Usefulness of immediate reconstruction after mastectomy for inflammatory breast cancer with muscle cutaneous flap

CASE 1: A 59-year-old female patient with left inflammatory breast cancer (HER2 type) T4N1M0, stage III B. Although a partial response (PR) was observed after chemotherapy, an increase of the tumor was confirmed, and thus she underwent pectoralis-conserving mastectomy and immediate reconstruction with a rectus abdominis flap. After the surgery, the patient continued to undergo radiotherapy and administration of trastuzumab. At present, after 1 year and 3 months, she is alive with no recurrence. CASE 2: A 67-year-old female patient with left inflammatory breast cancer (triple negative) T4N2M0, stage III B. Since a variety of chemotherapeutics were ineffective, she underwent mastectomy with pectoralis resection and immediate reconstruction with a rectus abdominis flap to control pain/bleeding caused by the increased tumor. Although radiotherapy and chemotherapy were performed after the surgery, lung and hepatic metastases were developed 6 months after the surgery, and she died in the 10th month after the surgery. CONCLUSION: In mastectomy for inflammatory breast cancer, an immediate reconstruction with a muscle cutaneous flap enabled unhesitating mastectomy in a wide area, and thus we consider this will be a useful technique.     

Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo

ZSTK474 is a novel orally applicable phosphoinositide 3‐kinase‐specific inhibitor that strongly inhibits cancer cell proliferation. To further explore the antitumor effect of ZSTK474 for future clinical usage, we studied its combined effects with radiation. The proliferation of HeLa cells was inhibited by treatment with X‐rays alone or ZSTK474 alone. Combination treatment using X‐rays then ZSTK474 given orally for 8 days, starting 24 h post‐irradiation, significantly enhanced cell growth inhibition. The combined effect was also observed for clonogenic survival with continuous ZSTK474 treatment. Western blot analysis showed enhanced phosphorylation of Akt and GSK‐3β by X‐irradiation, whereas phosphorylation was inhibited by ZSTK474 treatment alone. Treatment with ZSTK474 after X‐irradiation also inhibited phosphorylation, and remarkably inhibited xenograft tumor growth. Combined treatment with X‐rays and ZSTK474 has greater therapeutic potential than radiation or drug therapy alone, both in vitro and in vivo. (Cancer Sci 2011; 102: 1176–1180)     

Remnant lipoprotein metabolism is improved more when body weight is reduced by exercise than by dietary restriction

BACKGROUND: Remnant lipoprotein levels during weight-loss programs have not been examined in detail. We investigated the effects of reducing body weight by exercise and by dietary restriction on lipid metabolism including remnant-like particle-cholesterol (RLP-C) and apolipoprotein B48 (apo B48). METHODS: Six adult male volunteers participated in 2 experiments over 10 days. The first 5 days were an adjustment period (energy intake, 2656+/-150 kcal/day; mean+/-SEM). During the second 5 days, the participants either exercised on a bicycle ergometer to consume 886+/-50 kcal/day or reduced their energy intake to 1770+/-100 kcal/day. RESULTS: Serum triglyceride (TG) and RLP-C levels were significantly lower, whereas the increase in high density lipoprotein-cholesterol (HDL-C) level was significantly larger after exercise than after dietary restriction. We measured changes (Delta) in serum levels and identified positive correlations between Delta insulin and Delta TG, Delta apo B48 (p<0.05) and Delta RLP-C (p=0.050) only during exercise. CONCLUSIONS: Reducing body weight by exercise has more beneficial effects on lipid metabolism than a dietary approach, and improved insulin resistance accompanies the decrease of serum remnant lipoprotein levels.     

MMPs initiate Schwann cell-mediated MBP degradation and mechanical nociception after nerve damage

Matrix metalloproteinases (MMPs) emerge as modulators of neuropathic pain. Because myelin protects Aβ afferents from ectopic hyperexcitability and nociception from innocuous mechanical stimuli (or mechanical allodynia), we analyzed the role of MMPs in the development of mechanical allodynia through myelin protein degradation after rat and MMP-9−/− mouse L5 spinal nerve crush (L5 SNC). MMPs were shown to promote selective degradation of myelin basic protein (MBP), with MMP-9 regulating initial Schwann cell-mediated MBP processing after L5 SNC. Acute and long-term therapy with GM6001 (broad-spectrum MMP inhibitor) protected from injury-induced MBP degradation, caspase-mediated apoptosis, macrophage infiltration in the spinal nerve and inhibited astrocyte activation in the spinal cord. The effect of GM6001 therapy on attenuation of mechanical allodynia was robust, immediate and sustained through the course of L5 SNC. In conclusion, MMPs mediate the initiation and maintenance of mechanical nociception through Schwann cell-mediated MBP processing and support of neuroinflammation.     

Attractin/mahogany protein expression in the rodent central nervous system

Attractin/Mahogany protein (Atrn) is known to be involved in a number of physiological and neuropathological events. Although the ubiquitous distribution of atrn mRNA has been described in neurons, lack of detailed information concerning the cellular and subcellular localization of protein product is impeding understanding of the role of Atrn. The present study immunohistochemically examined distributions of Atrn in rat and mouse central nervous systems (CNSs) by using a novel antibody for Atrn. Atrn was intensely expressed in most neurons and dendrites of large neurons, such as cortical pyramidal neurons and cerebellar Purkinje neurons. Intense Atrn expression was also observed in the neuropil of gray matter in many regions of the CNS, such as the main and accessory olfactory bulb, cerebral cortex, caudate putamen, dorsal lateral geniculate nucleus, medial eminence, superior colliculus, hippocampus, dentate gyrus, and layers 1 and 2 of the spinal cord. Furthermore, we found that astrocytes, microglia, and ependymal cells also express Atrn protein. Immunoelectron microscopy showed the subcellular distribution of Atrn in the plasma membrane of cell soma, dendrites, and spines in neurons and in the cytoplasmic membrane of Golgi apparatus, endoplasmic reticulum, and mitochondria in neurons and glial cells. These findings indicate that Atrn is more widely expressed throughout the CNS than previously reported, and expression of Atrn by various cell types suggests that Atrn may serve multiple functions in the CNS.     

Bone scanning--who needs it among patients with newly diagnosed prostate cancer?

BACKGROUND: We evaluated the relationship between serum PSA and clinical variables to eliminate bone scanning in patients with prostate cancer having a low probability of bone metastasis. METHODS: The study included 366 patients with newly diagnosed prostate cancer between 1999 and 2005. Bone metastasis was studied for its correlation with various clinical and pathological variables in these patients. RESULTS: Bone metastasis was found in 28 (7.7%) of 366 patients. Fourteen patients had skeletal symptoms related to bone metastasis. The risk for bone metastases increased considerably with increases of PSA level, clinical T stage and Gleason score. The metastasis was not found in 161 patients with serum PSA concentration of 10 ng/ml or lower. In 95 patients with the concentration between 10 and 20 ng/ml only two had the metastasis. These two patients had T2 disease and Gleason scores of 7 or greater. In 204 patients with clinical stage T1 disease, one (0.5%) had the metastasis. In 117 patients with Gleason scores of 6 or less, the metastasis was found in two (1.7%). CONCLUSIONS: For patients with serum PSA levels of 10 ng/ml or lower, bone scanning may be eliminated because of the negligible risk of bone metastases. In addition, scanning may not be necessary for those with PSA levels between 10 and 20 ng/ml, when they have T1 disease and Gleason scores of 6 or lower.     

Reversal of P-glycoprotein-mediated multidrug resistance by sipholane triterpenoids

Nineteen triterpenoids, possessing four different skeletons, have been reported so far from the Red Sea sponge Siphonochalina siphonella. However, no biological activity of these compounds was ever reported. This study describes the isolation of two new triterpenoids, siphonellinol C (3) and sipholenol I (4), along with several known sipholane triterpenoids from the Red Sea sponge Callyspongia (=Siphonochalina) siphonella. Allylic oxidation of the major sipholane triterpenoids, sipholenol A (1) and sipholenone A (2), by selenium dioxide afforded four C-28-oxidized derivatives. Sipholane triterpenoids along with their semisynthetic derivatives were evaluated for their cytotoxicity and effect on reversing P-glycoprotein-mediated MDR to colchicine. Sipholenol A was found to be the most potent, and it increased the sensitivity of resistant KB-C2 cells by 16 times toward colchicine. This is the first report related to reversal of cancer chemotherapy resistance using these triterpenoids.     

Role of Tyr306 in the C-terminal fragment of Clostridium perfringens enterotoxin for modulation of tight junction

We previously reported that the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a novel type of absorption enhancer that interacts with claudin-4 and that Tyr306 of C-CPE plays a role in ability of C-CPE to modulate barrier of tight junctions. In the current study, to investigate effects of Tyr306 on the C-CPE activity, we prepared some C-CPE mutants substituted Tyr306 with Trp (Y306W), Phe (Y306F) and Lys (Y306K). We found that Y306W and Y306F mutants of C-CPE had claudin-4 binding affinities and effects on the barrier function of tight junctions, whereas both of these properties were greatly reduced with the Y306K mutant. Finally, the Y306K but not the Y306F and Y306W mutants had reduced abilities to enhance absorption in rat jejunum. These results indicate that aromatic and hydrophobic properties, not hydrogen bonding potential, of Tyr306 are involved in the interaction of C-CPE with claudin-4 and in the modulation of the tight junction barrier function by C-CPE.     

Management and surgical resection for tracheobronchial tumors institutional experience with 12 patients

We reviewed the records of 12 patients with primary tracheobronchial tumors and various clinical characteristics treated at our institution to investigate our overall management experience with disease. Over a 21-year period, we treated 1405 cases of primary pulmonary neoplasms, of which 12 (0.9%) patients had primary tracheobronchial tumors with eight different histological types, including three adenoid cystic carcinomas, two bronchial carcinoids, two papillomas, one squamous cell carcinoma, one mucous gland adenoma, one inflammatory pseudotumor, one schwannoma, and one mucoepidermoid carcinoma. Eleven of the patients had symptoms of airway obstruction and/or secondary infection or bleeding. A complete resection was performed in ten, which included a sleeve lobectomy in seven, sleeve pneumonectomy in one, tracheal resection in one, and left main stem resection without lung resection in one. Median survival following complete resection was 91 months. When possible, a complete resection provides the best potential benefits and symptomatic relief for patients with tracheo-endobronchial tumors. Further, various options related to tracheobronchoplasty including conservative resection can be applied for surgical intervention.