Principal sulcus and posterior parieto-occipital cortex lesions in the monkey.

In order to assess the roles of the posterior parieto-occipital and principal sulcus cortices in processing spatial information, both with and without delays, monkeys were given lesions of one or the other area or no lesion and tested on a series of conditional discrimination tasks. There were six basic tasks, and the cue locations differed from the response locations within each task. The first two had mixed dimensions in that the location of the cue indicated the color of the correct response alternative or the color of the cue indicated the correct response location. The animals were trained preoperatively on these tasks and then tested for postoperative retention. For the next two tasks color was the only relevant dimension, but different colors were used for the cues and response alternatives. For the final two tasks location was the only relevant dimension. When an animal learned a given task it was subsequently tested on it with a 5-sec. delay. The deficits observed suggest that the roles of these areas can not be expressed simply in terms of spatial or delay functions. No group appeared to be impaired on any delay task on which it was tested. The animals with the posterior cortex removed had a great deal of difficulty in using information from one dimension to identify the correct response alternative by the other dimension, but not when the relevant cue and response dimensions were the same. These results suggest that the posterior parieto-occipital area is involved in making associations across dimensions with in the visual modality. The animals with the principal sulcus removed appeared to have difficulty only when they were required to respond with reference to the colors of the response alternatives. On such tasks the relevant dimension (color) was not available until the presentation of the response array. On the other tasks the correct response location could be determined from the cue presentation alone, that is, before the presentation of the response array. This suggests that these animals had a tendency to respond without reference to the color dimension, but rather just to the presentation of the response array, and therefore a principal sulcus function of inhibiting a response until the appropriate information has been processed.     

Neoadjuvant cisplatin plus ifosfamide in patients with stage IIB cervical cancer: a single center phase II study

The objective of this study was to evaluate cisplatin plus ifosfamide as neoadjuvant chemotherapy with regard to toxicity and clinical response in patients with stage IIB cervical cancer. Sixty-eight patients with previously untreated stage IIB cervical cancer were given two cycles of chemotherapy: cisplatin 20 mg m⁻² on Days 1–5, infused over 1 h; ifosfamide 1.2 g m⁻² on Days 1–5 infused over 30 min. Mesna 120 mg m⁻² was administered as a bolus 15 min before ifosfamide, and a continuous infusion, delivering Mesna 1.2 g m⁻², was given subsequently over the next 16 hours. The treatment cycle was repeated on day 21. Responders were then randomized to surgery or radiation therapy. All 68 patients were evaluable for toxicity. Toxicity was found to be acceptable. One patient died at home one month after completion of the second treatment cycle. There was one grade 4 thrombocytopenia. Grade 3 toxicities included anemia in four patients, leucopenia and nausea and vomiting in one patient each. Sixty-two patients were evaluable for response. A clinical response was documented in 44 of the 55 evaluable patients (80%), with 17 complete responses (31%) and 27 partial responses (49%) (95% confidence limits 69%–91%, 19%–43%, and 36%–62% respectively). The intent-to-treat response rate was 64.7%. Twenty-one patients were randomized to surgery and 23 patients to radiation therapy. Amongst the eight patients with a complete clinical response, one patient had a complete pathological response and one patient had residual intra-epithelial neoplasia. The drug combination of cisplatin plus ifosfamide had acceptable toxicity and gave a clinical response rate of 80% in previously untreated patients with stage IIB cervical cancer.     

Effect of the viable-yellow (A(vy)) agouti allele on skin tumorigenesis and humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice

We previously reported that papillomas can arise from the follicular epithelium of v-Ha-ras transgenic TGxAC mice. Since the viable-yellow mutation (A(vy)) of the mouse agouti gene which regulates coat color pigmentation by acting within the micro-environment of the hair follicle has been shown to function as a tumor promoter in the liver, we hypothesized that it may also play a role in TGxAC skin tumorigenesis. Endogenous agouti protein product was detected in the outer root sheath of anagen hair follicles following plucking of the hair shaft, but not in the interfollicular epithelium, in TGxAC mice on an FVB/N genetic background. It was also detected in papillomas from these mice produced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment or plucking. Expression of the A(vy) allele in the v-Ha-ras transgenic TGxAC mouse line results in an approximately 2-fold increase in papilloma development compared with controls which did not carry the A(vy) allele following twice-weekly treatment with 1.25, 2.5 or 5.0 microg TPA. In addition, TPA-treated, papilloma-bearing F1 mice which carried the A(vy) allele, but not F1 mice which did not carry the A(vy) allele, exhibited a syndrome of humoral hypercalcemia mediated by parathyroid hormone-related protein (PTHrP) that led to weight loss, hypercalcemia and hypophosphatemia. Thus, we conclude that the A(vy) allele can influence the development of skin tumors and PTHrP-mediated humoral hypercalcemia in v-Ha-ras transgenic TGxAC mice.      

Determination of malondialdehyde-induced DNA damage in human tissues using an immunoslot blot assay

Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1- dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post- labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.      

A rare association of synchronous intraductal carcinoma of the breast and invasive carcinoma of ectopic breast tissue of the vulva: case report and literature review

Abstract.   Intra M, Maggioni A, Sonzogni A, De Cicco C, Machado LS, Sagona A, Talakhadze N. A rare association of synchronous intraductal carcinoma of the breast and invasive carcinoma of ectopic breast tissue of the vulva: case report and literature review. Int J Gynecol Cancer 2006; 16(Suppl. 1): 428–433.
Only 17 cases of breast carcinoma arising in vulvar ectopic mammary tissue have been reported. We present a unique case of synchronous pure intraductal carcinoma of the breast (DCIS) and invasive carcinoma of ectopic breast tissue of the vulva. A 53-year-old woman presented with a 2-cm nodule in left labium major of the vulva. A surgical biopsy revealed an invasive carcinoma of ectopic mammary tissue. The mammography showed irregular microcalcifications of the right breast. The patient underwent left hemivulvectomy, bilateral inguinal sentinel lymph node biopsy, and radioguided breast resection (radioguided occult lesion localization) of the microcalcifications. The definitive histology revealed negative inguinal sentinel nodes, no further residual tumor in the vulva, and a high-grade (grade 3) DCIS in the breast. The synchronous occurrence of primary breast carcinoma and ectopic breast tissue carcinoma in the vulva is an extremely rare finding, only once previously being reported and leading to unsolved problems of differential diagnosis. The presence of a pure DCIS of the breast makes this case really unique, definitively confirming the independent primary origin of both mammary tumors. The inguinal sentinel node biopsy avoided a bilateral inguinal dissection.     

人肝癌细胞株VEGF/VEGFR的检测及意义探讨

目的：筛选血管内皮生长因子（vascular endothelial growth factor，VEGF）高表达肝癌细胞株，为进一步研究VEGF在肝癌治疗中的作用提供理论依据。并探讨VEGF受体在肝癌细胞株的表达及意义。方法：ELISA法及Western blot法分别检测人肝癌细胞株培养上清及细胞内VEGF蛋白的表达。免疫细胞化学方法检测VEGFR在人肝癌细胞中的表达。结果：5株肝癌细胞株均见VEGF蛋白表达，其中SMMC-7721的VEGF表达量最高，VEGF特异性受体Fit-1在HepG2、HHCC、SMMC-7721、Bcl-7402见阳性表达，KDR在HepG2、HHCC、Bel-7402、QGY-7701见阳性表达。结论：肝癌细胞株中VEGF表达量不尽一致，VEGF在肝癌发生发展中可能存在自分泌作用方式。     

Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer.

PURPOSE: Selective lymphadenectomy is widely accepted in the management of endometrial cancer. Purported benefits are individualization of adjuvant therapy based on extent of disease and resection of occult metastases. Our goal was to assess effects of the extent of selective lymphadenectomy on outcomes in women with apparent stage I endometrial cancer at laparotomy. PATIENTS AND METHODS: Patients with endometrial cancer who received primary surgical treatment between 1973 and 2002 were identified through an institutional tumor registry. Inclusion criteria were clinical stage I/IIA disease and procedure including hysterectomy and selective lymphadenectomy (pelvic or pelvic + aortic). Exclusion criteria included presurgical radiation, grossly positive lymph nodes, or extrauterine metastases at laparotomy. Recurrence and survival were analyzed using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: Among 509 patients, the median number of lymph nodes removed was 15 (median pelvic, 11; median aortic, three). Pelvic and aortic node metastases were found in 24 (5%) of 509 patients and 11 (3%) of 373 patients, respectively. Patients with poorly differentiated cancers having more than 11 pelvic nodes removed had improved overall survival (hazard ratio [HR], 0.25; P < .0001) and progression-free survival (HR, 0.26; P < .0001) compared with patients having poorly differentiated cancers with 11 or fewer nodes removed. Number of nodes removed was not predictive of survival among patients with cancers of grade 1 to 2. Performance of aortic selective lymphadenectomy was not associated with survival. Three (27%) of 11 patients with microscopic aortic nodal metastasis are alive without recurrence. CONCLUSION: These data add to the literature documenting the possible therapeutic benefit of selective lymphadenectomy in management of patients with apparent early-stage endometrial cancer.     

Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.