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Biomedical subjects

S Pilotti

Publications and source records attributed to S Pilotti.

At least 181 records · Page 10Linked to original sources

Human fibroblast interferon adjuvant to CO2 laser in the treatment of recurrent juvenile laryngeal papillomatosis: experience with 7 cases.

Preliminary results of adjuvant human fibroblasts interferon (IFN beta) given after CO2 laser excision in recurrent laryngeal papillomatosis in 7 adult patients are reported. Diagnostic procedure included histologic and immunohistochemical investigations to demonstrate the presence of viral cytopathic effect and for characterization of the virus. All patients underwent CO2 laser excision under general anesthesia followed by administration of IFN beta intramuscularly at the dose of 4 x 10(6) IU/day for 10 consecutive days. In the presence of complete remission, patients were followed without further therapy; in the presence of partial remission, a new combined treatment was established. All patients had a complete remission after combined treatment, but 4 subsequently developed recurrences. Treatments were always well tolerated; even cirrhotic patients showed no side effects.

Adult↗

Surgical resection in the treatment of stages I-II of small cell lung carcinoma (SCLC).

From 1981 to 1986, 17 patients with resected small cell lung carcinoma (SCLC) staged as I or II according to the new TNM classification were recruited for a prospective study to evaluate the effectiveness of surgery and postoperative chemotherapy (plus locoregional radiotherapy only when a nonradical resection was accomplished) in the treatment of early stages of the disease. Six patients received full protocol chemotherapy (6 courses) and 8 a mean of 79.1% of the planned courses. Three patients received non adjuvant treatment. Locoregional radiotherapy for residual disease was administered in 2 cases. One patient died for myelosuppression due to chemotherapy and 10 for recurrences of cancer, all within the 20th postoperative month. Metastases accounted 80% of overall recurrences. Six patients were alive and tumor-free at 18, 22, 39, 44, 47 and 51 months from resection. Actuarial observed 3-year survival was 32%.

Aged↗

Study of multiple human papillomavirus-related lesions of the lower female genital tract by in situ hybridization.

Twenty-six women with multiple human papillomavirus (HPV)-related lesions of the lower genital tract were investigated by immunohistochemistry for the internal genus-specific capsid antigen of HPV and by DNA-DNA in situ hybridization with 35S-radiolabeled probes for sequences of HPV-6/11, HPV-16, and HPV-18. The vulva was the most frequently affected site in all of these cases; the cervix was the second most frequently affected site. The lesions displayed the features of papillomavirus infection in 14 patients, and there was also histologic evidence of early neoplasia in 12 patients. The mean age of patients with and without neoplasia was 40 and 30 years, respectively. Evidence of HPV association was found in 73% of the vulvar lesions and in 40% of the other synchronous lesions by one or both methods. Viral DNA was found in 67% of patients with neoplasia and in 71% of patients without neoplasia. Eleven of 12 HPV-positive patients with neoplasia revealed the presence of HPV-16 in their tissues by in situ hybridization. On the other hand, 50% of those without neoplasia had HPV-16 DNA, whereas the presence of HPV-6/11 was found in the other 50%. The clinical course of the disease, the distribution of HPV type, and the type of antigen in patients with and without neoplasia suggest that progression to neoplasia was associated with HPV-16. These results stress the practical value of the in situ hybridization method for the identification of those patients with HPV infection who are at risk for progression to malignancy.

Antigens, Viral↗

Loss of heterozygosity in human germinal tumors.

The frequency of losses of heterozygosity has been investigated in 14 germinal tumors of the testis. Nonrandom deletion of whole or part of chromosome 11 was observed in four cases. In addition, loss of heterozygosity of all the informative loci analyzed was detected in one ovarian teratoma, indicating its post-meiotic origin. These results suggest that different genetic mechanisms (chromosomal deletions or meiotic segregation) that unmask putative recessive mutations are involved in the onset of germinal tumors.

Biomarkers, Tumor↗

High frequency of activation of tyrosine kinase oncogenes in human papillary thyroid carcinoma.

We had previously detected a transforming oncogene, designated PTC, in 25% of 20 papillary thyroid carcinomas. In order to characterize further the transforming activity of this tumour histotype, a new panel of tumour specimens from 16 patients was analysed by using a modified calcium phosphate-DNA coprecipitation transfection protocol. Tumour DNA from 10 patients (62%) displayed a transforming activity due to activation of three different oncogenes identified in four cases as PTC, in four cases as TRK, and in two cases as N-RAS. The same structural alterations of PTC and TRK (gene rearrangements) as well as of N-RAS (point mutation) detected in the NIH3T3 transformants, were also found in the original tumour DNAs, thus indicating that their activation was not due to transfection procedures. Since both PTC, a novel rearranged form of RET, and TRK display a tyrosine protein kinase activity, it is proposed that the activation of this class of oncogenes is specifically involved in the pathogenesis of papillary thyroid cancer.

Animals↗

Fine needle aspiration cytology in superficial lymph nodes: an analysis of 266 cases.

The results of fine needle aspiration cytology of superficial lymph nodes in 275 patients are discussed. Nine cases were lost to follow-up. Of the remaining 266 aspirates, 152 were classified as cytologically malignant, 79 as benign, three as suspicious for malignancy, and 32 as unsatisfactory owing to scanty cellularity. The sensitivity of cytology for metastatic cancer was 96.5%. The results of aspiration biopsy from lymphomas were less accurate (67.5% sensitivity). There were no false positives and nine (11.3%) false negatives. Open biopsy of three suspect lymph nodes proved them to be malignant. The aspiration procedure is easy, safe and reliable. The diagnosis of benignity cannot, however, be determined without an open biopsy, particularly for lymphomas.

Adolescent↗

High-resolution 1H NMR spectroscopy in the diagnosis of breast cancer.

Surgical specimens from 22 patients with infiltrating ductal carcinoma of the breast were analyzed by high-resolution 1H NMR spectroscopy at 80 and 300 MHz. Results were compared with those obtained from 9 benign (proliferative dysplasia without atypia) breast samples. NMR spectra at 80 MHz showed well-resolved water and lipid peaks so it was possible to calculate specific T1 and T2 relaxation times. The longitudinal T1 relaxation process of the water was found to be properly represented by a monoexponential function, whereas the transverse T2 decay was well accounted for by a biexponential model. Relaxation time measurements of the water were found to be a valuable tool in breast tissue characterization, in particular (a) mean T1 values from malignant and control populations are well distinguished (P less than 0.0008); (b) mean T2 values of both fast and slow components from the two populations are statistically different (P less than 0.0001) and no overlap exists in the distributions of the second component. Three-hundred-megahertz spectra allowed a detailed analysis of the lipidic component of the sample: malignant tumors were found to present in the region 1.3-1.2 ppm a species characterized by a very slow transverse relaxation time (T2 = 200-1000 ms).

Body Water↗

Cytogenetic studies in primary and metastatic neuroendocrine Merkel cell carcinoma.

Direct preparations of five primary and metastatic neuroendocrine Merkel cell carcinomas of the skin were analyzed using a G-banding technique. A recurrent structural abnormality was a rearranged chromosome #1 with involvement of p and q arms. In two cases this rearrangement appeared as a unique structural cytogenetic change. Evidence for clonal origin and karyotypic stability of this tumor was suggested by the occurrence of the same karyotypic changes in two metachronous metastases and in primary and metastatic tumor specimens of two different patients. The bands involved in rearrangements could be of significance in the molecular process of the neoplastic transformation of Merkel tumor because genes relevant to the differentiation of neural crest-derived tissue have been mapped in those regions.

Adenocarcinoma↗

Structure and expression of oncogenes in surgical specimens of human breast carcinomas.

We have performed an analysis of ras, c-myc, c-myb, c-erbB1 and c-erbB2 oncogenes in 100 surgical samples of human breast carcinomas. No point mutations have been detected at the 12th codon of c-Ha-ras and c-Ki-ras in 40 and 65 breast cancer DNAs, respectively. One out of 65 samples showed a 50-fold amplification of c-Ha-ras that, however, was not overexpressed. Alterations in the structure of c-myc, c-myb c-erbB1 and c-erbB2 oncogenes were sporadically observed. In 20 tumour samples, the study of expression of a series of oncogenes revealed that c-Ha-ras was the predominantly transcribed gene among the ras gene family whereas c-fos appeared the most constantly and significantly expressed nuclear oncogene.

Alleles↗

Monoclonal antibodies against NIH 3T3 cells transformed by human thyroid carcinoma DNA.

First cycle transformants of NIH 3T3 cells transfected with metastatic human thyroid carcinoma DNA were used as immunogen to obtain monoclonal antibodies (MAbs) against normal and transformation-related antigens. The transformed cell line (M33) was shown to contain Alu sequences. Two MAbs were selected on the basis of their differential reactivity toward untreated NIH 3T3 cells or the transformed M33 cell line. By immunofluorescence, immunoelectronmicroscopy and biochemical analysis, the first MAb (MTr1) was demonstrated to recognize an epitope on cytoskeletal filaments of proliferating murine fibroblasts. Similar MTr1-labelled filaments were also found to accumulate into cytoplast-like structures spontaneously produced by M33 cells. The characterization by immunofluorescence of MTr2, the second MAb, indicates that it recognizes a specific human antigen associated with normal thyroid epithelial cells and differentiated thyroid tumors.

Antibodies, Monoclonal↗

Clinicopathologic correlations of cutaneous neuroendocrine Merkel cell carcinoma.

A study of 50 consecutive cases (22 men, 28 women; age range, 39 to 84 years; mean age, 65 years) of cutaneous neuroendocrine Merkel cell carcinoma (CNC), 39 of whom had a mean follow-up of 34 months, revealed that the prognostic significance of the histopathologic subtyping in trabecular, solid, and diffuse variants of CNC was not as important as the pathologic postsurgical staging in localized, regional, and extraregional disease. The overall mortality was 23.5%. None of the 19 patients with localized disease died of CNC, while 11% of the 24 patients with regional disease and all seven patients with extraregional disease at presentation died of CNC. A second primary malignancy was found to be associated with the CNC in 15% of the cases. The clinical course in patients with localized disease was favorable in spite of the high number of local recurrences. Also, the presence of regional metastases was not related to an unfavorable prognosis. In 68% of the cases the disease involved the lower limbs or girdle. In ten cases the overt exophytic presentation of primary CNC was replaced by the presence of tumor masses infiltrating the inguinal soft tissues with or without nodal involvement.

Adult↗

Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.

Antineoplastic Combined Chemotherapy Protocols↗

Simultaneous presence of herpes simplex and human papilloma virus sequences in human genital tumors.

Herpes simplex virus (HSV) and human papillomavirus (HPV) sequences were analyzed in tumors of the female lower genital tract, by probing DNA from 13 intraepithelial and 30 invasive neoplastic lesions with radiolabelled HPV-16 and HPV-18 DNA as well as cloned fragments of HSV-2 DNA. Careful removal of stromal tissue from the pathological specimens allowed authentic tumor DNA to be processed. Normal genital tissue obtained from the patients and genital condylomata were included as internal controls. The presence of HPV-16 or 18 DNA was detected in 12/13 (92.3%) intraepithelial neoplasms and in 16/30 (53.3%) invasive carcinomas. No significant difference was detected in titer or frequency of antibodies to HPV group-specific antigen in sera from patients and controls. Hybridization to BgIII N fragment of HSV-2 DNA was detected in 4/13 (30.8%) intraepithelial neoplasms and 4/30 (13.3%) invasive carcinomas but in none of the control tissues. All the 8 samples harboring HSV-2 homologous sequences were also positive for HPV, supporting the hypothesis of a synergistic association between the 2 viruses. The hybridization analyses performed to study c-myc involvement in genital oncogenesis did not reveal c-myc amplification in either invasive or pre-invasive lesions.

Antibodies, Viral↗

Chromosomal abnormalities in a primary small cell lung cancer.

A cytogenetic analysis of a fresh primary tumor specimen of small cell lung cancer showed a del(3)(p14p23) in the majority of metaphases. Additional clonal changes were found in the karyotype. No abnormalities for Ha-ras, Ki-ras, N-ras, myb, or myc were detected by Southern blot analysis of the tumor DNA.

Carcinoma, Small Cell↗

Germ cell tumors of the ovary: the experience of the National Cancer Institute of Milan. I. Dysgerminoma.

The experience of the Istituto Nazionale Tumori of Milan on dysgerminoma is presented. Between 1970 and December of 1982, 25 patients were treated with a unique protocol which considered surgery and radiotherapy with different schedules according to the extension of the disease. With this treatment protocol all 13 patients at Stage I were alive and free of disease with a median follow-up of 77 months. Of 12 patients at Stage III (10 retroperitoneal and 2 retroperitoneal and peritoneal) 4 relapsed. The 5-year relapse-free survival of Stage III patients was 61.4% and the overall survival 89.5%. Amenorrhea due to radiation dose absorbed by the contralateral shielded ovary was found in 7.7%. The excellent results in Stage I patients were balanced by the unsatisfactory results in Stage III patients. A more aggressive treatment and the knowledge of other prognostic factors seem necessary.

Adolescent↗

Difficulties of a surveillance study omitting retroperitoneal lymphadenectomy in clinical stage I nonseminomatous germ cell tumors of the testis.

Between August 1981 and December 1984, 85 consecutive patients with clinical stage I nonseminomatous germ cell tumors of the testis who were suitable for close observation entered a surveillance study after orchiectomy alone. All patients had unequivocally negative chest x-ray, bipedal lymph-angiography, and computerized tomography of the abdomen and pelvis, and normal levels of alpha-fetoprotein and human chorionic gonadotropin before entering the study. Patients were followed closely for 24 to 64 months (median 42 months) with regular chest x-rays, plain films of the abdomen for lymphangiography control, and serum determinations of alpha-fetoprotein and human chorionic gonadotropin but it was difficult to obtain computerized tomography scans of the abdomen at scheduled intervals for such a long period. Followup was closed December 31, 1986. At that date 62 patients (73 per cent) were continuously free of disease after orchiectomy alone and 23 (27 per cent) suffered relapse. The over-all occurrence rate of retroperitoneal relapses was 16.5 per cent and they usually were detected late, 4 to 36 months (median 10 months) after orchiectomy. Lung metastases were detected much earlier, 2 to 10 months (median 3 months) after orchiectomy. Alpha-fetoprotein and human chorionic gonadotropin elevations preceded the radiographic demonstration of metastases in 8 patients only (35 per cent) and in 1 they were the only sign of relapse. All but 1 patient with relapse were cured with chemotherapy and/or surgery, with an over-all survival rate free of disease of 98.8 per cent. Invasion of the epididymis, rete testis and spermatic cord, primary scrotal surgery, peritumor vascular invasion and embryonal carcinoma were associated with a higher risk for relapse but it was impossible to find clear-cut indications to select patients for adjuvant chemotherapy, retroperitoneal lymphadenectomy or no treatment. Furthermore, the followup of retroperitoneal nodes proved to be much more difficult than expected. Unilateral or modified retroperitoneal lymphadenectomy facilitates management of clinical stage I nonseminomatous germ cell tumors of the testis: only the chest and markers must be followed, the status of the retroperitoneal nodes is known immediately and antegrade ejaculation is preserved in the majority of cases.

Adult↗

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization.

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.

Carcinoma, Papillary↗

Association of human papillomavirus type 16 with neoplastic lesions of the vulva and other genital sites by in situ hybridization.

The authors examined paraffin sections from 85 genital tract tissues from 49 cases for the presence of human papillomavirus (HPV) Types 6/11, 16, and 18 by stringent in situ hybridization using 35S-labeled viral DNA probes, and for viral capsid antigen by the immunoperoxidase test. The cases, selected mostly on the basis of vulvar pathology, were distributed as follows: early neoplasia (Group I, 6 cases); early neoplasia with viral cytopathic effect (CE) (Group II, 24 cases); and papillomavirus infection (PVI) (Group III, 19 cases). Available tissues from all affected sites were examined when the disease was multicentric. One or more viral DNAs were identified in 58% of 77 tissues from Groups II and III and in 2 of 8 tissues from Group I. HPV-6/11, HPV-16 and HPV-18 DNAs were detected, respectively, in 25, 24, and 2 tissues; 3 tissues were infected simultaneously with either two or three viruses. Viral DNA was identified at more than one site in 14 of 30 DNA-positive patients; in 10 of these, a single type was detected at all sites in the same patient. The viral DNA was localized mostly in areas showing viral cytopathology. The presence of HPV-16 correlated with neoplasia. HPV-16 DNA was identified in the 2 virus-positive tissues showing neoplasia, in 17 of 20 (85%) of the DNA-positive tissues showing neoplasia with CE, and in 5 of 25 (20%) of the DNA-positive tissues showing PVI. Conversely, HPV-6/11 was found in 25% of the DNA-positive tissues showing neoplasia with CE and in 80% of the cases of PVI. An HPV genome was identified in neoplastic cells in 14 instances; in all but 1 case, the genome was HPV-16. The association of HPV-16 with neoplasia was seen for both vulvar and cervical lesions. Viral antigen was detected in 83% of lesions associated with HPV 6/11 and in 62% of lesions associated with HPV-16.

Adult↗