Novel furans and thiophenes, pharmaceutical compositions containing these compounds and their use as endothelin receptor antagonists are described.

Endothelin receptor antagonists

Design and synthesis of Rho kinase inhibitors (I)

Novel compounds of the formula I I in which R1, R2, R3 and X have the meaning indicated in Patent Claim 1, and their salts exhibit endothelin receptor-antagonistic properties.

The endothelin system and its potential as a therapeutic target in cardiovascular disease

Therapeutic vaccination with human papillomavirus type 16 synthetic long peptides (HPV16-SLPs) results in T cell-mediated regression of HPV16-induced premalignant lesions but fails to install clinically effective immunity in patients with HPV16-positive cervical cancer. We explored whether HPV16-SLP vaccination can be combined with standard carboplatin and paclitaxel chemotherapy to improve immunity and which time point would be optimal for vaccination. This was studied in the HPV16 E6/E7-positive TC-1 mouse tumor model and in patients with advanced cervical cancer. In mice and patients, the presence of a progressing tumor was associated with abnormal frequencies of circulating myeloid cells. Treatment of TC-1-bearing mice with chemotherapy and therapeutic vaccination resulted in superior survival and was directly related to a chemotherapy-mediated altered composition of the myeloid cell population in the blood and tumor. Chemotherapy had no effect on tumor-specific T cell responses. In advanced cervical cancer patients, carboplatin-paclitaxel also normalized the abnormal numbers of circulating myeloid cells, and this was associated with increased T cell reactivity to recall antigens. The effect was most pronounced starting 2 weeks after the second cycle of chemotherapy, providing an optimal immunological window for vaccination. This was validated with a single dose of HPV16-SLP vaccine given in this time window. The resulting proliferative HPV16-specific T cell responses were unusually strong and were retained after all cycles of chemotherapy. In conclusion, carboplatin-paclitaxel therapy fosters vigorous vaccine-induced T cell responses when vaccination is given after chemotherapy and has reset the tumor-induced abnormal myeloid cell composition to normal values.

Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses.

https://www.gynecologiconcology-online.net/article/S0090-8258(11)00260-5/pdf

Pretreatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer

Endothelin (ET) is a potent vasoconstrictor/ pressor peptide consisting of 21 amino acid residues isolated from the cultures of porcine aortic endothelial cells1}. Analysis of a human genomic library reveals three forms of ET (ET-1, ET-2 and ET-3) which have more than 70% homology with one another2). In various organs, high affinity and specific receptors for ET have been found3). They have been distinguished as receptors ETA and ETB4-5). ET-1 exhibits potent and long-lasting vasoconstrictive activity in vivo and in vitro1\"1, as a

Asterric acid, a new endothelin binding inhibitor.

Background The use of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is controversial. Methods A total of 103 primary breast cancer patients who were diagnosed with DCIS by needle biopsy preoperatively and underwent initial SLNB were analyzed retrospectively. Results No sentinel nodal metastasis was detected in 66 patients with the final diagnosis of DCIS. However, 2 (5.4%) of 37 patients with invasive ductal carcinoma at final diagnosis had positive sentinel nodes. Multivariate logistic regression analysis identified 2 independent significant predictors of existence of invasive components: presence of a palpable tumor (odds ratio, 4.091; 95% confidential interval, 1.399–11.959; P = .010) and tumor size of 2.0 cm or larger on magnetic resonance imaging (odds ratio, 4.506; 95% confidence interval, 1.322–15.358; P = .016). Conclusions Initial SLNB should be considered for patients diagnosed with DCIS by needle biopsy when they have a high risk for harboring invasive ductal cancer preoperatively.

Indication for sentinel lymph node biopsy for breast cancer when core biopsy shows ductal carcinoma in situ.

Distribution of virginiae butanolides in antibiotic-producing actinomycetes, and identification of the inducing factor from Streptomyces antibioticus as virginiae butanolide A.

Hiroshi Ohashi

Papers

Pretreatment leukocytosis is an indicator of poor prognosis in patients with cervical cancer

Asterric acid, a new endothelin binding inhibitor.

Indication for sentinel lymph node biopsy for breast cancer when core biopsy shows ductal carcinoma in situ.

Distribution of virginiae butanolides in antibiotic-producing actinomycetes, and identification of the inducing factor from Streptomyces antibioticus as virginiae butanolide A.

Sulochrin inhibits eosinophil degranulation.