[A Case of Disseminated Myelocarcinoma with Bone Metastasis 15 Years after Mastectomy and Relatively Long-Term Survival through Multidisciplinary Treatment].

The patient was a 62-year-old woman who had undergone mastectomy in August 2003 for cancer of the right breast. In addition to radiation therapy in the remaining breast, chemotherapy and endocrine therapy were subsequently performed. The patient had a 10-year recurrence-free postoperative course followed by annual surveillance. Beginning in 2016, an elevation in the serum level of tumor markers was detected; however, no accumulations were found in PET-CT over 2 consecutive years(2016 and 2017). Thereafter, serum levels of tumor markers continued to rise, and a PET-CT in 2018 revealed costal accumulations leading to a diagnosis of late-stage bone metastasis in postoperative year 15. Although hormone therapy was resumed, a continuing rise in the serum level of tumor markers led to a diagnosis of diffuse bone metastasis by MRI in 2019. Treatment with abemaciclib was initiated, and with effective radiotherapy, the PS was maintained at 0-1, serum levels of tumor markers decreased, and the lesions themselves continued at SD. However, in June 2020, multiple liver metastases appeared in an abdominothoracic CT scan. The patient refused chemotherapy; this, a BSC policy was adopted. Acute hemolytic anemia occurred immediately thereafter, and the PS gradually deteriorated. The patient died in September 2020, 17 years and 1 month after surgery.

New phenylspirodrimane metabolites MBJ-0030, MBJ-0031, and MBJ-0032 isolated from the soil fungal strain Stachybotrys sp. f23793.

Chemical screening of culture medium from the soil fungus Stachybotrys sp. resulted in the isolation of the three new phenylspirodrimanes MBJ-0030 (1), MBJ-0031 (2) and MBJ-0032 (3). Their structures were determined by detailed analysis of spectroscopic data. The absolute configurations of 1-3 were determined by modified Mosher's and Marfey's methods. In addition, cytotoxic and antimicrobial evaluations of the compounds were conducted.

Regioselective biooxidation of (+)-valencene by recombinant E. coli expressing CYP109B1 from Bacillus subtilis in a two-liquid-phase system.

BACKGROUND: (+)-Nootkatone (4) is a high added-value compound found in grapefruit juice. Allylic oxidation of the sesquiterpene (+)-valencene (1) provides an attractive route to this sought-after flavoring. So far, chemical methods to produce (+)-nootkatone (4) from (+)-valencene (1) involve unsafe toxic compounds, whereas several biotechnological approaches applied yield large amounts of undesirable byproducts. In the present work 125 cytochrome P450 enzymes from bacteria were tested for regioselective oxidation of (+)-valencene (1) at allylic C2-position to produce (+)-nootkatone (4) via cis- (2) or trans-nootkatol (3). The P450 activity was supported by the co-expression of putidaredoxin reductase (PdR) and putidaredoxin (Pdx) from Pseudomonas putida in Escherichia coli. RESULTS: Addressing the whole-cell system, the cytochrome CYP109B1 from Bacillus subtilis was found to catalyze the oxidation of (+)-valencene (1) yielding nootkatol (2 and 3) and (+)-nootkatone (4). However, when the in vivo biooxidation of (+)-valencene (1) with CYP109B1 was carried out in an aqueous milieu, a number of undesired multi-oxygenated products has also been observed accounting for approximately 35% of the total product. The formation of these byproducts was significantly reduced when aqueous-organic two-liquid-phase systems with four water immiscible organic solvents - isooctane, n-octane, dodecane or hexadecane - were set up, resulting in accumulation of nootkatol (2 and 3) and (+)-nootkatone (4) of up to 97% of the total product. The best productivity of 120 mg l-1 of desired products was achieved within 8 h in the system comprising 10% dodecane. CONCLUSION: This study demonstrates that the identification of new P450s capable of producing valuable compounds can basically be achieved by screening of recombinant P450 libraries. The biphasic reaction system described in this work presents an attractive way for the production of (+)-nootkatone (4), as it is safe and can easily be controlled and scaled up.

[Stereotactic hypofractionated radiotherapy of non-hepatic abdominal tumors].

PURPOSE: The clinical experiences of 12 patients with non-hepatic abdominal tumors who underwent stereotactic hypofractionated radiotherapy are presented. METHODS AND MATERIALS: Ten lesions were metastatic, one was a primary pancreatic cancer, and the remaining one was irradiated postoperatively for a positive margin of extrahepatic bile duct cancer. In one patient, single fractional stereotactic radiotherapy was employed, while the remaining 11 patients were treated with 3 fractions. Gross tumor volume of the 10 ranged from 2 cc to 32 cc (mean: 11 cc), and the minimal dose enclosing 95% of the planning target volume (D95) was between 28.6 Gy and 35 Gy. The minimal number of portals was 6. In 8 patients, radiotherapy was performed under respiratory gating. Mean follow-up time was 10 months (5-51 months). RESULTS: Local regrowth was seen in 9 months in only 1 of the 12 tumors, and the patient died of the disease. Four patients died because of tumor growth in other sites. The remaining 7 patients are alive without disease. As for morbidity, NCI-CTC grade 3 gastritis was seen in one patient, grade 2 gastritis in 2 patients, and grade 2 duodenitis in one patient. These patients all improved with non-surgical therapy. CONCLUSION: Stereotactic hypofractionated radiotherapy is effective for the treatment of selected non-hepatic abdominal tumors. However, the optimal radiation dose for tumor control and the tolerance dose of the gastrointestinal tract in hypofractionated irradiation must be studied further.