Design, synthesis, and bio-evaluation of novel triterpenoid derivatives as anti-HIV-1 compounds.

Two betulinic acid derivatives, RPR103611 (2) and IC9564 (3) were previously reported to be potent HIV-1 entry inhibitors. In this current study, a SAR study of the triterpenoid moiety of 2 and 3 has been performed and an oleanolic acid derivative (4) was identified as a novel HIV-1 entry inhibitor. In addition, the combination of 4 with several-type of HIV-1 neutralizing antibodies provided significant synergistic effects. The synthetic utility of the CC double bond in the C-ring of 4 was also demonstrated to develop the 12-keto-type oleanolic acid derivative (5) as a potent anti-HIV compound. This simple transformation led to a significantly increased anti-HIV activity and a reduced cytotoxicity of the compound.

[Long-Term Survival of a Patient with Triple-Negative Breast Cancer with Hormone Receptor Status Conversion between Primary and Metastatic Tumors].

Patients with triple-negative breast cancer have poor survival after recurrence. However, previous studies have shown that receptor conversion can occur between primary breast tumor and metastatic sites. Herein, we describe the case of a 54- year-old woman with advanced breast cancer, which showed receptor conversion from primary tumor(triple-negative)to distant metastases(Luminal type). The patient had undergone left radical mastectomy and left axillary lymph node dissection at another hospital(pT3N0M0, Stage ⅡB, ER-negative, PgR-negative, and HER2-negative). She was referred to our hospital for adjuvant chemotherapy with 3 courses of 5-fluorouracil, epirubicin, and cyclophosphamide and 3 courses of docetaxel. Around 26 months after the surgery, the follow-up CT scan showed multiple lung nodules. Another 9 months later, her left axillary and mediastinal lymph nodes were enlarged. She received several courses of anticancer chemotherapy. After paclitaxel and bevacizumab were administered as seventh-line chemotherapy, a vacuum-assisted biopsy of the left axillary lymph node was performed to confirm the presence of metastasis. Furthermore, immunohistochemistry results showed that the metastatic tumor was ER-positive, PgR-positive, and HER2-negative. Fulvestrant and palbociclib were then initiated as first-line endocrine therapy. She has been stable for more than 18 months since. It is essential to perform biopsies of metastatic sites for optimal management of patients with metastatic breast cancer.

Neoadjuvant chemotherapy for primary sarcoma of the breast: a case report.

BACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.