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1.
Int J Surg Case Rep ; 108: 108379, 2023 Jul.
Article En | MEDLINE | ID: mdl-37302174

INTRODUCTION AND IMPORTANCE: Patellar bone tumors are very rare, and most are benign or of intermediate type. In this report, we describe our experience of a metastatic patellar bone tumor caused by gastric cancer, which resembled a very rare primary or secondary aneurysmal bone cyst and review the literature. CASE PRESENTATION: A 65-year-old man presented with severe pain in the patellar region and marked limitation of the knee joint range of motion. He had a history of gastric cancer; however, epidemiological, clinical, and imaging findings led us to strongly suspect an aneurysm-like bone cyst. Thus, we performed bone tumor curettage and autologous artificial bone grafting without biopsy because of the severe pain. Pathology results showed gastric cancer metastasis; hence, patellectomy and patellar tendon augmentation with femoral fascia were performed. The Musculoskeletal Tumor Society (MSTS) score was taken postoperatively to assess pain and function. CLINICAL DISCUSSION: We experienced a very rare gastric cancer-related metastatic patellar bone tumor, which resembled a primary or secondary aneurysmal bone cyst in frequency and imaging findings. Patellectomy was ultimately performed, and the patient's MSTS score improved markedly. CONCLUSION: Despite its very low frequency, patellar metastatic bone tumors must be taken into account without being misled by the frequency or imaging findings and a biopsy should necessarily be performed.

2.
Int J Surg Case Rep ; 95: 107189, 2022 Jun.
Article En | MEDLINE | ID: mdl-35598340

INTRODUCTION AND IMPORTANCE: Scapular prostheses are useful in shoulder stability after shoulder girdle resection for malignant bone tumors; however, they are difficult to obtain in Japan. Therefore, other methods must be considered, depending on the extent of resection. We report a case in which a clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis were used to ensure shoulder stability and preserve stable upper limb function. CASE PRESENTATION: A 56-year-old man presented with a large mass and edema over the entire right scapula, which caused severe pain, limited the shoulder's range of motion, and impaired function of the entire upper extremity. Clinical imaging and pathological findings indicated a diagnosis of conventional chondrosarcoma. Using the Malawer technique type IVB, we resected the shoulder girdle and secured shoulder stability with a clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis. To evaluate the patient, we obtained his Musculoskeletal Tumor Society (MSTS) and Disabilities of Arm, Shoulder, and Hand (DASH) scores 3 months postoperatively. CLINICAL DISCUSSION: To preserve the function of the patient's elbow and hand, the stability of his shoulder was important. We could achieve this stability by using a prosthesis available in Japan. The patient's MSTT and DASH scores improved remarkably. CONCLUSION: A clavicle-locking plate, Nesplon tape, and a proximal humeral prosthesis can be used to ensure shoulder stability after scapular girdle resection and can preserve or improve upper limb function.

4.
Dig Dis Sci ; 63(6): 1605-1612, 2018 Jun.
Article En | MEDLINE | ID: mdl-29564670

BACKGROUND: According to the Japanese Esophageal Society (JES) guidelines, risk factors for lymph node (LN) metastasis in the muscularis mucosa (MM)/submucosa to a depth of up to 200 µm (SM1) in cases of esophageal squamous cell carcinomas (ESCCs) include the presence of lymphatic invasion (ly), venous invasion (v), infiltration pattern (INF)c, and SM1. The long-term prognoses of these patients are unclear, and there are very few reports on the validation of the curative criteria for MM/SM1 ESCCs. AIMS: To examine the long-term prognoses of these patients and the risk factors for LN metastasis of MM/SM1 ESCCs after endoscopic resection (ER). METHODS: This study included patients with MM/SM1 ESCCs who underwent ER at Hiroshima University Hospital from December 1990 to November 2016. We evaluated the clinicopathological characteristics of 98 patients and overall survival, disease-specific survival, recurrence-free survival, and recurrence rates in the e-curative and non-e-curative groups. RESULTS: The mean observation period was 75 months. There was no significant difference in disease-specific survival rate between the e-curative and non-e-curative groups (100 vs. 98%). There was no significant difference in disease-specific survival rates between the groups (100 vs. 98%). In contrast, the LN recurrence-free survival rate in patients with INFa, ly(-), and v(-) was significantly higher than that in patients with INFb/c, ly(+), or v(+) (100 and 87%, P < 0.05). CONCLUSION: Contrary to the JES guidelines, our findings suggest that new criteria (MM/SM1, INFa, negative vertical margin (VM0), ly[-], and v[-]) may be associated with curative ER without additional treatment.


Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagoscopy , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Disease Progression , Disease-Free Survival , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Esophagectomy/adverse effects , Esophagectomy/mortality , Esophagoscopy/adverse effects , Esophagoscopy/mortality , Female , Hospitals, University , Humans , Japan , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
5.
Dis Esophagus ; 31(7)2018 Jul 01.
Article En | MEDLINE | ID: mdl-29267962

Endoscopic submucosal dissection (ESD) is a widely accepted procedure for superficial esophageal squamous cell carcinoma (SESCC) limited to the epithelium or lamina propria mucosae (EP/LPM). We aimed to compare the efficacy of endoscopic ultrasonography (EUS) and magnifying endoscopy with narrow band imaging (ME-NBI) for predicting the tumor invasion depth in patients with SESCC. Specifically, we evaluated the ability of these examinations to distinguish EP/LPM from SESCC invading the muscularis mucosae or superficial submucosa (MM/SM1) and more deeply invasive lesions before ESD.We retrospectively analyzed a database of all patients with SESCC who had undergone both EUS and ME-NBI for pretreatment staging and ESD resection at Hiroshima University Hospital between September 2007 and June 2015. The clinicopathologic characteristics of SESCCs were classified according to the Japanese Classification of Esophageal Cancer.A total of 174 lesions in 174 patients were included: 124 (71%) EP/LPMs, 35 (20%) MM/SM1s, and 15 (9%) SESCCs invading the mid submucosae (SM2). The sensitivity of EUS and of ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 72% and 83%, respectively. The accuracy of EUS and ME-NBI in distinguishing EP/LPM from MM/SM1 and more invasive lesions was 70% and 82%, respectively. Sensitivity and accuracy of ME-NBI in distinguishing EP/LPM from MM/SM1 and more deeply invasive SESCCs is significantly higher than those of EUS (P = 0.048 and P = 0.017, respectively).ME-NBI may be more useful than EUS for the determination of SESCC invasion depth before ESD.


Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Endosonography , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Esophagoscopy , Narrow Band Imaging , Aged , Carcinoma, Squamous Cell/surgery , Endoscopic Mucosal Resection , Endosonography/methods , Esophageal Mucosa/diagnostic imaging , Esophageal Mucosa/pathology , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma , Esophagoscopy/methods , Female , Humans , Male , Middle Aged , Narrow Band Imaging/methods , Neoplasm Invasiveness/diagnostic imaging , Preoperative Period , Retrospective Studies , Sensitivity and Specificity
6.
Transplant Proc ; 49(7): 1634-1638, 2017 Sep.
Article En | MEDLINE | ID: mdl-28838454

BACKGROUND: We report a case of acute rejection of a liver graft, together with the occurrence of de novo donor-specific antibodies (DSAs), in a 53-year-old Japanese man who had undergone deceased-donor liver transplantation. METHODS: The graft rejection was triggered by low cyclosporine levels and pegylated interferon treatment for the recurrence of hepatitis C virus (HCV) infection 18 months after transplantation. Although the graft was ABO-compatible, pre-formed DSA B51 was detected; therefore, total plasma exchange was performed and intravenous rituximab (500 mg/body) was administered before transplantation. RESULTS: DSA was absent 6 months after transplantation. HCV recurrence was treated with pegylated interferon-α-2a. Renal function deteriorated with this anti-HCV therapy, with serum cyclosporine levels decreasing to 50 ng/mL. A rapid virologic response was achieved, but liver function deteriorated after 3 months of anti-HCV therapy, with histologic evidence of acute cellular rejection and formation of de novo DSAs. Anti-thymocyte globulin was administered for 5 days, which led to immediate improvement in liver function. However, renal function declined, warranting hemodialysis. The patient recovered 2 months after acute rejection, although de novo DSAs persisted. CONCLUSIONS: Careful immunologic monitoring may be required for patients receiving interferon therapy for HCV infection to maintain sufficient blood levels of immunosuppressive agents and to prevent acute liver graft rejection.


Antiviral Agents/adverse effects , Cyclosporins/blood , Graft Rejection/chemically induced , Interferon-alpha/adverse effects , Liver Transplantation/adverse effects , Polyethylene Glycols/adverse effects , Antibodies/immunology , Antibody Specificity , Antilymphocyte Serum/therapeutic use , Graft Rejection/blood , Graft Rejection/immunology , Hepacivirus/immunology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Immunosuppressive Agents/blood , Male , Middle Aged , Monitoring, Immunologic , Plasmapheresis , Postoperative Complications/drug therapy , Postoperative Complications/virology , Recombinant Proteins/adverse effects , Recurrence , Tissue Donors
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2015: 4387-90, 2015 Aug.
Article En | MEDLINE | ID: mdl-26737267

Measurements of dielectric constants and conductivities of invasive ductal carcinoma (IDC) tissues such as scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma were made by use of microwave dielectric spectroscopy. Dielectric constants of inhomogeneous breast tumor tissues were analyzed by use of Bruggeman's effective medium approximation theory. It is found that the dielectric constants of scirrhous carcinoma, solidtubular carcinoma and papillotubular carcinoma of IDC tissues have correlation to the volume fractions of the cancer cells in the stroma tissues.


Breast Neoplasms , Humans
8.
Case Rep Gastroenterol ; 7(3): 492-7, 2013 Sep.
Article En | MEDLINE | ID: mdl-24474898

We report a rare case of metastasis of hepatocellular carcinoma (HCC) to the small bowel that presented as a pedunculated epithelial polyp. A 60-year-old man with liver cirrhosis type B was treated for HCC (stage IVb) at our hospital. He had been admitted for melena and anemia. Capsule endoscopy was performed in this patient with obscure gastrointestinal bleeding. It showed a polypoid lesion with bleeding in the ileum. Double-balloon endoscopy was performed. The lesion was determined to be a pedunculated polyp in the ileum. Histological examination of biopsy specimens showed tumor cells resembling HCC. We performed endoscopic mucosal resection for the lesion by double-balloon endoscopy to prevent bleeding from the tumor. The patient had no melena or anemia and his condition improved after endoscopic mucosal resection. However, he died of liver failure 2 months later.

9.
Pathobiology ; 77(5): 273-7, 2010.
Article En | MEDLINE | ID: mdl-21116119

The characteristics of synchronous and subsequent lesions of serrated adenomas (SAs) of the colorectum are still unclear. This study aimed to clarify the characteristics of synchronous and subsequent lesions of SAs compared with tubular adenomas (TAs) of the colorectum. Patients were divided into 2 groups: SA (127 patients) and TA (158 patients). The mean follow-up durations in the SA and TA groups were 39.7 and 42.7 months, respectively. The number and clinical features of the synchronous and subsequent lesions of both groups were examined. In the SA group, 19 (15%) patients had synchronous lesions and 3 (2%) patients had subsequent lesions. In the TA group, 68 (43%) patients had synchronous lesions and 14 (9%) patients had subsequent lesions. The frequencies of patients with synchronous and subsequent lesions in the SA group were significantly lower than those in the TA group (p < 0.0001 and p = 0.02, respectively). The most frequent synchronous lesion was SA (67%) in the SA group and TA (95%) in the TA group. The most subsequent lesion was SA (62%) in the SA group and TA (100%) in the TA group. The histology of the index polyp and synchronous and subsequent lesions tended to be identical. No invasive colorectal carcinomas were observed in either group. Our data suggest that the colonic tumorigenesis potential of patients with SA may differ from that of patients with TA.


Adenoma/pathology , Colon/pathology , Colorectal Neoplasms/pathology , Rectum/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Polyps/pathology , Retrospective Studies
10.
J Bone Joint Surg Br ; 91(6): 823-9, 2009 Jun.
Article En | MEDLINE | ID: mdl-19483241

We evaluated the histological changes before and after fixation in ten knees of ten patients with osteochondritis dissecans who had undergone fixation of the unstable lesions. There were seven males and three females with a mean age of 15 years (11 to 22). The procedure was performed either using bio-absorbable pins only or in combination with an autologous osteochondral plug. A needle biopsy was done at the time of fixation and at the time of a second-look arthroscopy at a mean of 7.8 months (6 to 9) after surgery. The biopsy specimens at the second-look arthroscopy showed significant improvement in the histological grading score compared with the pre-fixation scores (p < 0.01). In the specimens at the second-look arthroscopy, the extracellular matrix was stained more densely than at the time of fixation, especially in the middle to deep layers of the articular cartilage. Our findings show that articular cartilage regenerates after fixation of an unstable lesion in osteochondritis dissecans.


Calcinosis/pathology , Knee Joint/pathology , Osteochondritis Dissecans/pathology , Adolescent , Arthroscopy , Child , Female , Fracture Fixation, Internal/methods , Humans , Knee Joint/surgery , Male , Osteochondritis Dissecans/surgery , Second-Look Surgery , Young Adult
11.
Endoscopy ; 41(4): 304-9, 2009 Apr.
Article En | MEDLINE | ID: mdl-19340732

BACKGROUND AND STUDY AIMS: Endoscopic mucosal resection (EMR) has been applied to the treatment of superficial esophageal squamous cell carcinoma (SCC). The incidence and characteristics of metachronous multiple esophageal SCCs and Lugol-voiding lesions (LVLs) were investigated in a retrospective study in patients who had undergone EMR for superficial esophageal SCC. PATIENTS AND METHODS: 96 patients with esophageal SCC who had been treated by EMR were followed up by endoscopy for 12 months or longer. Clinicopathologic parameters such as tumor size and location and presence of LVLs were examined. RESULTS: 10 patients (10 %) had synchronous multiple SCCs, and 12 (13 %) developed metachronous multiple SCCs. The mean annual incidence of newly diagnosed tumor was 4.4 %. The incidence of a speckled pattern of LVLs was 20/74 (27 %) in patients with solitary SCC, 5/10 (50 %) in synchronous multiple SCC, and 10/12 (83 %) in metachronous multiple SCC. The incidence of the presence of speckled pattern of LVLs was significantly higher in patients with multiple SCCs than in those with solitary SCC (68 % vs. 27 %, P = 0.0004). CONCLUSIONS: Patients who have undergone EMR for esophageal SCC, especially those with metachronous multiple LVLs in the background mucosa, should undergo follow-up with close endoscopic observation using Lugol staining.


Carcinoma, Squamous Cell/pathology , Coloring Agents , Esophageal Neoplasms/pathology , Esophagoscopy/methods , Iodides , Neoplasms, Multiple Primary/pathology , Neoplasms, Multiple Primary/surgery , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/surgery , Female , Humans , Incidence , Male , Middle Aged , Neoplasms, Multiple Primary/epidemiology , Retrospective Studies
12.
J Bone Joint Surg Br ; 90(3): 364-70, 2008 Mar.
Article En | MEDLINE | ID: mdl-18310762

We investigated the use of hypoxia-inducible factor (HIF) proteins as prognostic markers in chondrosarcoma and the relationship of HIF to the biological characteristics of cartilage tumours. The expression of HIF-1alpha, HIF-2alpha, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) were measured immunohistochemically in 29 specimens of cartilage tumour. There was no HIF-1alpha and HIF-2alpha staining in any of the nine benign cartilage tumours. In 20 specimens of chondrosarcoma, the rate of HIF-1alpha and HIF-2alpha expression was 40% and 25%, respectively. The tumour size (> or = 8 cm), histological grade (grade 2 and grade 3) surgical margin (marginal and intralesional) and HIF-1alpha expression (positive) correlated significantly with a shorter disease-free survival. There was a significant association between HIF-1alpha and the MVD and a strong trend towards a correlation between HIF-1alpha and the PCNA index or histological grade. Our findings suggest that HIF-1alpha protein may be a useful objective marker in the assessment of the prognosis in chondrosarcoma, since it plays an important role in tumour angiogenesis and cell proliferation.


Biomarkers, Tumor/analysis , Chondrosarcoma/metabolism , Chondrosarcoma/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Neoplasms, Connective Tissue/metabolism , Neoplasms, Connective Tissue/pathology , Adolescent , Adult , Aged , Basic Helix-Loop-Helix Transcription Factors/analysis , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Proliferation , Chondrosarcoma/blood supply , Disease-Free Survival , Female , Humans , Immunohistochemistry , Male , Microcirculation , Middle Aged , Neoplasms, Connective Tissue/blood supply , Neovascularization, Pathologic , Proliferating Cell Nuclear Antigen/analysis , Survival Analysis
13.
Acta Radiol ; 48(6): 672-7, 2007 Jul.
Article En | MEDLINE | ID: mdl-17611877

BACKGROUND: A schwannoma is a benign peripheral nerve tumor. Predicting the involvement of a nerve on symptoms or magnetic resonance (MR) findings is crucial to the diagnostic process. PURPOSE: To compare symptoms, MR findings, and histological findings between major-nerve schwannomas and intramuscular schwannomas. MATERIAL AND METHODS: Thirty-four patients with 36 palpable schwannomas (29 major-nerve schwannomas and seven intramuscular schwannomas) surgically excised and proven histologically were retrospectively reviewed. RESULTS: Frequencies of the Tinel-like sign, split-fat sign, entering and exiting nerve, and low-signal margin indicate the presence of a nerve, and were significantly higher in major-nerve schwannomas than in intramuscular schwannomas. In tumor morphological patterns (target sign, inhomogeneous and homogeneous pattern), there were no significant differences between major-nerve schwannomas and intramuscular schwannomas. Schwannomas showing the target sign histologically tended to be less degenerative. All major-nerve schwannomas and five of the intramuscular schwannomas produced some characteristic symptoms and/or MR findings, but two intramuscular schwannomas did not have any characteristic symptoms and findings. CONCLUSION: In major-nerve schwannomas, the Tinel-like sign, split-fat sign, entering and exiting nerve, and low-signal margin are commonly observed and useful for diagnosis. In intramuscular schwannomas, these characteristic findings are less common, which makes diagnosis difficult.


Muscle Neoplasms/diagnosis , Neurilemmoma/diagnosis , Peripheral Nervous System Neoplasms/diagnosis , Adult , Aged , Biopsy/methods , Contrast Media/administration & dosage , Diagnosis, Differential , Female , Gadolinium DTPA , Humans , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Muscle Neoplasms/pathology , Muscle Neoplasms/surgery , Neurilemmoma/pathology , Neurilemmoma/surgery , Observer Variation , Peripheral Nervous System Neoplasms/pathology , Peripheral Nervous System Neoplasms/surgery , Predictive Value of Tests , Retrospective Studies
14.
Am J Transplant ; 7(2): 347-55, 2007 Feb.
Article En | MEDLINE | ID: mdl-17229077

Tumor recurrence after liver transplantation still remains a significant problem in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated kinase (ROCK) pathway is involved in the motility and invasiveness of cancer cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway to promote the invasiveness of rat hepatocellular carcinoma cells. We also investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after experimental liver transplantation in a rat hepatocellular carcinoma model. Orthotopic liver transplantation was performed in hepatocellular carcinoma cell line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg, for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the cancer cell migration and stimulated phosphorylation of the myosin light chain (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor recurrence after liver transplantation and significant prolongation of survival were observed in the Y-27632-treated rats in comparison with theY-27632-untreated rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be used as a new antimetastatic agent for the prevention of tumor recurrence after liver transplantation.


Carcinoma, Hepatocellular/physiopathology , Immunosuppressive Agents/pharmacology , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Liver Neoplasms, Experimental/physiopathology , Liver Transplantation , Protein Serine-Threonine Kinases/antagonists & inhibitors , Tacrolimus/pharmacology , Amides/pharmacology , Animals , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/physiology , Cell Proliferation/drug effects , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Intracellular Signaling Peptides and Proteins/physiology , Liver Neoplasms, Experimental/therapy , Male , Neoplasm Invasiveness/physiopathology , Neoplasm Recurrence, Local/physiopathology , Neoplasm Recurrence, Local/prevention & control , Protein Serine-Threonine Kinases/physiology , Pyridines/pharmacology , Rats , Rats, Inbred BUF , Signal Transduction/drug effects , Signal Transduction/physiology , rho-Associated Kinases
15.
Acta Radiol ; 47(10): 1022-8, 2006 Dec.
Article En | MEDLINE | ID: mdl-17135003

PURPOSE: To evaluate whether portal vein embolization (PVE) using a mixture of gelatin sponge (GS) pieces and iodized oil is safe and effective in inducing hypertrophy of the future liver remnants (FLR). MATERIAL AND METHODS: PVE was performed in 14 patients (eight male and six female, mean age 65 years, range 35-81 years) diagnosed with malignant liver tumor before surgery, whose FLR volumes were judged too small to allow for safe resection. Liver volume change, biochemical data change, complications related to PVE, and postoperative complications were retrospectively evaluated. RESULTS: PVE was successful in all patients, and there were no procedural complications. Absolute FLR volume and FLR/total liver volume (TLV) ratio increased by 102 cm3 and 8% (mean values), respectively. Planned hepatectomies were cancelled in three patients due to extrahepatic metastasis or bile duct infection. Five of the 11 patients (45%) who underwent hepatectomies had major postoperative complications. However, complications due to hepatic failure were not seen. In 10 patients, except one whose outcome was fatal outcome, the mean hospitalization days with and without major complications were 73 and 33 days, respectively. CONCLUSION: PVE using a mixture of GS and iodized oil seems to be effective and safe in inducing hypertrophy of the FLR.


Embolization, Therapeutic/methods , Gelatin/therapeutic use , Hepatectomy , Iodized Oil/therapeutic use , Liver Neoplasms/surgery , Portal Vein , Preoperative Care , Adult , Aged , Aged, 80 and over , Female , Humans , Liver Neoplasms/diagnosis , Male , Middle Aged , Treatment Outcome
16.
Ann Oncol ; 17(8): 1213-20, 2006 Aug.
Article En | MEDLINE | ID: mdl-16760268

BACKGROUND: Hormone receptor (HR)-positive breast cancer cells grow through estrogen receptor (ER)-signaling pathways that mediate both genomic and nongenomic actions, which cross-talk with growth factors associated with resistance to tamoxifen. The aim of this study was to explore the cross-talk between extranuclear expression of ER and progesterone receptor (PR) and growth factor signaling pathways in primary breast cancer. PATIENTS AND METHODS: The extranuclear expression of ER and PR was examined in 219 primary breast cancers by immunohistochemical staining. Specimens showing such expression were further examined for the expression of pAkt and aromatase. Staining reactions were scored on the basis of intensity and distribution in the tumors. RESULTS: Extranuclear expression of ER or PR was observed in 21 cases (9.5%), which included four cases for ER and 20 cases for PR. Among these patients, HER-2, pAkt, and aromatase-positivity were observed in 14 cases (66.6%), 13 cases (61.9%), and 14 cases (66.6%), respectively. On the basis of nuclear HR expression, 11 of these cases were categorized as ER-positive/PR-negative, while two were ER-negative/PR-positive. Of these 13 cases, increased pAkt staining was found in 11 cases (84.6%). In particular, among the 11 ER-positive/PR-negative cases, elevated pAkt and aromatase were found in 10 (90.9%; P<0.01) and nine cases (81.8%), respectively. CONCLUSIONS: PR is expressed extranuclearly more frequently than ER in primary breast cancer, and extranuclear HRs cross-talk with the Akt/HER-2-signaling pathways and activation of aromatase. These observations may explain the more beneficial effects of aromatase inhibitors than tamoxifen for ER-positive/PR-negative patients.


Breast Neoplasms/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Aged , Aromatase/analysis , Aromatase/metabolism , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Cell Membrane/chemistry , Cell Membrane/metabolism , Cell Nucleus/chemistry , Cell Nucleus/metabolism , Female , Humans , Middle Aged , Proto-Oncogene Proteins c-akt/analysis , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis
17.
Eur J Surg Oncol ; 32(3): 269-77, 2006 Apr.
Article En | MEDLINE | ID: mdl-16431074

AIMS: Apoptosis, an early response cell death, is a useful marker for predicting tumour response after anticancer treatment; however, late-response cell death or nonapoptotic cell death, autophagy, can also be observed. This article reviews a rational model for predicting tumour response by assessing the influence of nonapoptotic cell death, and thereby developing a more efficient strategy for enhancing the therapeutic effect of anticancer treatment. METHOD: Literature search of clinical and experimental studies on "cell death and cancer" using established databases, including PUBMED. FINDINGS: Although induction of apoptosis may not contribute to overall tumour response, nonapoptotic cell death such as autophagy, which may be triggered by apoptosis, still occurs. Anticancer treatment-induced apoptosis is regulated by the balance of proapoptoic and antiapoptoic proteins through mitochondria, and resistance to apoptosis is mediated by Bcl-2-dependent and Akt-dependent pathways. Bcl-2 partially inhibits nonapoptotic cell death as well as apoptosis, whereas Akt inhibits both apoptotic and nonapoptotic cell death through several target proteins. CONCLUSIONS: Drug sensitivity is likely correlated with the accumulation of apoptotic and nonapoptotic cell deaths, which may influence overall tumour response in anticancer treatment. The ability to predict overall tumour response from the modulation of several important cell death-related proteins may result in a more efficient strategy for improving the therapeutic effect.


Antineoplastic Agents/therapeutic use , Apoptosis/physiology , Autophagy/physiology , Neoplasms/therapy , Animals , Apoptosis/drug effects , Apoptosis/radiation effects , Autophagy/drug effects , Autophagy/radiation effects , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/radiotherapy , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiotherapy, Adjuvant
18.
J Pathol ; 208(3): 319-26, 2006 Feb.
Article En | MEDLINE | ID: mdl-16261658

Various death triggers including DNA damage, oxidative stress, and growth factor deprivation promote the loss of mitochondrial membrane potential, leading to the production of reactive oxidative species (ROS) or enhanced permeability of the mitochondrial membrane, otherwise known as mitochondrial membrane permeabilization, by insertion of Bax/Bak into the outer membrane where it interacts with voltage-dependent anion channel (VDAC)/adenine nucleotide transporter (ANT). MMP leads to the release of small pro-apoptotic molecules, which induce caspase-dependent and -independent apoptotic cell death. The production of ROS due to the loss of mitochondrial membrane potential enhances the permeability of lysosomal membranes, resulting in the release of lysosomal proteases, which contribute to mitochondrial membrane permeabilization and the lysosomal degradation mechanism of autophagic cell death. Although defects in apoptotic and non-apoptotic cell death pathways can be carcinogenic, these pathways are more or less preserved within cancer cells and can therefore influence cell death and mediate resistance to cancer treatment. This paper discusses recent advances in determining the molecular mechanisms behind regulation of apoptotic and non-apoptotic cell death, as well as the interplay between these two processes, which may lead to the development of new strategies by which to enhance the therapeutic effects of chemotherapeutic agents.


Cells/pathology , Neoplasms/pathology , Animals , Apoptosis/physiology , Autophagy/physiology , Caspases/metabolism , Cell Death/physiology , Cell Membrane Permeability , Cells/metabolism , DNA Damage , Humans , Intracellular Membranes/metabolism , Membrane Potentials/physiology , Mitochondria/metabolism , Mitochondria/pathology , Neoplasms/metabolism , Reactive Oxygen Species/metabolism
19.
Int J Gynecol Cancer ; 15(6): 1187-90, 2005.
Article En | MEDLINE | ID: mdl-16343210

Villoglandular papillary adenocarcinoma (VGPA) of the uterine cervix is a rare neoplasm, and its treatment has rarely been reported. We report a patient with VGPA stage IIA responding to neoadjuvant chemotherapy with docetaxel (60 mg/m2 as an intravenous infusion) and cisplatin (70 mg/m2 as an intra-arterial infusion). At 3 weeks after completing one course of this regimen, the tumor size was reduced from 5.3 x 4.0 cm to 2.0 x 2.0 cm (81.1% reduction), revealed by computed tomography. Accordingly, the patient underwent radical hysterectomy, and there have been no signs of recurrence. Thus, the combination of docetaxel and cisplatin is suggested to be useful for neoadjuvant chemotherapy of cervical adenocarcinoma.


Adenocarcinoma, Papillary/drug therapy , Adenocarcinoma, Papillary/pathology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Adenocarcinoma, Papillary/surgery , Cisplatin/administration & dosage , Docetaxel , Female , Humans , Hysterectomy , Middle Aged , Neoadjuvant Therapy , Taxoids/administration & dosage , Treatment Outcome , Uterine Cervical Neoplasms/surgery
20.
Pathobiology ; 72(4): 220-4, 2005.
Article En | MEDLINE | ID: mdl-16127298

High frequencies of loss of heterozygosity (LOH) on chromosome 10p14-p15 have been reported in various tumors, including gliomas, pulmonary carcinoid tumors and cervical, hepatic, prostatic and esophageal carcinomas. However, LOH on chromosome 10p14-p15 in colorectal tumors has not been reported. Therefore, we examined LOH on chromosome 10p14-p15 in 60 colorectal carcinomas (21 superficial and 39 advanced types) by microsatellite assay. Three microsatellite loci, D10S191 (10p14), D10S558 and D10S249 (10p15) were examined by polymerase chain reaction [early colorectal carcinomas, LOH of markers D10S191 (36%), D10S558 (7%) and D10S249 (11%), and in advanced colorectal carcinomas, LOH of markers D10S191 (20%), D10S558 (13%) and D10S249 (33%)]. There were no significant associations between LOH on chromosome 10p14-p15 and clinicopathologic features, including patient age, sex, tumor location, depth of invasion, histologic type, lymph node metastasis and prognosis. These data suggest that a putative tumor suppressor gene associated with colorectal carcinogenesis may be located on chromosome 10p14-p15 and that alteration of this gene may be involved in the development but not progression of colorectal tumors.


Carcinoma/genetics , Chromosomes, Human, Pair 10 , Colorectal Neoplasms/genetics , Loss of Heterozygosity , Aged , Aged, 80 and over , Carcinoma/pathology , Colorectal Neoplasms/pathology , Female , Humans , Male , Microsatellite Repeats , Middle Aged , Time Factors
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