Anti-EJ antibody-positive interstitial pneumonia with breast cancer improved by combining immunosuppressive therapy and chemotherapy.

We present a case of a 45-year-old woman diagnosed with interstitial pneumonia (IP) during a comprehensive breast cancer evaluation. Although the patient showed no obvious clinical symptoms of polymyositis or dermatomyositis, the presence of anti-glycyl-transfer ribonucleic acid synthetase antibodies confirmed anti-synthetase syndrome. The patient began methylprednisolone for treatment of the IP. She then received preoperative chemotherapy with epirubicin and cyclophosphamide before undergoing a mastectomy. A significant improvement was seen in the patient's IP during treatment. This case emphasizes the potential advantages of personalized immunosuppressive therapy for patients who are simultaneously diagnosed with anti-synthetase syndrome and cancer.

[Evaluation of Patient Adherence to Anastrozole Therapy for Breast Cancer].

PURPOSE: There are many reports that describe the effectiveness of aromatase inhibitors as endocrine therapy after breast cancer surgery. However, there are few detailed evaluations of patient adherence to anastrozole(ANA)therapy. Here, we evaluated the adherence to ANA therapy in postoperative patients with primary breast cancer. METHODS: We investigated 102 postoperative patients with primary breast cancer without distant metastasis, who received ANA at JCHO Kyusyu Hospital. We calculated the medication continuation rate and disease-free survival at 5 years from the initiation of medication. The reasons for medication discontinuation and alternative drug therapy after ANA therapy discontinuation were also investigated. Re- sults: The 5-year continuation rate of ANA treatment alone was 79%(81/102). The rate of all patients who continued ANA treatment, including 9 who changed to other drugs, was 88%(90/102). The most frequent ANA discontinuation reasons were progressive disease(8 cases), arthritis(5 cases), and nausea(3 cases). The disease-free survival rate was 92%(94/102), and the overall survival rate was 97%(99/102). CONCLUSION: ANA showed a high continuation rate. Adherence of ANA in postoperative patients with breast cancer was well maintained, even when the treatment was changed to other drugs due to adverse events.

[A case of squamous cell carcinoma of the nipple skin successfully treated with S-1 alone].

Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is rarer. The effect of chemotherapy in these cases is yet to reach consensus. We report a rare case in which primary squamous cell carcinoma of the nipple skin was successfully treated with S-1 alone. A 64-year-old woman was admitted to our hospital because of a granulomatous tumor mass over the right nipple, which she was aware of for 10 years; the tumor showed a rapid increase in growth before admission. The tumor was approximately 4 cm at the first visit, and was diagnosed as squamous cell carcinoma by incisional biopsy. We administered preoperative systemic chemotherapy owing to the presence of metastasis in an axillary lymph node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days followed by a 14-day resting period, the primary tumor and metastatic lymph node showed a remarkable reduction in size. The patient subsequently underwent a radical operation and is currently healthy without any recurrence.

Short-term and low-dose prednisolone administration reduces aromatase inhibitor-induced arthralgia in patients with breast cancer.

Aromatase inhibitors (AIs) are important therapeutic drugs for postmenopausal women with hormone receptor-positive breast cancer. However, adverse effects of AIs such as arthralgia have been extensively reported. We performed a joint prospective, multi-institutional investigation to find out whether a low-dose and short-term prednisolone is effective against AI-induced arthralgia in 27 patients with breast cancer. Patients were administered 5 mg of oral prednisolone once a day in the morning for only one week. Patients were then asked to answer a questionnaire about joint pain symptoms at one week, one month and two months after the beginning of prednisolone use. Joint pain symptoms improved in 67% of patients immediately after prednisolone use, with 63% still reporting analgesic effect at one month, and 52% at two months after beginning internal use of prednisolone. At one week, one month and two months after the use of prednisolone, 30%, 30% and 26% of patients reported improved daily life, respectively. Our results suggest that prednisolone could substitute non-steroidal anti-inflammatory drugs, acetoaminophen or cyclooxygenase-2 inhibitors in patients with AI-induced arthralgia.

[Chemotherapy for non-small cell lung cancer: split-dose administration of Cisplatin over four consecutive days and Vinorelbine ditartrate].

PURPOSE: At present, combination chemotherapy with Cisplatin (CDDP) and Vinorelbine ditartrate (VNR) is one of the standard regimens for non-small cell lung cancer (NSLC). To avoid renal damage by CDDP, hydration and diuretic are indicated. But elderly/postoperative patients who have reduced lung vessel capacity are a high-risk group for pulmonary edema/right heart failure by hydration. In our hospital, CDDP is administered on four consecutive days without large hydration. MATERIAL & METHODS: CDDP: 80 mg/m2 (over four consecutive days)without large hydration+VNR: 20 mg/m2 was administered 30 NSLC patients(Stage III A & IV). Serum concentration of CDDP was monitored. RESULT: Response rate was CR: 0 case; PR: 9 cases; SD: 16 cases; PD: 5 cases. Mean survival time (MST) was 292 days. The efficacy and prognosis are equivalent to a conventional CDDP+VNR regimen. On the other hand, side effects were reduced; neutrocytopenia (> Grade 3): 17%, renal dysfunction (>Grade 1): 17%. Mean serum concentrations of CDDP were accumulated day by day, 0.91 microg/mL(Day 1), 2.44 microg/mL(Day 4), but were all under the toxic threshold(8 microg/mL). CONCLUSION: Our regimen (CDDP given over four consecutive days without large hydration) may become a regimen for the high-risk patient.

Simple methodology for detecting time shifts in surgical site infections: a study in digestive, breast, and thoracic surgery.

To simplify the data mining surveillance system for the monitoring of surgical site infections (SSIs), electronic analysis of a total of 3100 patients was done. Using Layered Analyses, the Cross-Table option of a globally available software detected emerging or disappearing SSIs according to specific parameters. This methodology may facilitate the detection of SSI shifts.

Mammalian mitochondrial endonuclease G. Digestion of R-loops and localization in intermembrane space.

Mammalian mitochondria contain strong nuclease activity. Endonuclease G (endoG), which predominantly resides in mitochondria, accounts for a large part of this nuclease activity. It has been proposed to act as an RNase H-like nuclease on RNA.DNA hybrids (R-loops) in the D-loop region where the origins of mitochondrial replication are mapped, providing RNA primers for mtDNA replication. However, in contrast with this proposed activity, endoG has recently been shown to translocate to nuclei on apoptotic stimulation and act as a nuclease without sequence specificity. To clarify the role of endoG in mtDNA replication, we examined its submitochondrial localization and its ability to cleave R-loops. At low concentration, it preferentially produces double-stranded breaks in R-loops, but does not act as an RNase H-like nuclease. In addition, it exists in the mitochondrial intermembrane space, but not in the matrix where mtDNA replication occurs. These results do not support the involvement of endoG in mtDNA replication. Based on the fact that guanine tracts, which are preferential targets of endoG, tend to form triplex structures and that endoG produces double-stranded breaks in R-loops, we propose that three-stranded DNA may be the preferred substrate of endoG.

1-Methyl-4-phenylpyridinium ion, a toxin that can cause parkinsonism, alters branched structures of DNA.

During replication, human mitochondrial DNA (mtDNA) takes on a triple-stranded structure known as a D-loop, which is implicated in replication and transcription. 1-Methyl-4-phenylpyridinium ion (MPP+), a toxin inducing parkinsonism, inhibits mtDNA replication, possibly by resolving the D-loops. For initiation of mtDNA replication, mitochondria are thought to have another triple-stranded structure, an R-loop. The R-loop, which is resolved by a bacterial junction-specific helicase, RecG, is also resolved by MPP+. Because mitochondrial D-loops are likewise resolved by RecG, the D- and R-loops may share a similar branched structure. MPP+ resolves cruciform DNA in supercoiled DNA. MPP+ converts a stacked conformation to an extended conformation in a synthetic Holliday junction. This conversion is reversed by 1 mM Mg(2+), as is the resolution of the D-loops or cruciform DNA. These observations suggest that the junction structure of mitochondrial D- and R-loops is affected by MPP+.

Regulation of mitochondrial D-loops by transcription factor A and single-stranded DNA-binding protein.

During replication, mitochondrial DNA (mtDNA) takes on a triple-stranded structure called a D-loop. Although their physiological roles are not understood, D-loops are implicated in replication and transcription of mtDNA. Little is known about the turnover of D-loops. We investigated the effects of mitochondrial transcription factor A (TFAM) and single-stranded DNA-binding protein (mtSSB) on D-loops. In human HeLa cells, TFAM and mtSSB are, respectively, 1700- and 3000-fold more abundant than mtDNA. This level of TFAM is two orders of magnitude higher than reported previously and is sufficient to wrap human mtDNA entirely. TFAM resolves D-loops in vitro if added in similar stoichiometries. mtSSB inhibits the resolution of mtDNA by TFAM but enhances resolution by RecG, a junction-specific helicase from Escherichia coli. Hence, mtSSB functions in both stabilization and resolution. We propose that TFAM and mtSSB are cooperatively involved in stabilizing D-loops and in the maintenance of mtDNA.