrum of epithelial hyperplastic laryngeal lesions (EHLL) and laryngeal cancer by the use of non-isotopic in situ hybridization (ISH) for chromosomes 7 and 17 in correlation with overexpression of p53 protein and epidermal growth factor receptor (EGFR). The specific aim was to compare the results and prognostic significance between the two types of EHLL: isolated, mainly atypical hyperplasia or risky epithelium, and EHLL associated with squamous cell carcinoma (SCC). Patients and Methods: 59 tissue specimens of EHLL obtained from 34 patients, graded according to the Ljubljana classification into simple (SH), abnormal (AbH) and atypical hyperplasia (AtH), and carcinoma in situ (CIS) were included in the study. Non-fluorescent ISH for chromosomes 7 and 17 was performed by biotinylated α-satellite DNA probes. Immunohistochemical staining for EGFR and p53 protein was analyzed on the same tissue samples. Results: Polysomy for both chromosomes increased in correlation with progressive grades of EHLL. The most important finding was the statistically significant difference in chromosome copy numbers between the isolated AtH and AtH associated with SCC. Overexpression of EGFR and p53 protein was found in 61 (36/59) and 52% (31/59) of cases, respectively. The immunoreactivity for both markers increased with the grade of lesions, but the staining pattern was not so uniform in isolated EHLL. On the other hand, the immunoreactivity was expressed more constantly in EHLL adjacent to SCC. Conclusions: Numerical changes in chromosomes 7 and 17 might be associated with an upregulation of EGFR and p53 genes, and could contribute to critical events in laryngeal carcinogenesis. For daily practice, the cytogenetic and immunohistochemical analyses could be of assistance in distinguishing between low- and high-risk groups of AtH. However, the isolated forms of atypical hyperplasia need considerable further study by evaluating genetic changes with the described methods regarding their ultimate transformation to carcinoma.
Primary Sarcomas of the Central Nervous System
Authors: Merimsky O. , Lepechoux C. , Terrier P. , Vanel D. , Delord J.P. , LeCesne A.
Published: April 2003

The medical files of 14 patients with primary brain and spine sarcomas were retrospectively reviewed. Ten patients had primary brain sarcomas and 4 primary spinal sarcomas. The tumors probably originated in the brain substance or blood vessels, in the meninges or in the inner aspect of the skull. The spinal tumors originated in the nerve roots of the cauda equina and in the spinal substance or blood vessels. The most common type was angiosarcoma. Removal of the brain tumors was performed in 95% of the patients. Radiotherapy was delivered to 6 patients with brain sarcomas and to all patients with primary spinal sarcomas. Metastatic disease to the lung or pleural effusion was evident in 2 patients who underwent total removal of their tumors followed by radiation therapy.
Prognostic Significance of Nuclear Accumulation of c-myc and mdm2 Proteins in Synovial Sarcoma of the Extremities
Authors: Shen Jing-Nan , Scotlandi Katia , Baldini Nicola , Manara Maria Cristina , Benini Stefania , Cerisano Vanessa , Picci Piero , Serra Massimo
Published: April 2003

We retrospectively analysed a group of primary tumours from 32 patients with synovial sarcomas of the extremities by using immunohistochemistry on paraffin-embedded tissue samples in order to investigate the prognostic significance of the nuclear accumulation of c-myc and mdm2 proteins. Nuclear positive immunostaining for c-myc or mdm2 proteins were revealed in 9/32 cases (28%) and in 6/30 cases (20%), respectively. Since c-myc protein appears to be a key factor for keeping cells in an active proliferative stage, we also analysed the growth compartment of each tumour by using the MIB1 monoclonal antibody, specific for Ki-67 antigen. A high MIB1 index was found in 8/31 cases (26%) but was not associated either with c-myc or mdm2 nuclear positivity. Analysis of clinical outcome was performed in a subgroup of 27 patients with a minimum follow-up of 24 months. Among the clinicopathologic parameters and the biological markers, only the nuclear accumulation of c-myc was significantly associated with a higher relapse rate (p = 0.03). Accordingly, survival analysis confirmed a trend toward a poor event-free survival rate and a worse outcome in c-myc-positive cases (p = 0.12). These data demonstrate that assessment of c-myc nuclear accumulation can be useful to identify high-risk subsets of patients with synovial sarcoma of the extremities.
Relative Expression of the RET9 and RET51 Isoforms in Human Pheochromocytomas
Authors: Le Hir Hervé , Charlet-Berguerand Nicolas , Gimenez-Roqueplo Anne-Paule , Mannelli Massimo , Plouin Pierre-François , de Franciscis Vittorio , Thermes Claude
Published: April 2003

Activating mutations of the RET oncogene cause the inheritance of multiple endocrine neoplasia type 2 (MEN2). The RET pre-mRNA is spliced into several transcripts coding for multiple isoforms, including Ret9 and Ret51. When harboring activating mutations in the cytoplasmic region, the Ret51 protein displays a higher in vitro transforming efficiency as compared to the corresponding Ret9 isoform. We investigated whether a more transforming isoform was preferentially expressed in MEN2 tumors as compared to normal tissues or sporadic pheochromocytomas. By quantitative RNases protection assays, we measured the absolute abundance of the 3′ splice variants in pheochromocytomas and in normal tissues. The proportion of RET51 transcripts was highly dispersed between tumors and normal tissues. In familial tumors the proportion of RET51 transcripts was significantly larger (48.1%) than in sporadic tumors (36.75%). This result suggests that the preferential expression of the Ret51 protein isoform, even though moderate, is a growth advantage for MEN2 tumors.
A Pilot Trial of Suramin in Metastatic Breast Cancer to Assess Antiangiogenic Activity in Individual Patients
Authors: Gradishar William J. , Soff Gerald , Liu Jiangou , Cisneros Angela , French Suzanne , Rademaker Alfred , Benson III Al B. , Bouck Noel
Published: April 2003

Suramin is a polysulfonated naphthylurea with multiple potential mechanisms of action against tumors, including the ability to bind growth factors known to promote tumor angiogenesis. Using an established fixed dosing scheme for the administration of suramin in patients, a pilot study was conducted in patients with progressive, metastatic breast cancer. The primary objective of this trial is to define the effect of suramin on the angiogenic activity in individual patients using in vitro laboratory assays. The secondary objective was to assess the antitumor effect of suramin in a population of metastatic breast cancer patients. No objective tumor responses were observed in any of the 9 patients who received treatment with suramin, however 1 patient did maintain stable disease status. The strength of angiogenic activity present in patient samples was assessed by testing patient plasma in the capillary endothelial cell migration assay. Angiogenic activity followed over time was lowest in patients with the highest suramin concentrations and highest in patients with the lowest suramin concentrations. We conclude that it is feasible to continually monitor the activity of antiangiogenic agents in individual patients without relying on clinical tumor response.
Carboplatin-Gemcitabine Treatment of Patients with Transitional Cell Carcinoma of the Bladder and Impaired Renal Function
Authors: Carles J. , Nogué M. , Domènech M. , Pérez C. , Saigí E. , Villadiego K. , Guasch I. , Ibeas R.
Published: April 2003

Introduction: Bladder cancer is a frequently occurring tumour in Spain and usually affects elderly patients with renal impairment. The development of new combination therapies for such patients is thus of vital importance. Patients and Methods: Between 1997 and 1998, 17 patients with locally advanced non-surgical or metastatic bladder tumours were treated at our centres. Treatment consisted of 1,000 mg/m2 of gemcitabine administered on days 1 and 8, and carboplatin (area under the concentration curve = 5) on day 1, every 21 days. Results: The mean age of the patients [4 females (26%) and 13 males] was 69 years (range: 54–78 years). The average Karnofsky performance status was 80% (range: 50–100%). Mean creatinine clearance was 45.4 ml/min (range: 21–55 ml/min). There were 2 complete responses, 7 partial responses (RO: 56%; range 31–81%), 6 patients had stable disease and 1 disease progression. Haematological toxicities were as follows: grade I anaemia in 2 patients, grade III in 3; grade I granulocytopenia in 2 patients, grade III–IV in 4 patients; grade III thrombocytopenia in 3 patients. Toxic death occurred in the course of one grade IV neutropenic event. Non-haematological toxicities were as follows: grade I–II vomiting in 3 patients and grade III in 1. One patient had grade III hepatic toxicity. One patient had grade III renal toxicity, and 3 patients grade II alopecia. Conclusions: The above-mentioned treatment has low toxicity, is easy to administer and offers promising results in this group of patients.
Contemporaneous Bilateral Forearm Triceps Metastases from Adenocarcinoma of the Lung
Authors: Rossi Antonio , Rosati Gerardo , Chiacchio Rosistella , Manzione Luigi
Published: April 2003

Haematogenous skeletal muscle metastases from non-small-cell lung cancer (NSCLC) are rare, and are even more uncommonly observed bilaterally. Usually, NSCLC metastasizes to the liver, adrenal glands, lung, bone, central nervous system and kidney. We report a case of a long-surviving patient with contemporaneous histologically proven bilateral muscle metastases in the right and left forearm triceps, from adenocarcinoma of the lung.
HLA-DRB Genotypes in Japanese Patients with Renal Cell Carcinoma
Authors: Kojima Yasuyuki , Takahara Shiro , Nonomura Norio , Sada Masaharu , Tsuji Takayuki , Hatori Motoaki , Fujioka Hideki , Kuroda Hideya , Miki Tsuneharu , Okuyama Akihiko
Published: April 2003

Objectives: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction. Patients and Methods: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection. Results: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively). Conclusion: RCC might be linked to these two alleles in Japanese patients.