Characterization of a new MUC1 monoclonal antibody (VU-2-G7) directed to the glycosylated PDTR sequence of MUC1.

A monoclonal antibody (MAb), VU-2-G7, was generated against a synthetic 60-mer MUC1 triple tandem repeat peptide with N-acetyl-galactosamine (GalNAc) O-linked to the threonine in the PDTR region of each repeat (3M GalNAc). VU-2-G7 and 8 MUC1 MAbs (VU-3-C6, VU-4-H5, 139H2, A76-A/C7, VU-12-E1, BCP9, MF11 and BW835) were tested against various glycosylated and nonglycosylated MUC1 tandem repeat peptides. VU-2-G7 showed strong reactivity with its immunogen, 3M GalNAc, and much lower reactivity with the nonglycosylated 60-mer MUC1 triple tandem repeat peptide. VU-2-G7 showed no reactivity with a 60-mer MUC1 triple tandem repeat peptide modified at the PDTR region or with a 60-mer MUC1 triple tandem repeat peptide with 3 GalNAc per repeat outside the PDTR region (9M GalNAc). In ELISA and flow cytometry, VU-2-G7 ubiquitously reacted with 4 MUC1-expressing breast cancer and 2 ovarian cancer cell lines and with a MUC1-gene-transfected Chinese hamster ovary cell line. The reactivity of VU-2-G7 was always higher than that of VU-4-H5, raised against a nonglycosylated 60-mer MUC1 triple tandem repeat peptide. Immunohistochemical staining of paraffin sections of breast and ovarian tumor tissues showed strong binding of VU-2-G7 predominantly at the cell membrane. The dominant epitope of VU-2-G7 is in the glycosylated PDTR motif of the MUC1 tandem repeat, and this epitope is abundantly present on the surface of tumor cell lines and breast and ovarian tumor tissues. Given the ubiquitously aberrant glycosylation of MUC1 in malignant cells, the production of MAbs against highly purified glycosylated MUC1 tandem repeat peptides may yield MAbs better suited for the immunotherapy of carcinomas than those available at the moment.

Intra-arterial neoadjuvant chemotherapy followed by radical surgery and radiotherapy for stage IIb cervical carcinoma.

BACKGROUND: The role of intra-arterial neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma has not been established. The aim of this study was to determine whether pre-operative intra-arterial NAC is effective or not in patients with stage IIb cervical carcinoma. PATIENTS AND METHODS: A total of 28 patients with stage IIb cervical carcinoma (diameter > 4 cm) were treated with one cycle of intra-arterial NAC (cisplatin 70 mg/m2, and peplomycin sulfate 30 mg/m2 or doxorubicin 30 mg/m2) followed by radical surgery and post-operative radiotherapy. Immediate response, toxicity, survival, and prognostic factors for survival were evaluated. RESULTS: The overall clinical response rate was 79% (22/28) with a complete response in 1 patient (4%). Radical hysterectomy with pelvic lymphadenectomy was feasible in 25 patients (89%) 4 weeks after chemotherapy. Toxicity were generally mild, and there were no intraoperative complications related to intra-arterial NAC. The estimated 2- and 5-year survival rates for the entire group were 93% and 80%, respectively, with a median followup time in survivors of 62 months. Univariate analysis showed the following to be significantly related to survival: histologic type, PCNA index, clinical response to intraarterial NAC, and lymph node metastasis. Survival was not significantly related to age, grade of differentiation, serum level of squamous cell carcinoma antigen, p53 protein expression, or residual parametrial involvement. Multivariate Cox's proportional hazard analysis showed that only the histologic type significantly influenced survival (p = 0.0007). The estimated 2- and 5-year survival rates were 100% and 94% for patients with squamous cell carcinoma, and 75% and 50% for those with adenocarcinoma. CONCLUSIONS: Intra-arterial NAC followed by surgery and radiotherapy appeared to be effective in treating patients with stage IIb cervical squamous cell carcinoma, but was not as effective in patients with stage IIb cervical adenocarcinoma.

Cardiac output measurement by thoracic electrical bioimpedance in a patient with ovarian hyperstimulation syndrome.

A 31-year-old woman developed severe ovarian hyperstimulation syndrome (OHSS) after exogenous gonadotropin stimulation for an in vitro fertilization program. Because of refusal of invasive monitoring, thoracic electrical bioimpedance (TEB) was performed to evaluate cardiac function and volume status. TEB pointed out decreased cardiac output (CO: 4.23 liters/min), cardiac index (CI: 2.63) and stroke volume (SV: 57.5 ml/beat). Serial monitoring of hemodynamic variables was then performed. After the data were obtained, fluid management was performed, and the patient recovered from abnormal homeostasis in 3 days. The hemodynamic variables returned to the normal range (CO: 6.85 liters/min, CI: 4.25, SV: 100.5 ml/beat) within the first 24 h. There were no complications such as life-threatening multiple organ failure. We discuss the usefulness of TEB for the fluid management of severe OHSS, as well as its implications.

Rare case of transitional cell carcinoma originating in Bartholin's gland duct.

We report a rare case of papillary invasive transitional cell carcinoma (TCC) that originated in Bartholin's gland duct. It resulted in differentiation into low-grade dysplasia and grade-III invasive TCC. Because invasive lesions within the lamina propria developed from flat dysplasia, the invasive TCC had presumably progressed from low-grade dysplasia. To our knowledge, 6 cases of TCC originating in Bartholin's gland have been reported previously, but our report is the first to describe TCC associated with dysplasia. The progressive course of this rare carcinoma is discussed.

Primary clear cell adenocarcinoma of the fallopian tube with brain metastasis: a case report.

The first reported case of cerebellar metastasis from primary clear cell adenocarcinoma of the fallopian tube is presented. Initially diagnosed as stage Ia, the patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy, followed by cisplatin-based chemotherapy and whole pelvic irradiation. Thirty six months later multiple pulmonary metastases were detected that did not respond to chemotherapy. Later the patient presented with cerebellar metastasis. She received whole brain radiotherapy and steroids. The brain lesion partially responded and the patient's neurologic symptoms improved. Throughout there was no evidence of local recurrence. This case suggests that with the prolonged survival achieved by aggressive treatment occult brain metastases might become apparent.

Immunohistochemical evaluation of sialosyl-Tn antigens in various ovarian carcinomas.

Sialosyl-Tn (S-Tn) antigen, a cancer-related antigen, was expressed in 56.3% (36 of 64 cases) of the common epithelial carcinoma tissues. This antigen was moderately to strongly expressed in 83.3% (15 of 18 cases) of the mucinous adenocarcinomas. In contrast, it was weakly expressed in 31.3% (5 of 16 cases) of the serous adenocarcinomas. Expression of this antigen in ovarian mucinous tumors of borderline malignancy was 80% (4 of 5 cases), and the staining was moderately intense. S-Tn reactivity was found in 11.5% (3 of 26 cases) of benign ovarian neoplasms. The S-Tn antigen was not found in either normal ovarian tissues or the normal vaginal squamous epithelia. We conclude that the S-Tn antigen may be useful in the histological classification of ovarian carcinomas and in the determination of the malignant potential of such lesions. Moreover, because increases in serum S-Tn antigen were often accompanied by its positive expression in tumor tissues, the S-Tn antigen appears to be a tumor marker in sera with a high specificity for ovarian carcinoma, particularly mucinous adenocarcinoma.

Morular metaplasia of the endometrium in a patient with polycystic ovary syndrome.

A 31-year-old women with polycystic ovary syndrome underwent dilatation and curettage (D&C) as part of her infertility workup. Pathologic examination revealed endometrial morular metaplasia without malignant potential. Follow-up D&C had no evidence of endometrial hyperplasia or carcinoma. The diagnostic difficulties and pathogenesis are discussed.

Endosalpingiosis in association with ovarian surface papillary tumor of borderline malignancy.

A 40-year-old woman underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and omentectomy for Stage IA ovarian surface papillary tumor of borderline malignancy. Microscopic examination revealed endosalpingiosis of ovaries, the peritoneum of uterus, pelvic lymph nodes, and omentum. There was no evidence of disseminated peritoneal malignancy. The several proposed theories of the pathogenesis of endosalpingiosis are reviewed, but that involving metaplasia of the multipotential peritoneal cells is presented as the most acceptable.

Basic evaluation of an immunoradiometric competitive inhibition assay for sialosyl-Tn antigen in sera in women. Assay conditions and normal values.

The assay conditions needed for an immunoradiometric competitive inhibition assay of sera in healthy women were studied using the monoclonal antibody TKH2, which is known to recognize specifically sialosyl-alpha 2,6-GalNAc alpha 1-0-serine/threonine (S-Tn) antigen, a mucinous cancer-related antigen. Stable results were obtained with an incubation time of 1.5 hours at room temperature. The intra-assay and inter-assay coefficients of variation were 3.27% and 3.07%, respectively. The mean (+/- standard deviation [SD]) levels of serum S-Tn in 602 healthy women was 21.2 U/ml (+/- 8.4 U/ml). Values showed a normal logarithmic distribution. Although slightly higher levels were seen in postmenopausal compared with premenopausal women, the differences were not significant. The cutoff value of 41 U/ml was determined from data obtained in 602 healthy women; higher levels were observed in only 2%. Serum S-Tn levels were not strongly influenced by Lewis or ABO (H) blood type, smoking, pregnancy, parturition, or phase of menstrual cycle. The use of the S-Tn antigen as a tumor marker for various gynecologic cancers requires study.

Clinical evaluation of serum sialosyl-Tn antigen levels in comparison with CA 125 levels in gynecologic cancers.

The serum levels of sialosyl-alpha 2,6GalNAc alpha 1-0-serine/threonine (S-Tn) antigen and CA 125 antigen were measured in 205 patients with gynecologic tumors, including 48 ovarian cancers, 20 endometrial cancers, 29 cervical cancers, 57 benign ovarian tumors, 37 uterine leiomyomas, and 14 adenomyosis. Using a cutoff value of 41 U/ml for S-Tn and 35 U/ml for CA 125, positive findings were obtained in ovarian cancers in 31 of 48 (64.6%) patients with S-Tn antigen, and in 36 of 48 (75%) patients with CA 125. In uterine malignancies, positive findings were obtained in 11 of 49 (22.4%) patients and in 8 of 49 (16.3%) patients with the serum S-Tn and CA 125 antigens, respectively. In ovarian benign tumors, false-positive findings with CA 125 were observed in 16 of 57 (28.1%) patients, but with S-TN antigen in only 3 of 57 (5.3%) patients (P less than 0.01). For the ovarian tumors, excluding patients with recurrent disease, the specificity, positive predictive value, and accuracy of the serum S-Tn antigen level for detecting cancer exceeded that of the serum CA 125. The combined assay of serum S-Tn and CA 125 antigens gave positive results in 38 of 48 (79.2%) patients with ovarian cancers; most of the negative findings were obtained in Stage I disease. A significant decreases in serum S-Tn level was observed after cytoreductive surgery in 14 patients with ovarian cancer (P less than 0.01). Four patients with a subsequent recurrence showed a concomitant rise in serum S-Tn. The cyst fluid and ascitic fluid showed high levels of S-Tn antigen in patients with ovarian cancer, in contrast to findings in patients with benign ovarian tumors. In conclusion, serum S-Tn antigen has limited use in diagnosing early stage ovarian cancer and uterine malignancies, but it can detect with accuracy ovarian cancers when used in a combination assay with CA 125 and can monitor the status of disease after therapy.

[Intraperitoneal chemotherapy through implantable injection port in patients with advanced ovarian (or tubal) carcinoma].

A total of 38 cycles of intraperitoneal chemotherapy through implantable injection port were carried out in 9 patients with advanced or recurrent ovarian (tubal) carcinoma. The combination chemotherapy consisted of cisplatin 100 mg or carboplatin 450 mg, 5-FU 500 mg and OK-432 10 KE was administered every four weeks for a total of six cycles. Clinical response was evaluated after chemotherapy. Of the eight evaluated patients (in one patient chemotherapy is not completed yet), 1 had complete response, 3 partial response, 2 stable disease and 2 progressive disease. Therapy-related toxic effects were moderate, consisting chiefly of myelosuppression that seemed dose limiting.

[The cytoimmunological effect of concomitant use of sizofiran (SPG) on advanced uterine cervical cancer treated with radiation].

The immunological effect has been studied of the non-specific immunopotentiator sizofiran (SPG) on patients with advanced uterine cervical cancer treated with radiation. Ten cases (study group: SPG group) were administered weekly 40 mg of SPG throughout the course of radiation and two weekly 40 mg during 12 months after radiotherapy. Nineteen cases (control group) were treated with irradiation alone. The lymphocyte count, the PHA index and the ratio of CD4 cells/CD8 cells were significantly reduced by radiotherapy, being observed the most remarkable decrease at post-radiotherapy. But in SPG group, these decreasing values were significantly smaller than in control group and the values showed a more progressive rise during the 12 month respectively. There was no significant difference in peripheral T lymphocyte; CD3, CD4, CD8. The NK cytotoxic activity showed a progressive rise during the 12 month period following a minimal change after radiotherapy. These results suggest that the SPG have some enhancing effect on the function of the lymphocytes.