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Biomedical subjects

G Baiocchi

Publications and source records attributed to G Baiocchi.

At least 37 records · Page 2Linked to original sources

High-dose cisplatin and bleomycin neoadjuvant chemotherapy plus radical surgery in locally advanced cervical carcinoma: a preliminary report.

One course of chemotherapy containing cisplatin and bleomycin as a neoadjuvant treatment was given to 26 consecutive patients with previously untreated stage IB (bulky disease)-III cervical carcinoma and followed by radical surgery. After chemotherapy responses were detected in 23 patients (5 complete and 18 partial; overall, 88%) and permitted radical surgery in 21 cases (81%). Surgery consisted of type III-IV radical hysterectomy plus systematic para-aortic and pelvic lymphadenectomy. At histologic examination, complete responses were found in 5 (19%) and partial responses in 16 (62%) cases. The average number of lymph nodes removed was 61 (range, 38-118). A lower than expected incidence of lymph node metastases was detected (2/21, 9.5%). The chemotherapy-induced toxicity was mainly represented by nausea and vomiting. Chemotherapy did not seem to complicate surgery in these circumstances, even though moderate-degree postoperative complications occurred in 48% of cases. Eighteen months median follow-up time (range, 11-23) from hystological diagnosis has been reached in the operated patients, and no recurrences have been detected so far.

Adult↗

Effect of recombinant human interferon-alpha 2b on receptors for steroid hormones and epidermal growth factor in patients with endometrial cancer.

Interferons (IFNs) may modulate oestrogen (ER), progesterone (PR) and epidermal growth factor (EGFR) receptor expression in vitro. ER, PR and EGFR levels in tumour specimens taken from 13 patients with endometrial adenocarcinomas before and after 5 days' intramuscular treatment with 5 x 10(6) U per recombinant human leucocyte interferon-alpha 2b (rh IFN-alpha 2b). After treatment, ER (P less than 0.01) and PR (P less than 0.05) levels were significantly increased with a simultaneous reduction of EGFR content (P less than 0.05). Since the expression of ER and PR characterises more differentiated hormono-sensitive tumours, while EGFR are preferentially expressed in less differentiated tumours, the increase of steroid hormone receptor levels with the reduction of EGFR expression suggests that rh IFN-alpha 2b may induce endometrial cancer cell differentiation. Moreover, the decrease of EGFR levels may explain the antiproliferative effect of IFNs.

Adenocarcinoma↗

The value of squamous cell carcinoma antigen in patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.

Serum levels of squamous cell carcinoma antigen were measured in 688 samples from 119 patients with cervical cancer. Ninety-seven patients had primary tumors and 22 had recurrent disease. Serum samples were obtained before each cycle of chemotherapy, before surgery, at least 4 weeks after surgery, and at 2- to 3-month intervals during follow-up from 78 of the patients with locally advanced cervical cancer who were receiving neoadjuvant chemotherapy. Squamous cell carcinoma antigen serum levels were elevated (greater than 2.5 ng/ml) in 71% of the patients with primary tumors and in 77% of the patients with recurrent carcinomas. The percentage of positivity increased significantly with stage (p = 0.03) and was higher in squamous cell tumors than in adenocarcinomas (p less than 0.001). Pretreatment squamous cell carcinoma antigen levels were not predictive of neoadjuvant chemotherapy response; however, the serial measurement during chemotherapy showed a good correlation with clinical response. In the patients who had surgery, squamous cell carcinoma antigen positivity did not correlate to pathologic findings (lymph node status, cervical and parametrial infiltration). Disease-free survival was significantly longer in patients with squamous cell carcinoma antigen pretreatment values that were lower than 5 ng/ml, compared with patients with marker higher than 5 ng/ml (p less than 0.01). Abnormal squamous cell carcinoma antigen serum levels preceded the clinical detection of recurrence in eight of 11 patients with a median lead time of 5 months.

Adenocarcinoma↗

Cathepsin D assay in ovarian cancer: correlation with pathological features and receptors for oestrogen, progesterone and epidermal growth factor.

Using an immunoradiometric assay, Cathepsin-D (Cath-D) concentrations were measured in the cytosol of 68 normal and neoplastic human ovarian tissues. Cath-D levels were higher in malignant tumours than in normal tissue samples (P less than 0.01) and benign tumours (P less than 0.01). In six out of seven cases, metastatic deposits showed Cath-D concentrations higher than the respective primary tumours. Using 12 of 17 pmols.mg-1 protein as cut-off levels, the Cath-D status (high or low) was not related to any pathological parameter. Moreover, no correlation was found between Cath-D levels and receptors for oestrogen, progesterone and epidermal growth factor. Our results indicate that ovarian tumours produce Cath-D. Further studies are needed to evaluate whether this protein could represent a prognostic factor for this neoplasia.

Biomarkers, Tumor↗

Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer.

We investigated the feasibility of a programme of autologous blood stem cell (ABSC) harvesting and transplantation in 13 patients with advanced ovarian cancer, previously untreated by chemotherapy or radiotherapy and entering a phase II study of high-dose cisplatin, etoposide and carboplatin with haematopoietic stem cell rescue. Prior to high-dose treatment all patients underwent two courses of cisplatin and cyclophosphamide. An 8-fold increase of the peripheral colony forming unit granulocytic-macrophage (CFU-GM) was observed during recovery from myelosuppression after the first chemotherapy course. The second course determined a 2.5-fold increase of peripheral CFU-GM. In 70% of enrolled patients (nine patients) we were able to perform ABSC harvesting by leukaphereses; in the apheresed patients we harvested an average of 20.8 x 10(4)/kg CFU-GM (range 10.9-37.0). Haematopoietic trilineage engraftment, established as the number of days necessary to reach white blood cells (WBC) greater than 1.0 x 10(9)/l, polymorphonuclear leucocytes (PMN) greater than 0.5 x 10(9)/l and platelets (PLT) greater than 50 x 10(9)/l, occurred very promptly and was sustained in the same series after high-dose cisplatin, carboplatin and etoposide, followed by autologous blood stem cell transplantation (ABSCT). In our experience we found a significant correlation (r = 0.77; P less than 0.05) between CFU-GM infused dose and the engraftment speed of PMN. We conclude that the combination of cisplatin and cyclophosphamide is effective in mobilizing haematopoietic progenitors in the peripheral blood of patients with advanced ovarian cancer, previously untreated by chemoradiotherapy. Moreover, ABSCT is capable of rapidly restoring the haematopoietic function after high-dose treatment and for this reason it represents a particularly advisable therapeutic option for the treatment of solid tumours because these patients are commonly older than 50 and can be excluded from bone marrow transplantation.

Adult↗

High dose chemotherapy with cisplatin, VP16 and carboplatin with stem cell support in patients with advanced ovarian cancer.

Authors treated 4 patients suffering from advanced ovarian cancer with high-dose chemotherapy and autologous peripheral blood stem cell (APBSC) or autologous bone marrow stem cell (ABM) as hematopoietic support. In three patients were collected peripheral blood stem cells using a fully automated blood cell separator during hematopoietic recovery following aplasia induced by non-intensive chemotherapy (cisplatin 200 mg/m2 and cyclophosphamide 1,500 mg/m2). Hemopoietic reconstitution of the four patients submitted to APBSC or ABM support after high-dose chemotherapy (cisplatin 100 mg/m2, VP16 650 mg/m2 and carboplatin 1,800 mg/m2) showed the low hematological toxicity of our treatment with APBSC support. Moreover, the drug combination of cisplatin and cyclophosphamide has clinical activity in ovarian cancer and it is an optimal association to mobilize and harvest large number of PBSC.

Adult↗

Constitutive expression of leukemia inhibitory factor RNA by human bone marrow stromal cells and modulation by IL-1, TNF-alpha, and TGF-beta.

Recent in vitro studies indicate that bone marrow mesenchymal elements, residing in close proximity to hematopoietic cell populations, elaborate a network of cytokines that are, at least partially, responsible for modulating the growth and maturation of the latter compartment. Leukemia inhibitory factor (LIF), a molecule with both positive and negative regulatory activities, has been implicated in murine embryogenesis and hematopoiesis. We demonstrate that cultured normal human bone marrow stromal cells constitutively express LIF message. Further, exposure of these cells to other hematopoietic modulators including interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha) (but not interferon-alpha [IFN alpha]) increases the level of LIF RNA. Interestingly, cultured stromal cells derived from three of four patients with chronic myelogenous leukemia showed enhanced LIF expression. These observations suggest that LIF may participate, either alone or through interaction with other cytokines, in the bone marrow microenvironment-mediated influence on both normal and malignant hematopoietic processes.

Bone Marrow↗

Constitutive and induced expression of growth factors in normal and chronic phase chronic myelogenous leukemia Ph1 bone marrow stroma.

Study of growth factor RNA levels in the stromal cells derived from the adherent layer of long-term bone marrow culture demonstrated constitutive expression of transforming growth factor beta 1 (TGF-beta 1) and macrophage colony-stimulating factor. These cells did not express granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interleukin (IL) 1 alpha, IL-1 beta, IL-3, and IL-6. However, granulocyte colony-stimulating factor expression could be induced by recombinant human IL-1 beta; while IL-6 could be induced by both IL-1 beta and tumor necrosis factor-alpha. No differences could be detected between adherent layers established from normal and benign phase Ph1 chronic myelogenous leukemia bone marrow. The uninduced expression of TGF-beta 1, a potent hematopoietic cell growth inhibitor, suggests that stromal cells play an inherent role in regulating the proliferation of adjacent bone marrow hematopoietic progenitor cells. However, a defect in stromal TGF-beta 1 production cannot account for the profoundly expanded myeloid compartment in chronic phase chronic myelogenous leukemia. In contrast to the constitutive expression of TGF-beta 1 and macrophage colony-stimulating factor, hematopoietic growth factors are only expressed following a proper stimulation.

Biological Factors↗

Recombinant alpha-2b-interferon enhances the circulating levels of a 90-kilodalton (K) tumor-associated antigen in patients with gynecologic and breast malignancies.

The circulating levels of a 90-kilodalton (K) tumor-associated antigen were measured in the blood of 43 patients with gynecologic and breast malignancies who underwent a short course of recombinant alpha-2b-interferon (rIFN alpha-2b) (3 million U/m2/d intramuscularly [IM] for 3 days). Of the 43 patients, 23 showed abnormal 90-K levels (greater than 1.7 U/ml). A significant increase of antigen levels was already observed 24 hours after the first administration and persisted throughout the investigation period. Of 20 patients with 90-K levels below the normal limit, 12 went over the normal cutoff value after two rIFN alpha-2b injections. No significant modifications of 90-K levels were detected in nine women receiving rIFN alpha-2b for the treatment of genital condylomata. The serum levels of two other tumor-associated antigens, CA 125 and CA 15-3, were not modified by rIFN alpha-2b administration. The ability of rIFN alpha-2b to increase the circulating levels of 90-K might have important clinical implications for the serodetection of cancer.

Antigens, Neoplasm↗

Endometrioid stromal sarcomas arising from ovarian and extraovarian endometriosis: report of two cases and review of the literature.

Endometrioid stromal sarcomas arising from endometriosis are rare tumors. Two cases from our institution are presented and the literature is reviewed. The patients tend to be nulliparous. Presentations usually are related to the symptoms of a pelvic mass. However, extraovarian origin was frequently accompanied by hemorrhage. The tumors are usually of low histologic grade. Among 18 patients with ovarian origin, only 2 were reported dead of disease. However, 5 of 13 patients with extraovarian origin died mostly as a result of recurrent disease. Deaths generally occurred within 3 years of diagnosis. The efficacy of chemotherapy, radiotherapy, or hormonal therapy in the adjuvant or recurrent setting cannot be determined from the available reports.

Adult↗

Steroid hormone receptors in carcinoma of the cervix: lack of response to an antiestrogen.

Levels of estrogen (ER) and progesterone (PR) receptors were measured in 81 patients with primary cervical cancer. In 10 patients, receptor levels were evaluated before and after a short course of tamoxifen treatment. Fifty-six percent of cervical tumors contained ER, and 58%, PR. Receptor level and expression were not related to any clinical and histological characteristic. Moreover, both survival time and response to neoadjuvant chemotherapy did not correlate with the presence of ER and PR. Tamoxifen treatment did not influence ER and PR levels. Our results suggest that steroid hormone receptors are of little value in the management of cervical cancer, and that in this neoplasia, ER is probably not functional.

Antineoplastic Agents↗

Type II estrogen binding sites in human peripheral blood mononuclear cells: variations during the menstrual cycle.

We have previously reported that human peripheral blood mononuclear cells (PBMC) contain type II estrogen binding sites (type II EBS). In this study, the fluctuations of type II EBS during the menstrual cycle were analyzed in 6 normally menstruating women. Approximately 3 times higher levels of type II EBS were found in the periovulatory period with respect to both follicular and luteal phases. In postmenopausal women the mean type II EBS levels were similar to those observed in the follicular phase of the cycle. However, in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of type II EBS levels. Tamoxifen was also found to compete with 17 beta-estradiol for type II EBS in PBMC, although to a lesser extent than diethylstilbestrol.

Adult↗

A primary amelanotic melanoma of the vagina diagnosed by immunocytochemistry.

A case of primary malignant melanoma of the vagina is discussed. The lesion consisted of a nodule in the middle third of the vagina that was histologically suspected of being an unpigmented malignant melanoma. The melanocytic origin of the lesion was confirmed by the pattern of reactivity to a battery of human melanoma associated antigens and to class 1 and 2 histocompatibility antigens. No secondary lesions or alternative primary sites were found. The patient underwent radical hysterectomy with bilateral salpingooophorectomy, total vaginectomy and vulvectomy, radical inguinal, pelvic and paraaortic lymphadenectomy. The pathology report showed the presence of multiple neoplastic foci in the vagina. Although the removed lymph nodes were histologically free of metastases, microscopic foci of neoplastic cells were detected by immunohistochemistry in three lymph nodes. There is no evidence of recurrence at the twelfth postoperative month. Our results show that immunohistochemical techniques may usefully complement diagnostic histopathology in the diagnosis of female genital tract melanoma.

Aged↗

Predictive value of multiple tumor marker assays in second-look procedures for ovarian cancer.

Sera from 51 ovarian cancer patients in clinical remission undergoing a second-look operation were studied. CA 125, CA 15-3, and 90K assays were performed in the week preceding surgery. Twenty-seven patients (53%) had no evidence of disease; 3 (6%) and 21 (41%) had microscopic and macroscopic disease. All patients but two with no evidence of disease had normal CA 125 serum levels, as did the three cases with microscopic disease and 6 patients with macroscopically detectable tumor. Of 17 patients with high CA 125 values, 15 (88%) were found to have persistent disease. Hence, the sensitivity and specificity of a CA 125 assay were 62 and 93%, respectively. CA 15-3 levels were low in all patients with no evidence of disease, in 2 cases with microscopic disease, and in 2 cases with residual tumor greater than 1 cm. All patients with high CA 15-3 titers had a positive second-look. The sensitivity and specificity of assay were 69 and 100%, respectively. With the 90K assay, 4 false-positive and 4 false-negative results were found and the sensitivity and specificity were 69 and 67%, respectively. However, 3 of 4 cases with a false-positive 90K assay had recurrence of disease with 7, 9, and 20 months later. Combination of the three markers increased sensitivity to 79%. These data suggest that more effective surveillance of disease status at second-look is obtained by using a combination of tumor marker assays.

Antigens, Tumor-Associated, Carbohydrate↗

Circulating tumor markers in cervical cancer.

Serum levels of CA 19-9, CA 125 and CA 15-3 were measured in 91 patients with cervical cancer (16 with intraepithelial neoplasia and 75 with invasive cancer). In 35 patients with locally advanced cervical cancer, serum marker levels were measured at monthly intervals during neo-adjuvant chemotherapy. CA 19-9 was found to be abnormally high only in advanced stages with an overall sensitivity of 7.3%. CA 125 and CA 15-3 were elevated in 31.9 and 23.1% of the patients, respectively, with a combined sensitivity of about 40%. The mean values of CA 125 and CA 15-3 were positively related to clinical stage and tumor differentiation. CA 125 and CA 15-3 values were correlated with response to chemotherapy in more than 80% of the cases. These findings suggest that CA 125 and CA 15-3 could be usefully employed in the management of cervical cancer.

Adult↗

Epidermal growth factor receptor expression in gynecological malignancies.

Epidermal growth factor receptor (IEGF-R) levels were analyzed in 72 gynecological tumor specimens. Measurable EGR-R levels were found in a significant percentage of ovarian and uterine tumors. Moreover, all vulvar epidermoid carcinomas and uterine sarcomas analyzed were EGF-R positive. In all tumor types examined, scattered EGF-R levels were observed. Higher EGF-R levels were found in metastatic than in primary ovarian tumors. Moreover, EGF-R were found to be more expressed in less differentiated than in well-moderately differentiated endometrial tumors. Our results suggest a role of EGF or EGF-like substances in regulating the growth of gynecological malignancies, and indicate EGF-R expression as a possible prognostic factor.

ErbB Receptors↗

Multiple serum markers in patients with endometrial cancer.

Serum levels of carcinoembryonic antigen (CEA), CA 125 and CA 15-3 were measured in 47 patients with endometrial cancer and 20 with endometrial hyperplasia. Before treatment elevated serum levels of CEA, CA 125 and CA 15-3 were found in 14, 43 and 32% of cancer patients, respectively. In the 20 patients with endometrial hyperplasia, CEA and CA 15-3 values were normal, while elevated CA-125 titers were detected in 1 case. There was an increasing incidence of abnormal levels of all markers in relation to a higher tumor stage (stage I: 36%; II: 66%; III: 100%). The percentage of positive marker values increased in case of deep myometrial infiltration (greater than M1) and/or poorer tumor differentiation (greater than G1). However, only percent increase in CA 15-3 positivity was significantly higher in more infiltrating (greater than M1, 7 vs. 65%, p less than 0.01) and less differentiated (greater than G1, 0 vs. 47%, p = 0.01) tumors. These findings suggest that CA 15-3 is in some way associated with the prognostic factors of the disease. All patients except 2 with no evidence of disease after surgery had normal serum marker values. Moreover, CA 125 and CA 15-3 levels reflected the clinical course of the disease during chemotherapy and seemed to be useful for monitoring response to treatment.

Aged↗

Randomized clinical trial comparing systemic interferon with diathermocoagulation in primary multiple and widespread anogenital condyloma.

Two hundred three patients (median age 26 years; range 18-45) with untreated multiple and widespread anogenital condyloma were randomly assigned to one of four study arms in order to compare the efficacy, toxicity, and tolerability of recombinant interferon alpha-2b with those of diathermocoagulation. Of 200 evaluable patients, 51 were treated intramuscularly (IM) with 3 x 10(6) U (3 MU)/m2 daily for 3 weeks (total dose 63 MU/m2), 50 received subcutaneous thrice-weekly injections of 3 MU/m2 for 4 weeks (total dose 36 MU/m2), 51 underwent diathermocoagulation, and 48 were not treated and were used as a control group. Six months after the end of treatment, the overall response rate (complete and partial responses) was 70%: 57 and 82% for patients receiving interferon alpha-2b (IM and subcutaneously) and diathermocoagulation, respectively, and 8% for the control group. After 6 months from therapy, no significant differences in complete response were found among the different types of treatment: 20, 20, and 35% for the two interferon groups and the diathermocoagulation group, respectively. Fifteen and two complete responders in the cauterization and interferon groups, respectively, experienced disease recurrence (P less than .01). All patients given interferon therapy complained of flu-like symptoms, which declined progressively after the first week of treatment. Fatigue, lasting as long as patients received interferon, was the most prevalent chronic side effect. We conclude that systemic recombinant interferon alpha-2b is active in treating patients with primary condyloma lesions and does so as well as cauterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗