Relationship between immune checkpoint proteins and neoadjuvant chemotherapy response in breast cancer.

INTRODUCTION: Following major developments in cancer immunotherapy, treatments targeting immune checkpoint proteins (ICP) gained interest in breast cancer, though studies mostly focus on patients with metastatic disease as well as patients nonresponsive to the conventional treatments. Herein, we aimed to investigate the levels of ICP in tumor stroma and tumor infiltrating lymphocytes, and tumor tissue prior to neoadjuvant chemotherapy administration to evaluate the relationship between ICP levels, clinicopathological parameters, and NAC response. MATERIALS AND METHODS: This study was conducted with 51 patients where PD-1, PD-L1, CTLA-4, TIM-3, CD24 and CD44 levels were investigated in CD45+ cells while CD326, CD24, CD44 and PD-L1 protein expression levels were investigated in CD45- population. In addition, CD44 and CD24 levels were evaluated in the tumor stroma. TIL levels were investigated according to the TILS Working Group. Treatment responses after NAC were evaluated according to the MD Anderson RCB score. RESULTS: Our results revealed positive correlation between CTLA-4 and CD44 expression in cases with high TIL levels as well as TIL levels and CTLA-4 expression in cases with partial response. Similarly, positive correlation was detected between TIM3 and PD-L1 levels in cases with good response. In addition, a negative correlation between TILs after NAC and PD-1/PD-L1 expression in lymphocytes in cases with partial complete response. CONCLUSIONS: Our study provides preliminary data about the correlation between ICP and clinicopathological status and NAC response in breast cancer, in addition to underlining the requirement for further research to determine their potential as therapeutic targets.

Effects of tamoxifen therapy on sciatic nerve crush injury: An experimental study in rats.

OBJECTIVE: This study aimed to determine the effects of tamoxifen on sciatic nerve crush injury in a rat model using histopathological, histomorphometric, and immunohistochemical approaches. METHODS: In this study, 24 male Sprague-Dawley rats aged of 5 to 7 weeks and weighing between 300 g and 400 g were used. The rats were randomly divided into 3 groups: control (group C), sciatic nerve injury (group SNI), and sciatic nerve injury with tamoxifen (group SNT). The sciatic nerve crush injury model was performed using the De Koning's crush force method. In group C, only a skin incision was made and then the skin was sutured. In group SNI, the injury model was performed but no treatment was applied. In group SNT, the injury model was executed, and then 40 mg/kg/day tamoxifen was given for 4 weeks by intraperitoneal methods. At the end of 4 weeks, all animals were killed using high doses of an anesthetic. Approximately, 2-cm sciatic nerve samples were obtained for histopathological, histomorphometric, and immunohistochemical analyses using the old skin incision. RESULTS: In the histopathological examination, vascular congestion and density of vacuolization were significantly lower in group SNT than in group SNI (p<0.05). In the histomorphometric examination, the mean sciatic nerve diameter was 306±62 µm in group C, 510±42 µm in group SNI, and 204±23 µm in group SNT. A significant difference was observed in the sciatic nerve diameter measurements among the 3 groups (p<0.05). In pairwise comparisons, the mean sciatic nerve diameter was significantly lower in group SNT than in group SNI (p=0.00002). Sciatic nerve diameter measurements of both groups were found to be significantly higher than group C (p<0.05). The mean epineurium thickness was 17±0.8 µm in group C, 32±2.5 µm in group SNI, and 17±0.8 µm in group SNT. A significant difference was observed in the epineurium thickness measurements among the 3 groups (p<0.05). In pairwise comparisons, the epineurium thickness was significantly higher in group SNI than in groups SNT and C (p<0.05). In the immunohistochemical analysis, S100 immunoreactivity was found significantly higher in group SNI than in the other 2 groups (p<0.05). CONCLUSION: The histomorphometric, histopathological, and immunohistochemical data obtained from this study have shown that tamoxifen has a beneficial effect on sciatic nerve crush injury in the experimental rat model.

Polypropylene composite hernia mesh with anti-adhesion layer composed of polycaprolactone and oxidized regenerated cellulose.

Hernia surgeries are at the top of the general surgery operations. However, visceral adhesion, which is one of the worst complications of these operations, is still a major problem. One of the most preferred methods to prevent adhesion is the use of biomaterials. Polypropylene (PP) mesh is frequently preferred product in clinical applications owing to its mechanically robust structure against deformation within the body. However, PP meshes do not have anti-adhesive properties. Oxidized regenerated cellulose (ORC), on the other hand, is one of the most preferred products in preventing the adhesion in clinical use. ORC is not easily processable due to solubility limitations; and it must be used externally. In this study, for the first time, we designed a composite mesh structure with ORC and produced an antibacterial and anti-adhesive double-sided mesh by electro-spinning ORC micro-particles with poly(ε­caprolactone) (PCL) on PP mesh to form a composite structure. We conducted in vitro cell culture studies to determine bio-compatibility performances. We evaluated the anti-adhesion and comprehensive bio-compatibility studies through in vivo experiments. The results revealed that ORC presence and optimization of ORC degradation by coating with PCL play an important role in adhesion prevention and introduced a product prototype with efficient anti-adhesion properties.

A Polypropylene-Integrated Bilayer Composite Mesh with Bactericidal and Antiadhesive Efficiency for Hernia Operations.

Polypropylene (PP) mesh has been widely used in hernia fixation operations for more than one hundred years, and peritoneal adhesion is still one of the main complications after hernia fixation operations. For preventing peritoneal adhesion, many solutions have been offered, including gel systems, adhesion barrier membranes, and bilayer meshes. Among these, bilayer meshes come to the forefront as they serve for both hernia repair and adhesion prevention. In this study, we developed an easy and effective method to produce a multifunctional PP-integrated bilayer mesh composed of poly(lactic-co-glycolic acid) and chitosan with no need for neutralization. We made the composite mesh by electrospinning a layer onto the PP mesh. We evaluated the material characteristics, in vitro bactericidal activities, and interactions between the cells and materials. Then, we conducted in vivo efficiency studies. The results proved that the PP-integrated bilayer composite mesh is bactericidal against Escherichia coli and Staphylococcus aureus, is tissue-compatible, and supremely prevents adhesion.

Correction: Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats.

[This corrects the article DOI: 10.1371/journal.pone.0156495.].

Retinal Electrophysiological Effects of Intravitreal Bone Marrow Derived Mesenchymal Stem Cells in Streptozotocin Induced Diabetic Rats.

Diabetic retinopathy is the most common cause of legal blindness in developed countries at middle age adults. In this study diabetes was induced by streptozotocin (STZ) in male Wistar albino rats. After 3 months of diabetes, rights eye were injected intravitreally with green fluorescein protein (GFP) labelled bone marrow derived stem cells (BMSC) and left eyes with balanced salt solution (Sham). Animals were grouped as Baseline (n = 51), Diabetic (n = 45), Diabetic+BMSC (n = 45 eyes), Diabetic+Sham (n = 45 eyes), Healthy+BMSC (n = 6 eyes), Healthy+Sham (n = 6 eyes). Immunohistology analysis showed an increased retinal gliosis in the Diabetic group, compared to Baseline group, which was assessed with GFAP and vimentin expression. In the immunofluorescence analysis BMSC were observed to integrate mostly into the inner retina and expressing GFP. Diabetic group had prominently lower oscillatory potential wave amplitudes than the Baseline group. Three weeks after intravitreal injection Diabetic+BMSC group had significantly better amplitudes than the Diabetic+Sham group. Taken together intravitreal BMSC were thought to improve visual function.

Brown tumor as an unusual but preventable cause of spinal cord compression: Case report and review of the literature.

Brown tumor (BT), also known as osteoclastoma, may appear in the context of primary and secondary hyperparathyroidism. Spinal cord compression due to the BT is extremely rare. We present here an unusual case of BT involving thoracal spine and mandible. A 26-year-old woman, who had been on hemodialysis for chronic renal failure for over 6 years, got admitted with dorsal pain and progressive weakness in her lower extremities and gait disturbances. Neurological examination revealed spastic paraparesis and symmetrically hyperactive tendon reflex in the lower extremities. She had hypoesthesia under T10 level. On physical examination, a swelling on the left side of her jaw was also detected. Magnetic resonance imaging (MRI) showed cord compression due to an extradural mass lesion at T8 level. A computerized tomography (CT) scan showed that this expansile lytic lesion was caused by the collapse of vertebra corpus (T8) at that level. CT of the mandible revealed an expansile lytic lesion on left arm of the mandible. Laboratory findings were nearly normal except parathormone level elevation to 1289 pg/mL (normal 30-70 pg/mL). Ultrasound examination showed enlargement of the parathyroid glands. The patient underwent an emergency decompression and stabilization surgery. The lesion was fragile and reddish in appearance and was easy to aspirate. The tumor was reported as "BT." Her weakness in the lower extremities improved in the early postoperative period. Following surgical intervention, the patient was transferred to nephrology clinic for additional medical treatment.

The effects of resveratrol on tendon healing of diabetic rats.

OBJECTIVE: The aim of this study was to determine the effects of resveratrol on the tendon healing process of streptozotocin-induced diabetic rats. METHODS: The study included 16 male Sprague-Dawley rats. Streptozotocin was administered to induce diabetes and bilateral tenorrhaphy of the Achilles tendons was performed. Intraperitoneal resveratrol was injected in the experimental group (n=8) and saline in the control group (n=8) during the postoperative period. Rats were sacrificed at the 14th day. Right side tendons were evaluated biomechanically and left side tendons histologically. RESULTS: Difference in mean tendon tensile strength was not statistically significant between groups (p>0.05). Histologic evaluations of the repair zones showed greater configuration of the newly synthesized collagen in the experimental group. The ratio of the newly synthesized collagen area to the healing region area was significantly higher in the experimental group then the control group (p<0.01). CONCLUSION: Resveratrol appears to have a positive impact on the process of tendon healing in diabetic conditions in the first 14 days.

Gorham disease of the craniocervical junction: X-ray, computed tomography, and magnetic resonance imaging findings.

BACKGROUND CONTEXT: Gorham disease of massive osteolysis is a spontaneous, idiopathic, and progressive form of primary osteolysis. It has no age, sex, or race predilection, and patients are mostly asymptomatic until severe deformity or pathological fracture becomes evident. PURPOSE: A patient with craniocervical involvement is presented, describing imaging findings with a review of the literature to provide an insight into the disorder. STUDY DESIGN/SETTING: Case report and review of the literature. METHODS: X-ray, computed tomography, and magnetic resonance imaging findings of a patient with findings related to the site of involvement. RESULTS: All images demonstrate osteolysis typically described for the disease. Differential diagnosis and key features are indicated. Operative findings and pathological analysis were also consistent with the findings. Patient's follow-up is also reported. CONCLUSIONS: This benign appearing yet disabling disease may become fatal in relation to the site involved. Acknowledging imaging findings may provide early diagnosis for timely intervention or supportive management.

Solid pseudopapillary tumor of the pancreas: a case series of 9 patients.

BACKGROUND/AIMS: Solid pseudopapillary tumor is a rare exocrine tumor of the pancreas. There is no clear consensus on its etiology, origin and treatment. In this study, the clinical, pathological and immunohistochemical features of nine patients with solid pseudopapillary tumor were re-evaluated in view of the current literature findings. MATERIALS AND METHODS: We studied nine cases diagnosed with solid pseudopapillary tumor between 2005 and 2010. The clinical, pathological and laboratory data were analyzed. RESULTS: On microscopy, all tumors had well-defined borders and were separated from surrounding pancreatic tissue by a thick fibrous capsule. The tumor consisted mainly of pseudopapillary structures with focal solid areas accompanied by wide hemorrhagic and cystic regions. The typical morphological features were present to varying degrees. Of the nine cases, one relapsed approximately two years after the diagnosis, and our laboratory also evaluated the surgical specimen of local recurrence. CONCLUSIONS: While some new light has been shed on the clinicopathological features of solid pseudopapillary tumor concerning its etiology, origin and treatment methods, there is much to be understood. Further studies focusing on genetics, pathogenesis and prognosis are needed for a better understanding of this entity.

Chondromyxoid fibroma of frontal bone: a case report and review of the literature.

Chondromyxoid fibroma is an unusual benign tumor of cartilaginous tissues that may be confused with other some malign tumors. It is rarely seen in the skull. A 45-year-old female was admitted with painless bony swelling in the forehead. Computerized tomography demonstrated a well-defined expansive lesion with a sclerotic margin measuring approximately 3 cm in diameter in the right frontal bone. On MRI, T1-weighted images revealed a well circumscribed, lobulated and strongly enhancing lesion. On the T2-weighted images, the lesion showed high heterogeneous signal intensity. The patient underwent tumor excision with craniectomy, then acrylic cranioplasty. The histopathological diagnosis was chondromyxoid fibroma. There was no recurrence in a period of 22-months. In conclusion, chondromyxoid fibroma is a benign primary bone tumor that is located extremely rarely in the frontal bone. Accurate initial diagnosis of such tumors are important for appropriate treatment. En block surgical resection of the tumor is the cornerstone of treatment.

Lipedematous scalp and lipedematous alopecia: report of three cases in white adults.

Lipedematous scalp (LS) and lipedematous alopecia (LA) are rare conditions of unknown etiology characterized by a thick and boggy scalp due to increase in the subcutaneous fat layer. Besides the changes in the texture of skin, varying degrees of hair loss are seen in patients with LA. In this report, we present two cases with LA and one case with LS in white adults. On examination, a boggy and soft swelling of the scalp was detected in all patients. In addition, the patients with LA had alopecic areas over the boggy scalp. Histopathologic examinations of skin biopsy specimens and magnetic resonance imaging of the scalp showed increased thickness of subcutaneous fat tissue in all patients. The exact etiopathogenesis of LA and LS remain unknown. These conditions may be either reactive or compansatory responses versus yet undetected stimuli, or represent a genetic tendency. Both of the these entities have been initially reported mostly in adult black females, however, we believe that LA and LS may well occur in white subjects and may be more widespread and frequently observed than previously supposed.