Mechanistic insights into structure-based design of a Lyme disease subunit vaccine.

The quality of protective immunity plays a critical role in modulating vaccine efficacy, with native antigens often not able to trigger sufficiently strong immune responses for pathogen killing. This warrants creation of structure-based vaccine design, leveraging high-resolution antigen structures for mutagenesis to improve protein stability and efficient immunization strategies. Here, we investigated the mechanisms underlying structure-based vaccine design using CspZ-YA, a vaccine antigen from , the bacteria causing Lyme disease (LD), the most common vector-borne disease in the Northern Hemisphere.

Microbial genetic variation impacts host eco-immunological strategies and microparasite fitness in Lyme borreliae-reptile system.

Tolerance and resistance are two host eco-immunological strategies in response to microparasite invasion. In the strategy of "resistance", host responses are induced to decrease microparasite replication while the "tolerance" strategy allows hosts coexistence with microparasites by minimizing responses to avoid immune-mediated damage. The causative agent of Lyme disease is a group of genotypically diverse bacterial species, Borrelia burgdorferi sensu lato (Bb), which is transmitted by Ixodes ticks and persists in different reservoir animals.

Whole abdominal radiotherapy in the adjuvant treatment of patients with stage III and IV endometrial cancer: a gynecologic oncology group study.

Objective: To evaluate toxicity, survival, and recurrence-free interval in women with loco-regionally advanced endometrial carcinoma treated with postoperative whole abdominal radiation therapy.

Methods: Whole abdominal irradiation with pelvic plus or minus para-aortic boost was initiated within 8 weeks of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and selective pelvic and para-aortic node sampling in eligible, consenting patients.

Results: Of 180 evaluable patients entered on the study with surgically staged III and IV endometrial carcinoma maximally debulked to less than 2 cm, 77 had typical endometrial adenocarcinoma and 103 had high-risk histology, either papillary serous or clear cell carcinoma.

Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a gynecologic oncology group study.

Purpose: Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone.

Patients And Methods: Of 299 patients registered, 281 (94%) were eligible.

Vulvar malignant melanoma associated with human papillomavirus DNA: report of two cases and review of literature.

Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown. We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin.

Possible mechanisms of hypopigmentation in lichen sclerosus.

Lichen sclerosus (LS) shares with vitiligo a milky-white appearance. By biopsy, pathognomonic dermal sclerosis readily distinguishes LS from vitiligo and other causes of leukoderma. To determine what the mechanism of hypopigmentation is in LS, we examined samples from LS cases for alterations in melanin content (Fontana-Masson stain) and melanocyte number (HMB-45 [PMEL-17/gp100], Mel-5 [TRP-1], Mart-1 [Melan A]) and compared these findings with those in controls of normal skin, acute scars, vitiligo, and lichen planus (LP; a common inflammatory cause of hyperpigmentation).

Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the uterus: a gynecologic oncology group study.

Objectives: This is a Phase II group-wide study of the Gynecologic Oncology Group to determine the toxicity and objective response rate of trimetrexate (TMTX) in patients with advanced, persistent, or recurrent mixed mesodermal tumors of the uterus who have failed higher priority treatment protocols.

Methods: TMTX was administered orally at a dose of 5 mg/m(2) BID for 5 days and repeated in 14 days. The maximum total dose was 50 mg/m(2)/week given every other week.

Melanocytic proliferations associated with lichen sclerosus.

Objectives: To describe the clinicopathologic features of melanocytic proliferations associated with lichen sclerosus (LS) and to compare these findings with those in controls.

Design: Cohort study.

Setting: Academic and private practice dermatology and dermatopathology services.

A randomised trial of oral versus intravenous topotecan in patients with relapsed epithelial ovarian cancer.

A multicentre, randomised study was carried out in Europe, South Africa and North America to compare the activity and tolerability of oral versus intravenous (i.v.) topotecan in patients with relapsed epithelial ovarian cancer.

Oral topotecan as single-agent second-line chemotherapy in patients with advanced ovarian cancer.

Purpose: To evaluate oral topotecan as single-agent, second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen.

Patients And Methods: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days.

Decreased CD44 standard form expression correlates with prognostic variables in ovarian carcinomas.

Expression of CD44 standard form (CD44s) was evaluated by automated immunohistochemical analysis using the anti-CD44 A3D8 clone in 101 ovarian epithelial neoplasms including 82 primary tumors (64 carcinomas and 18 tumors of low malignant potential [LMP]), 9 lymph node metastases, 8 malignant ascites, and 2 peritoneal implants. Immunostaining was scored semiquantitatively. Tumors were graded according to the FIGO (International Federation of Gynecology and Obstetrics) classification system.

Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus.

To determine if carcinogenic events in vulvar skin precede the onset of morphologic atypia, the authors investigated for derangements in DNA content, cell proliferation, and cell death in vulvar carcinomas and surrounding skin in 140 samples of tumor and surrounding skin collected from 35 consecutive vulvectomy specimen for squamous cell carcinoma (SCC) or vulvar intraepithelial neoplasia (VIN) 3. Vulvar non-cancer excisions were used as controls. Investigations consisted of histologic classification and measurement of 9 variables--epidermal thickness (acanthosis and rete ridge length), immunolabeling index (LI) for 3 proteins (p53 protein, Ki-67, and mdm-2), pattern of p53 expression (dispersed vs.

Clinical evidence for topotecan-paclitaxel non--cross-resistance in ovarian cancer.

Purpose: A large, randomized study comparing the efficacy and safety of topotecan versus paclitaxel in patients with relapsed epithelial ovarian cancer showed that these two compounds have similar activity. In this study, a number of patients crossed over to the alternative drug as third-line therapy, ie, from paclitaxel to topotecan and vice versa. We therefore were able to assess the degree of non-cross-resistance between these two compounds.

Paclitaxel, an active agent in nonsquamous carcinomas of the uterine cervix: a Gynecologic Oncology Group Study.

Purpose: A phase II trial of paclitaxel was initiated in advanced nonsquamous carcinoma of the cervix to determine its activity in patients who had failed standard chemotherapy.

Patients And Methods: Eligible patients had at least one measurable lesion. The starting dose of paclitaxel was 170 mg/m(2) (135 mg/m(2) for patients with prior pelvic radiation) given as a 24-hour continuous intravenous infusion with courses repeated every 3 weeks.

Chromosome 17 aneusomy detected by fluorescence in situ hybridization in vulvar squamous cell carcinomas and synchronous vulvar skin.

Vulvar squamous cell carcinoma (SCC) affects a spectrum of women with granulomatous vulvar diseases, human papillomavirus (HPV) infections, and chronic inflammatory vulvar dermatoses. To determine whether there is evidence of chromosomal instability occurring in synchronous skin surrounding vulvar SCCs, we investigated abnormalities in chromosome 17 copy number. Samples of SCC, vulvar intraepithelial neoplasia (VIN), and surrounding vulvar skin were obtained from all vulvar excisions performed for squamous neoplasia at Albany Medical College from 1996 to 1997.

Comparative immunophenotypic study of lichen sclerosus: epidermotropic CD57+ lymphocytes are numerous--implications for pathogenesis.

To characterize the immunophenotype of inflammatory cells in lichen sclerosus (LS), we performed a comparative case control study using one- and two-color immunohistochemistry and the nitro blue tetrazolium (NBT) reaction. Study material consisted of 100 biopsies from patients with LS or from 12 control groups consisting of inflammatory, scarring, and depigmenting cutaneous disorders. In addition, fresh tissue was sampled from four vulvectomy specimens for NBT testing.

Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study.

Purpose: In 1986, a protocol comparing primary radiation therapy (RT) plus hydroxyurea (HU) to irradiation plus fluorouracil (5-FU) and cisplatin (CF) was activated by the Gynecologic Oncology Group (GOG) for the treatment of patients with locally advanced cervical carcinoma. The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities.

Methods: All patients had biopsy-proven invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix.

Cell proliferation-associated proteins in endometrial carcinomas, including papillary serous and endometrioid subtypes.

Cyclin dependent kinases (cdks) and cyclins regulate the progression of cells through the cell cycle and can be overexpressed in human cancers. The purpose of this study was to evaluate the immunohistochemical profile of these proliferation-associated proteins and correlate the results with clinicopathologic parameters of endometrial carcinomas. Archival tissue sections from 91 endometrial carcinomas were immunostained using monoclonal antibodies against p34CDC2 cdk, cyclins A and B1, p120, Ki-67, and PCNA.

Clinicopathologic comparison of vulvar and extragenital lichen sclerosus: histologic variants, evolving lesions, and etiology of 141 cases.

Lichen sclerosus (LS) is a persistent inflammatory dermatosis of unknown etiology with a predilection for the vulva, where it is a risk factor for carcinoma. We performed a clinicopathologic study on 121 cases of vulvar LS and 20 of extragenital LS, and we reviewed 49 vulvectomy specimens with LS to define morphologic findings, identify the earliest lesions, and correlate outcomes with histologic findings. The vulvar LS lesions were pruritic/burning, white/red, ill-defined patches predominately affecting the labia, perineum, introitus, and perianal region.

Vulvar lichen sclerosus and squamous cell carcinoma: a cohort, case control, and investigational study with historical perspective; implications for chronic inflammation and sclerosis in the development of neoplasia.

The histological changes of lichen sclerosus (LS) are frequently found in association with vulvar squamous cell carcinoma (SCC). The importance of chronic inflammation and scarring in oncogenesis is well recognized. Thirty-two patients with symptomatic vulvar LS and 60 with vulvar SCC were studied.

Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies.

This combined analysis investigated the effect of marimastat, a specific inhibitor of matrix metalloproteinases, on markers of tumor progression measured in patients with advanced cancer. By defining the tolerability and biological activity of the drug, it aimed to establish an appropriate dose range for use in Phase III trials. Patients with advanced, serologically progressive ovarian, prostatic, pancreatic, and colorectal cancer were recruited into six nonrandomized, dose ranging, multicenter clinical trials in North America and Europe.

Amonafide in patients with leiomyosarcoma of the uterus: a phase II Gynecologic Oncology Group study.

Twenty-six evaluable patients who had leiomyosarcoma of the uterus were treated with amonafide, 300 mg/m2, for 5 consecutive days every 3 weeks. One partial response (4%) resulted. Hematologic toxicity was substantial, with grade 3 or 4 events occurring as follows: leukopenia, 12 patients (46%); thrombocytopenia, 4 patients (15%); and granulocytopenia, 7 patients (27%).

Extended field radiation and cisplatin for stage IIB and IIIB cervical carcinoma.

Objective: The aim of this study was to investigate local regional control, survival, and morbidity in patients with FIGO IIB and IIIB squamous cell carcinoma of the cervix treated with primary extended field (prophylactic paraaoratic radiation) radiation and weekly cisplatin.

Methods: Sixty-seven patients (44 IIB and 23 IIIB) with carcinoma of the cervix received cisplatin at 1 mg/kg (up to 60 mg) weekly and extended field radiation therapy including the paraaortic nodes and brachytherapy.

Results: After the scheduled therapy 94.