ABSTRACT
INTRODUCTION: Positive peritoneal cytology (PPC) in endometrial cancer remains a controversial topic. Cleaved caspase-3 (CC3) and Ki-67 are excellent markers of apoptotic and proliferating cells, respectively. The objective of this study was to determine the significance of CC3 and Ki-67 expression in peritoneal cytology samples as prognostic factors for endometrial cancer with PPC. METHODS: Sixty endometrial cancer specimens with PPC alone were divided into 51 endometrioid tumours (43 endometrioid carcinomas and eight carcinomas with squamous differentiation) and nine non-endometrioid tumours (two serous carcinomas, three clear cell carcinomas and four carcinosarcomas). CC3 and Ki-67 expression in peritoneal cytology samples were immunocytochemically assessed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: Expression levels of CC3 and Ki-67 were not associated with any clinicopathological parameter. Patients with non-endometrioid tumours had significantly shorter DFS (P = .001) and OS (P = .001). Low CC3 expression (CC3Low ) was significantly associated with shorter OS (P = .02), but not DFS (P = .13). Multivariate analysis showed that non-endometrioid histology and CC3Low were independent prognostic factors. However, Ki-67 expression was not associated with survival. When endometrioid and non-endometrioid tumours were assessed separately, CC3Low was significantly associated with shorter DFS (P = .002) and OS (P = .002) in patients with non-endometrioid tumours. CONCLUSIONS: Our results suggest that CC3Low in peritoneal cytology samples is a poor prognostic factor in patients with endometrial cancers, especially non-endometrioid tumours. Immunocytochemical analysis of CC3 expression could potentially facilitate identification of patients with high-risk endometrial cancer with PPC.
Subject(s)
Caspase 3/metabolism , Endometrial Neoplasms/metabolism , Peritoneum/metabolism , Adenocarcinoma, Clear Cell/metabolism , Adenocarcinoma, Clear Cell/pathology , Apoptosis/physiology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Cell Proliferation/physiology , Disease-Free Survival , Endometrial Neoplasms/pathology , Female , Humans , Ki-67 Antigen/metabolism , Middle Aged , Peritoneum/pathology , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
This study showed that autoimmune arthritis induces especially severe osteoporosis in the periarticular region adjacent to inflamed joints, suggesting that arthritis increases the fragility fracture risk near inflamed joints, which is frequently observed in patients with RA. INTRODUCTION: Periarticular osteoporosis near inflamed joints is a hallmark of early rheumatoid arthritis (RA). Here we show that rheumatic inflammation deteriorates the bone quality and bone quantity of periarticular bone, thereby decreasing bone strength and toughness in a mouse model of RA. METHODS: Female BALB/c mice and SKG mice, a mutant mouse model of autoimmune arthritis on the BALB/c background, were used. At 12 weeks of age, BALB/c mice underwent either Sham surgery or bilateral ovariectomy (OVX), and SKG mice underwent intraperitoneal injection of mannan to induce arthritis. Eight weeks later, the mice were killed and the femurs and tibias were subjected to micro-computed tomography, Fourier transform infrared (FTIR) spectroscopic imaging, X-ray diffraction, histology, and mechanical testing. RESULTS: SKG mice developed significant trabecular bone loss in both the distal metaphysis of the femur and the lumbar vertebral body, but the extent of the bone loss was more severe in the distal metaphysis. Neither SKG nor OVX mice exhibited changes in the geometry and matrix properties of the diaphysis of the femur, whereas SKG mice, but not OVX mice, did exhibit changes in these properties in the distal metaphysis of the femur. Bone strength and fracture toughness of the distal metaphysis of the tibia adjacent to the inflamed ankle joint were significantly decreased in SKG mice. CONCLUSIONS: Autoimmune arthritis induces periarticular osteoporosis, characterized by deterioration of cortical bone geometry and quality as well as by trabecular bone loss, leading to severe bone fragility in periarticular bone adjacent to inflamed joints.
Subject(s)
Arthritis, Experimental/complications , Arthritis, Rheumatoid/complications , Osteoporosis/etiology , Animals , Arthritis, Experimental/diagnostic imaging , Arthritis, Experimental/physiopathology , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/physiopathology , Biomechanical Phenomena , Bone Density/physiology , Bone Resorption/diagnostic imaging , Bone Resorption/etiology , Bone Resorption/physiopathology , Female , Femur/diagnostic imaging , Femur/pathology , Femur/physiopathology , Mice, Inbred BALB C , Mice, Mutant Strains , Osteoporosis/diagnostic imaging , Osteoporosis/pathology , Osteoporosis/physiopathology , Ovariectomy , Severity of Illness Index , X-Ray MicrotomographyABSTRACT
This study showed that bisphosphonate was safe and effective for the treatment of bone disorders in stage 4 chronic kidney disease (CKD) rats. Intermittent teriparatide therapy showed an anabolic action on bone even under secondary hyperparathyroidism conditions without having an adverse effect on mineral metabolism in late-stage CKD. INTRODUCTION: Patients with late-stage CKD are at high risk for fragility fractures. However, there are no consensus on the efficacy and safety of osteoporosis medications for patients with late-stage CKD. In the present study, we aimed to examine the efficacy and safety of alendronate (ALN) and teriparatide (TPD) for treating bone disorder in late-stage CKD with pre-existing secondary hyperparathyroidism using a rat model of CKD. METHODS: Male 10-week-old Sprague-Dawley rats were subjected to a 5/6 nephrectomy or sham surgery and randomized into the following four groups: sham, vehicle (saline subcutaneous (sc) daily), ALN (50 µg/kg sc daily), and TPD (40 µg/kg sc daily). Medications commenced at 24 weeks of age and continued for 4 weeks. Micro-computed tomography, histological analysis, infrared spectroscopic imaging, and serum assays were performed. RESULTS: Nephrectomized rats developed hyperphosphatemia, secondary hyperparathyroidism (SHPT), and high creatinine, equivalent to CKD stage 4 in humans. ALN suppressed the bone turnover and increased the degree of mineralization in cortical bone, resulting in an improvement in the mechanical properties. TPD further increased the bone turnover and significantly increased the degree of mineralization, micro-geometry, and bone volume, resulting in a significant improvement in the mechanical properties. Both ALN and TPD had no adverse effect on renal function and mineral metabolism. CONCLUSIONS: BP is safe and effective for the treatment of bone disorders in stage 4 CKD rats. Intermittent TPD therapy showed an anabolic action on bone even under SHPT conditions without having an adverse effect on mineral metabolism in late-stage CKD.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Hyperparathyroidism, Secondary/complications , Hyperphosphatemia/complications , Osteoporosis/drug therapy , Renal Insufficiency, Chronic/complications , Alendronate/adverse effects , Alendronate/pharmacology , Alendronate/therapeutic use , Animals , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Femur/diagnostic imaging , Femur/drug effects , Femur/metabolism , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/drug effects , Male , Nephrectomy , Osteoporosis/diagnostic imaging , Osteoporosis/etiology , Rats, Sprague-Dawley , Teriparatide/pharmacology , X-Ray MicrotomographyABSTRACT
The first urine in the morning (total 15 samples) and whole day urine (total 4 days, 17 samples) were collected from a young healthy woman during the pregnancy and lactation period, to examine the possible interactions of urine components (methanol extracts) with P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs). The interaction was evaluated by measuring the intracellular accumulation of rhodamine123, a P-gp substrate, in LLC-GA5-COL150 cells, or calcein, an MRP substrate, in Caco-2 cells in the absence and presence of urine components. Four first urine samples out of 12 collected before childbirth and one sample out of three collected after childbirth suppressed P-gp function significantly. The effect of pregnancy and lactation on P-gp inhibitory potencies of urine components was not observed. The whole day urine samples showed a clear circadian rhythm, in which three first urine samples in the morning out of four showed greater P-gp inhibitory potencies than other daytime samples. Interaction of urine components with MRPs was not detected. In conclusion, the concentration of endogenous P-gp inhibitor(s) was higher in the first urine in the morning, showing a clear circadian rhythm. Normal pregnancy and lactation appeared not to significantly affect the P-gp inhibitory potencies of urine components.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/urine , Postpartum Period/urine , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , ATP-Binding Cassette Transporters/biosynthesis , Adult , Blotting, Western , Caco-2 Cells , Cell Line , Circadian Rhythm , Female , Fluoresceins/metabolism , Fluorescent Dyes , Humans , Lactation/physiology , Pregnancy , Rhodamine 123 , Young AdultABSTRACT
BACKGROUND: We evaluated the methylation patterns of histone H3 lysine 27 (H3K27), H3 lysine 36 (H3K36) and the expression of H3K27 methylase EZH2 in patients with colorectal carcinomas with metachronous liver metastasis to search for biomarkers identifying these patients. METHODS: Double 2-mm core tissue microarrays were made from 54 paraffin-embedded samples of primary colorectal adenocarcinomas and corresponding liver metastases and examined using an immunohistochemical analysis of dimethylation and trimethylation in H3K27, H3K36 and EZH2. Positive tumor cell staining for each histone modification (H-score) was used to classify patients into low- and high-staining groups, which were then examined to identify any correlations between the clinicopathological parameters and the clinical outcomes. RESULTS: The H-scores of H3K27me2 were lower in the liver metastases than in the corresponding primary tumors, while the H-scores of H3K36me2 were higher in the liver metastases than in the corresponding primary tumors (P < 0.001). H3K27me2 in the primary tumors correlated with tumor size (P = 0.016), H3K36me2 in the primary tumors correlated with histological type (P = 0.038), and H3K36me3 in the primary tumors correlated with lymph node metastasis (P = 0.017). In addition, lower levels of H3K27me2 in the primary tumors correlated with poorer survival rates (P = 0.039). The multivariate survival analysis showed that the H3K27me2 status is an independent prognostic factor for colorectal cancer patients (P = 0.047). CONCLUSIONS: Our findings suggest that the methylation level of H3K27me2 detected with immunohistochemistry may be an independent prognostic factor for metachronous liver metastasis of colorectal carcinomas.
Subject(s)
Adenocarcinoma/metabolism , Colorectal Neoplasms/metabolism , Histones/metabolism , Liver Neoplasms/metabolism , Neoplasms, Second Primary/metabolism , Polycomb Repressive Complex 2/metabolism , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Adenocarcinoma/secondary , Adult , Aged , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Methylation , Enhancer of Zeste Homolog 2 Protein , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Lysine , Male , Methylation , Middle Aged , Multivariate Analysis , Neoplasms, Second Primary/enzymology , Neoplasms, Second Primary/genetics , Neoplasms, Second Primary/secondary , Prognosis , Retrospective Studies , Risk Factors , Tissue Array AnalysisABSTRACT
BACKGROUND: Inhibitors of the epidermal growth factor (EGFR) signaling pathway have a major role in the treatment of KRAS wild-type colorectal cancer patients. The EGFR pathway has been shown to be activated in gastric cancer (GC). However, published data on KRAS and BRAF mutation status is limited in GC and has not been compared between GC from different geographic regions. METHODS: The prevalence of KRAS and BRAF mutations was established in 712 GC: 278 GC from the United Kingdom, 230 GC from Japan and 204 GC from Singapore. The relationship between KRAS/BRAF mutation status, DNA mismatch repair (MMR) status, clinicopathological variables and overall survival was analysed. RESULTS: Overall, 30 (4.2%) GC carried a KRAS mutation. In total, 5.8% of the UK GC, 4% of Japan GC and 1.5% of Singapore GC were KRAS mutant. KRAS mutant GC had fewer lymph node metastases in the UK cohort (P=0.005) and were more frequent in elderly patients in the Japan cohort (P=0.034). KRAS mutations were more frequent in MMR-deficient GC in the UK and the Japanese cohort (P<0.05). A BRAF mutation was only detected in a single Japanese GC. CONCLUSIONS: This large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of GC irrespective of country of origin, suggesting that this subgroup of GC may have developed along a common pathway. Further studies need to establish whether concomitant mutations or amplifications of other EGFR signalling pathway genes may contribute to the activation of this pathway in GC.
Subject(s)
DNA Mismatch Repair , DNA Repair-Deficiency Disorders , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , Stomach Neoplasms/genetics , ras Proteins/genetics , Aged , Cohort Studies , ErbB Receptors/genetics , Female , Genes, ras , Humans , Immunohistochemistry , Male , Middle Aged , Proto-Oncogene Proteins p21(ras) , Stomach Neoplasms/enzymologyABSTRACT
When a tumor invades the muscularis mucosa and submucosal layer (T1a-MM and T1b in Japan), esophageal squamous cell cancer poses 10-50% risk of lymph node metastasis. By this stage of esophageal cancer, surgery, although very invasive, is the standard radical therapy for the patients. Endoscopic mucosal resection (EMR) is the absolutely curable treatment for cancer in the superficial mucosal layer. Because of its minimal invasiveness, the indications of EMR may be expanded to include the treatment of T1a-MM and T1b esophageal carcinoma. To date, the clinical outcomes of EMR for T1a-MM and T1b patients have not been fully elucidated. Here, the retrospective analysis of the clinical outcomes is reported. Between January 1994 and December 2007, 247 patients underwent EMR at Kanagawa Cancer Center. Of these individuals, 44 patients with 44 lesions fulfilled the following criteria: (i) extended EMR treatment for clinical T1a-MM and T1b tumor; (ii) diagnosis of clinical N0M0; and (iii) follow up for at least 1 year, and negative vertical margin. These patients were reviewed for their clinical features and outcomes. Statistical analyses were performed by the Kaplan-Meier methods, the Chi-square test, and the Cox proportional hazard model. P-value of <0.05 was considered statistically significant. The data were analyzed in February 2009. Based on the informed consent and their general health conditions, 44 patients decided the following treatments immediately after the EMR: 2 underwent surgery, 1 underwent adjuvant chemotherapy, and 41 selected follow up without any additional therapy. Of the 41 patients, 20 selected this course by choice, 12 because of severe concurrent diseases, 2 because of poor performance status, and 7 because of other multiple primary cancers. Twelve patients died; two were cause specific (4.5%), eight from multiple primary cancers, one from severe concurrent diseases, and one from unknown causes. No critical complications were noted. Median follow-up time was 51 months (12-126). Five patients ultimately developed lymph node metastasis. One patient with adjuvant chemotherapy required surgery, and another was treated with chemotherapy whose subsequent death was cause specific. The other three patients received chemoradiotherapy and have not shown cause-specific death. Overall and cause-specific survival rates at 5 years were 67.3% and 91.8%, respectively. Among 41 patients treated by EMR alone, only one died from primary esophageal cancer (2.4%), and overall and cause-specific survival rates at 5 years were 75.6% and 97.6%, respectively. Multivariate analysis revealed that severe concurrent diseases including multiple primary cancers and the administration of 5-fluorouracil-based chemotherapy for multiple primary cancers significantly influenced survival (P= 0.025, hazard ratio [HR] 13.1 [95% confidence interval 1.5-114]) and (P= 0.037, HR 0.213 [95% confidence interval 0.05-0.914]), respectively. Eight and six patients developed metachronous esophageal squamous cell cancer and local recurrence, respectively. With the exception of one patient, they could be retreated endoscopically. EMR is a reasonable option for the patients with T1a-MM and T1b esophageal carcinoma without clinical metastasis, especially for the individuals with severe concurrent diseases. The prognostic factors for the benefit of EMR in such cases should be further examined.
Subject(s)
Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Mucous Membrane/surgery , Neoplasm Recurrence, Local/surgery , Neoplasms, Multiple Primary/drug therapy , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy, Adjuvant , Comorbidity , Esophageal Neoplasms/therapy , Esophagoscopy , Female , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Mucous Membrane/pathology , Neoplasm Invasiveness , Patient Preference , Retrospective Studies , Survival RateABSTRACT
AIM: To analyse the correlation between computed tomography (CT) findings of small lung adenocarcinomas and the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma. MATERIALS AND METHODS: A retrospective review of 300 lung adenocarcinoma lesions (size ≤20 mm) after surgical resection in 295 consecutive patients was performed. Tumours were defined as air-containing type if the ratio of the maximum dimension of the tumour on mediastinal windows to the maximum dimension of the tumour on lung windows was ≤50%, and as solid-density type if the ratio was >50%. The incidence between CT findings (air bronchogram, vascular involvement, pleural tags, notches, and spiculation) and pathological findings were investigated. RESULTS: Of the 142 air-containing lesions, 114 were adenocarcinoma in situ (AIS), 28 were minimally invasive adenocarcinoma (MIA), and none of the lesions were invasive adenocarcinoma. Of the 158 solid-density lesions, 30 were AIS, 24 were MIA, and 104 were invasive adenocarcinoma. Notches and pleural tags were commonly observed in cases of invasive adenocarcinoma (p < 0.05). CONCLUSIONS: In the air-containing type of small lung adenocarcinomas, AIS and MIA were observed but no cases of invasive adenocarcinoma were found. The presence of notches and pleural tags were a significant factor in invasive adenocarcinoma.
Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Adenocarcinoma/classification , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Air , Bronchography , Female , Humans , Lung Neoplasms/classification , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed , Tumor BurdenABSTRACT
BACKGROUND: To search for biomarkers identifying pancreatic cancer patients likely to benefit from adjuvant gemcitabine chemotherapy, we investigated the status of several histone modifications in pancreatic tumors and their relationship to clinicopathological features and outcomes. METHODS: Sixty one pancreatic cancer patients, primarily treated by surgical removal of tumors, were involved in the study. Thirty patients completed postoperative adjuvant gemcitabine, and in 31 it was discontinued. Tumor specimens were examined using immunohistochemistry for di- and tri-methylation of histone H3 lysine 4 (H3K4me2 and H3K4me3), dimethylation and acetylation of histone H3 lysine 9 (H3K9me2 and H3K9ac), and acetylation of histone H3 lysine 18 (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were examined for relationships to clinicopathological features and clinical outcomes. RESULTS: High expression of H3K4me3 was related to the well and moderately differentiated tumor histological type (p = 0.012) and low expression of H3K4me2 was related to the presence of perineural invasion (p = 0.007). No cellular histone modifications were associated with overall or disease-free survival of patients as a whole. In the subgroup analyses, a low level of H3K4me2 was significantly associated with worse disease free survival in patients that completed adjuvant gemcitabine (p = 0.0239). Univariate and multivariate hazard models also indicated that a low level of H3K4me2 was a significant independent predictor of disease-free survival (p = 0.007). CONCLUSION: H3K4me2 was found to be a predictor of response to adjuvant gemcitabine in Asian patients with pancreatic cancer.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Histones/metabolism , Pancreatic Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Deoxycytidine/therapeutic use , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lysine/metabolism , Male , Methylation , Middle Aged , Pancreatic Neoplasms/metabolism , GemcitabineABSTRACT
BACKGROUND: For spastic upper limb hemiparesis after stroke, we developed triple-element protocol of botulinum toxin type A (BoNTA) injection, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), and intensive occupational therapy (OT). Aim. To investigate the safety and feasibility of the protocol. Design. A preliminary study. Setting. At a university hospital. Population. Fourteen post-stroke patients with spastic upper limb hemiparesis (mean age: 54.9±9.2 years, time after onset: 87.1±48.2 months, ±SD). METHODS: In all patients, BoNTA was injected into spastic muscles of the affected upper limb (maximum total dose: 240 units). Four weeks later, they were hospitalized to receive 22 sessions of 20-min LF-rTMS and 120-min intensive OT daily over 15 days. Motor function of the affected upper limb was evaluated mainly using Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), motor activity log (MAL), and the severity of spasticity was measured with modified Ashworth scale (MAS) at BoNTA injection, discharge and four weeks post-discharge. RESULTS: All patients completed the protocol without any adverse effects. The FMA score and MAL scores, but not WMFT performance time, improved significantly at discharge. The MAS score of all examined muscles decreased significantly between BoNTA and discharge. The beneficial effect of the protocol on motor function and spasticity was almost maintained until four weeks after discharge. CONCLUSION: The protocol is safe and feasible, although further larger studies are needed to confirm its efficacy. CLINICAL REHABILITATION IMPACT: The protocol is a potentially useful neurorehabilitative approach for this patient population.
Subject(s)
Botulinum Toxins, Type A/therapeutic use , Muscle Spasticity/rehabilitation , Occupational Therapy/methods , Paresis/rehabilitation , Stroke/complications , Transcranial Magnetic Stimulation/methods , Adult , Aged , Aged, 80 and over , Botulinum Toxins, Type A/administration & dosage , Female , Follow-Up Studies , Humans , Injections, Intramuscular , Male , Middle Aged , Muscle Spasticity/etiology , Neuromuscular Agents/administration & dosage , Neuromuscular Agents/therapeutic use , Paresis/etiology , Retrospective Studies , Stroke Rehabilitation , Time Factors , Upper ExtremityABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare but fatal tumour. Although most MPM patients show pleural effusion at even the early stage, it is hard to diagnose as MPM at the early stage because a sensitive and reliable diagnostic marker for MPM has not been found in plasma or pleural effusion. METHODS: In this study, we investigated whether intelectin-1 was specifically contained in MPM cells and the pleural effusion of MPM patient by immunohistochemistry, western blotting, and enzyme-linked immunosorbent assay. RESULTS: Malignant pleural mesothelioma cell lines, but not lung adenocarcinoma cell lines, secreted intelectin-1. In immunohistochemistry, epithelioid-type MPMs, but neither pleura-invading lung adenocarcinomas nor reactive mesothelial cells near the lung adenocarcinomas, were stained with anti-intelectin antibodies. Pleural effusion of MPM patients contained a higher concentration of intelectin-1 than that of lung cancer patients. CONCLUSION: These results suggest that detection of intelectin-1 may be useful for a differential diagnosis of epithelioid-type MPM in immunohistochemistry and that a high concentration of intelectin-1 in pleural effusion can be used as a new marker for clinical diagnosis of MPM.
Subject(s)
Biomarkers, Tumor/metabolism , Cytokines/metabolism , Lectins/metabolism , Mesothelioma/metabolism , Pleural Effusion, Malignant/metabolism , Pleural Neoplasms/metabolism , Aged , Biomarkers, Tumor/analysis , Cell Line, Tumor , Cytokines/analysis , GPI-Linked Proteins , Humans , Lectins/analysis , Male , Middle Aged , Pleura/metabolism , Pleural Effusion, Malignant/chemistrySubject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/surgery , Light Coagulation/adverse effects , Retinal Detachment/diagnosis , Fluorescein Angiography , Fundus Oculi , Humans , Male , Middle Aged , Retinal Detachment/surgery , Tomography, Optical Coherence , Treatment Outcome , Vision Disorders/diagnosisABSTRACT
We conducted a feasibility study to examine whether small numbers of cancer cells could be utilised for analysis of the EGFR gene status using the loop-hybrid mobility shift assay, which is a modified heteroduplex technique. Cytology specimens obtained by transbronchial abrasion were successfully used for analysis of the EGFR gene status in 50 of 52 (96.2%) patients diagnosed with class V non-small-cell carcinoma. Furthermore, the relationship between the EGFR gene status and clinical outcome was analysed in 25 patients treated with gefitinib. Overall, 10 of 11 patients with EGFR mutations in exon 19 or 21 showed tumour regression with gefitinib treatment, compared to only two of 14 patients with wild-type EGFR. The response rate was significantly higher in the EGFR mutation group than in the wild-type EGFR group (90.9 vs 14.3%, P=0.00014). Logistic regression analysis revealed that EGFR mutations in cytology specimens represented an independent predictor of the gefitinib response. The overall and progression-free survivals were significantly longer in the EGFR mutation group than in the wild-type EGFR group (P<0.05). In conclusion, cytology specimens could be useful for analysing the EGFR status in the majority of patients with non-small-cell lung cancer to determine whether they are likely to benefit from gefitinib treatment.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Mutation/genetics , Quinazolines/therapeutic use , Adult , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Chi-Square Distribution , DNA Mutational Analysis/methods , ErbB Receptors/antagonists & inhibitors , Female , Gefitinib , Humans , Kaplan-Meier Estimate , Logistic Models , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Nucleic Acid Heteroduplexes/genetics , Treatment OutcomeABSTRACT
AIM: It has become obvious that the prognosis of bronchioloalveolar cell carcinoma (BAC) in small peripheral adenocarcinoma of the lung is good, but most cases actually treated as pulmonary adenocarcinoma in hospitals tend to be non-bronchioloalveolar cell carcinoma (non-BAC). The prognoses of non-BAC are greatly varied. We studied the relationships between the morphometrical features and the prognoses of non-BAC. METHODS: In total, 69 cases of non-BAC measuring Subject(s)
Adenocarcinoma/pathology
, Bronchial Neoplasms/pathology
, Neoplasm Recurrence, Local/pathology
, Adenocarcinoma/mortality
, Adenocarcinoma, Bronchiolo-Alveolar/pathology
, Aged
, Bronchial Neoplasms/mortality
, Disease-Free Survival
, Female
, Follow-Up Studies
, Humans
, Male
, Middle Aged
, Neoplasm Recurrence, Local/mortality
, Neoplasm Staging
, Prognosis
, Proportional Hazards Models
, Survival Rate
ABSTRACT
Pilomatrix carcinoma, a rare malignant soft tissue tumour, is the malignant variant of pilomatricoma. We report a case of pilomatrix carcinoma of the axilla. CT demonstrated a well-circumscribed, sand-like calcified mass. MRI showed diffusely inhomogeneous, mixed signal intensities with inhomogeneous enhancements. The MRI findings were different from those previously reported for pilomatricoma.
Subject(s)
Axilla , Calcinosis/diagnosis , Hair Diseases/diagnosis , Pilomatrixoma/diagnosis , Skin Neoplasms/diagnosis , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Tomography, X-Ray Computed/methodsABSTRACT
A 43-year-old-woman who had sever anterior chest pain visited our hospital on April 3, 2000. A well-defined abnormal shadow was seen in the middle and lower field of the right lung on chest X-ray. Computed tomography showed a large fat density mass in the right pleural cavity with a septum enhanced by contrast medium. Percutaneous needle biopsy revealed lipoma or liposarcoma. Complete resection could be done with combined resection of right lung, lpericardium, parietal pleura and diaphragm. Final histologic diagnosis was well differentiated liposarcoma. There are few reports of liposarcoma arising in the thoracic cavity, we present our case and review the 23 cases reported from the Japanese literatures.
Subject(s)
Liposarcoma/surgery , Pleural Cavity , Thoracic Neoplasms/surgery , Adult , Female , Humans , Thoracic Surgical Procedures/methodsABSTRACT
New polyhydroxylated alkaloids, (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxypyrrolidine-N-propionamide from the root bark of Morus alba L., and 4-O-alpha-D-galactopyranosyl-calystegine B(2) and 3 beta,6 beta-dihydroxynortropane from the fruits, were isolated by column chromatography using a variety of ion-exchange resins. Fifteen other polyhydroxylated alkaloids were also isolated. 1-Deoxynojirimycin, a potent alpha-glucosidase inhibitor, was concentrated 2.7-fold by silkworms feeding on mulberry leaves. Some alkaloids contained in mulberry leaves were potent inhibitors of mammalian digestive glycosidases but not inhibitors of silkworm midgut glycosidases, suggesting that the silkworm has enzymes specially adapted to enable it to feed on mulberry leaves. The possibility of preventing the onset of diabetes and obesity using natural dietary supplements containing 1-deoxynojirimycin and other alpha-glucosidase inhibitors in high concentration is of great potential interest.
Subject(s)
Alkaloids/isolation & purification , Bombyx/chemistry , Glycoside Hydrolases/antagonists & inhibitors , Plant Leaves/chemistry , Animals , Bombyx/enzymology , Chromatography, Ion Exchange , Diabetes Mellitus/drug therapy , Glycoside Hydrolases/metabolism , Humans , Hydroxylation , Phytotherapy , Plant Leaves/metabolism , Plants, Medicinal/therapeutic useABSTRACT
In March 1982, a 60-old woman presented with an International Federation of Gynecology and Obstetrics grade 1, stage Ib endometrial adenoacanthoma, histological subtype of endometrial carcinoma. The patient underwent radical hysterectomy and was followed up for 10 years, without disease. In August 1998, an abnormal shadow in the right lung was suggested on a chest X-ray film at her routine health check-up and she came to our hospital for further evaluation. A thin-section computed tomographic scan of the chest suggested a malignant lung tumor, but the diagnosis remained tentative. Open biopsy was recommended, but the patient refused and was followed up on an outpatient basis. In November 1999, a thin-section computed tomographic scan of the chest revealed a slightly enlarged tumor and laboratory examination showed a high serum progastrin-releasing peptide concentration of 90.7 pg/ml. We performed partial resection of right upper lobe with video-assisted thoracic surgery. Pathological examination confirmed the lung tumor had metastasized from endometrial adenoacanthoma. Immunohistochemical stainings of estrogen receptor and progesterone receptor were positive both in the primary and lung tumor, only in the component of adenocarcinoma. After surgery, the serum progastrin-releasing peptide concentration remained unchanged. The patient is currently alive and free of disease.
Subject(s)
Adenocarcinoma/secondary , Endometrial Neoplasms/pathology , Lung Neoplasms/secondary , Adenocarcinoma/surgery , Aged , Endometrial Neoplasms/surgery , Female , Humans , Hysterectomy , Lung Neoplasms/surgery , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Thoracic Surgery, Video-AssistedABSTRACT
Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including cancer development, progression and metastasis. Its expression is induced by a variety of stimuli such as TNF-alpha and Ras proto-oncogene. However, differential OPN expression and its regulation in each histologic type of lung cancer are not well established. In this study, we assessed expression of OPN in lung cancer tissues with immunohistochemical analysis. OPN was predominantly expressed in tumor cells of non-small cell lung cancer (NSCLC) tissues: 11 of 16 cases (68.8%) of squamous cell carcinoma (SCC), five of 24 cases (20.8%) of adenocarcinoma (AD), but only two of 18 cases (11%) of small cell lung cancer (SCLC). Expectedly, OPN was principally expressed in NSCLC cell lines (H322 cells and HL460 cells) but not in SCLC cell line (H69 cells) by Western blotting and Northern blotting. Interestingly, Ras-p21 was specifically co-expressed with OPN staining in eight of eight cases with SCC (100%), whereas it was demonstrated in three of ten cases (30%) with AD and only one of 18 cases (5%) with SCLC. Collectively, these results suggest that OPN is mainly expressed in NSCLC, especially among SCC. OPN expression may be tightly regulated by Ras oncogene, and its concomitant induction with Ras activation may play a crucial role in the development of SCC.
Subject(s)
Lung Neoplasms/metabolism , Sialoglycoproteins/biosynthesis , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Carcinoma, Small Cell/genetics , Carcinoma, Small Cell/metabolism , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Female , Gene Expression Regulation, Neoplastic , Genes, ras/genetics , Humans , Immunohistochemistry , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Osteopontin , Proto-Oncogene Mas , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Sialoglycoproteins/genetics , Tumor Cells, CulturedABSTRACT
In a patient with chronic hemodialysis, the high risk of calcific degeneration of biological prosthetic valve and anticoagulant related complications after valve replacement have been reported. A 71-year-old woman with hemodialysis underwent the edge to edge repair combined with ring-annuloplasty for mitral regurgitation caused by the anterior leaflet prolapse without any torn chordae. Postoperative course was uneventful. There was no significant mitral regurgitation. Double mitral orifices were confirmed by the postoperative echocardiography. A calculated functional mitral valve area was 3.06 cm2. The edge to edge repair is a simplified technique and carried out in a short time. We believe the edge to edge repair is a useful technique for anterior mitral valve prolapse in a patient with chronic hemodialysis.