Biomedical subjects

Nobuyuki Yamamoto

Publications and source records attributed to Nobuyuki Yamamoto.

At least 19 recordsLinked to original sources

PubMed2026

Sequential Immune Activation of Effector T Cells as Biomarkers of Response to Durvalumab in Patients with Locally Advanced NSCLC.

PURPOSE: Durvalumab therapy following concurrent chemoradiotherapy (cCRT) improves progression-free survival (PFS) in patients with unresectable locally advanced non-small cell lung cancer. In this prospective observational study, we evaluated the changes in peripheral blood immune cell counts to elucidate the immunologic mechanisms underlying cCRT and durvalumab therapy. EXPERIMENTAL DESIGN: Peripheral blood mononuclear cell (PBMC) samples were collected at four time points: before cCRT, after cCRT, at the start of durvalumab, and 8 weeks after the start of durvalumab, and analyzed by multicolor flow cytometry. RESULTS: Of the 149 enrolled patients, 115 received durvalumab consolidation therapy after cCRT. The median PFS in the overall population was 24.2 months, and the 3-year PFS rate was 38.9%. PBMC analysis showed an increased effector fraction of CD4+ T cells before and after cCRT but no change in CD8+ T cells. Following durvalumab therapy, the effector fraction ratio of CD8+ T cells (CD62Llow CD8+ T cells) increased and positively correlated with increased CD62Llow CD4+ T cells during cCRT. Patients whose proportion of CD62Llow CD4+ T cells exceeded the threshold for cCRT had better PFS than those below the threshold. Patients whose CD62Llow CD8+ T-cell proportion exceeded the threshold after durvalumab therapy showed prolonged PFS compared with those below the threshold. CONCLUSIONS: cCRT promotes an increase in effector CD4+ T cells, and the subsequent increase in CD8+ T cells following durvalumab therapy prolongs PFS. Peripheral blood effector-type CD4+ and CD8+ T cells are potential biomarkers for evaluating the immune status of patients and predicting treatment efficacy.

Humans↗

PubMed2025

A Single-Arm Phase 2 Study of Sotorasib Plus Carboplatin and Pemetrexed in Patients With Advanced Nonsquamous NSCLC With KRAS G12C Mutation (WJOG14821L, SCARLET).

INTRODUCTION: The efficacy and safety of sotorasib plus platinum doublet chemotherapy in KRAS G12C-mutated nonsquamous NSCLC (nonsq NSCLC) have been previously reported with a limited follow-up period. METHODS: SCARLET is a single-arm phase 2 study involving chemotherapy-naive patients with KRAS G12C-mutated nonsq NSCLC. The participants received 960 mg daily plus four cycles of carboplatin (area under the curve = 5)/pemetrexed 500 mg/m2, followed by sotorasib/pemetrexed until disease progression. The primary end point was the overall response rate (ORR) and the secondary end points were progression-free survival (PFS), overall survival, and safety. Using plasma samples, next-generation sequencing was performed at baseline, 3 weeks, and during disease progression (the Japan Registry of Clinical Trials number 2051210086). RESULTS: Thirty patients were enrolled between October 2021 and July 2022 with a median follow-up of 14.8 months. ORR was 88.9% (80% confidence interval [CI]: 78.5%-94.8%, 95% CI: 70.8%-97.6%), median PFS was 6.6 months (95% CI: 5.3-16.7 mo), and median overall survival was 20.6 months (95% CI: 8.1 mo-not estimated). Among patients with programmed death-ligand 1 expression levels of 1% or higher and less than 1%, the ORRs were 82.3 and 100%, respectively, and the median PFS was 7.6 and 9.7 months, respectively. Using plasma samples, patients without KRAS G12C at baseline, without KRAS-related pathway co-alterations, or who cleared KRAS G12C at 3 weeks had better median PFS (16.7, 13.9, 8.7 mo, respectively). Tumor protein 53 mutations and EGFR and MET amplification were detected as acquired resistance. CONCLUSIONS: In patients with KRAS G12C-mutated nonsq NSCLC, sotorasib plus carboplatin/pemetrexed reported favorable efficacy, particularly for patients with less than 1% programmed death-ligand 1, with manageable toxicity.

Humans↗

PubMed2006

Effect of rotator interval closure on glenohumeral stability and motion: a cadaveric study.

The effect of rotator interval closure, which is performed as an adjunct to arthroscopic stabilization of the shoulder, has not been clarified. Fourteen fresh-frozen cadaveric shoulders were used. The position of the humeral head was measured using an electromagnetic tracking device with the capsule intact, sectioned, and imbricated between the superior glenohumeral ligament and the subscapularis tendon (SGHL/SSC closure) or between the superior and middle glenohumeral ligaments (SGHL/MGHL closure). The direction of translational loads (10, 20, and 30 N) and arm positions were (1) anterior, posterior, and inferior loads in adduction; (2) anterior load in abduction/external rotation in the scapular plane; and (3) anterior load in abduction/external rotation in the coronal plane. The range of motion was measured using a goniometer under a constant force. Both methods reduced anterior translation in adduction. Only SGHL/MGHL closure reduced anterior translation in abduction/external rotation in the scapular plane and posterior translation in adduction. Both methods reduced the range of external rotation and horizontal abduction. Rotator interval closure is expected to reduce remnant anterior/posterior instability and thereby improve the clinical outcomes of arthroscopic stabilization procedures.

Adult↗

PubMed2006

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104.

BACKGROUND: Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS: One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS: Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS: Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study.

Adult↗

PubMed2006

Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib.

PURPOSE: Interstitial lung disease (ILD) is a serious adverse effect of gefitinib, but its prevalence and risk factors remain largely unknown. We examined the prevalence of and risk factors for gefitinib-induced ILD associated with practical use of the drug in Japanese with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Clinical information was retrospectively assembled for NSCLC patients who started gefitinib treatment at affiliated institutions of the West Japan Thoracic Oncology Group between August 31 and December 31, 2002. Medical records of patients who developed pulmonary infiltrates were reviewed by a central committee of extramural experts for identification of patients with gefitinib-induced ILD. Multivariate logistic or Cox regression analysis was performed to identify independent predictive factors for ILD, antitumor response, and survival. RESULTS: Seventy cases of and 31 deaths from gefitinib-induced ILD were identified among 1,976 consecutively treated patients at 84 institutions, corresponding to a prevalence of 3.5% and mortality of 1.6%. Gefitinib-induced ILD was significantly associated with male sex, a history of smoking, and coincidence of interstitial pneumonia (odds ratios = 3.10, 4.79, and 2.89, respectively). Predictive factors for response were female sex, no history of smoking, adenocarcinoma histology, metastatic disease, and good performance status (PS), whereas predictive factors for survival were female sex, no history of smoking, adenocarcinoma histology, nonmetastatic disease, good PS, and previous chest surgery. CONCLUSION: ILD is a serious adverse effect of gefitinib in the clinical setting that cannot be ignored. However, patient selection based on sex and smoking history can minimize ILD risk and maximize the clinical benefit of gefitinib.

Adult↗

PubMed2006

Imaging of gefitinib-related interstitial lung disease: multi-institutional analysis by the West Japan Thoracic Oncology Group.

Gefitinib (Iressatrade mark) is an epidermal growth factor receptor tyrosine kinase inhibitor that has been approved for the treatment of lung cancer in Japan, however, after marketing several cases of severe pulmonary toxicity were reported. The West Japan Thoracic Oncology Group conducted an independent survey of acute pulmonary toxicity and interstitial lung disease (ILD) caused by gefitinib in its member's institutions. The purpose of this study was to clarify the image characteristics of ILD caused by the molecular-targeting drug gefitinib. A total of 1976 patients had been treated with gefitinib between August and December 2002, and 102 of them were suspected of having acute pulmonary toxicity and ILD. A final definite diagnosis of gefitinib-induced ILD was made by at least three radiologists based on a review and analysis of the chest radiography and CT findings plus the clinical data in the medical records. The imaging findings were classified into four patterns: (A) a nonspecific area with ground-glass attenuation, (B) a multifocal area of airspace consolidations, (C) patchy distribution of ground-glass attenuation accompanied by interlobar septal thickening, and (D) extensive bilateral ground-glass attenuation or airspace consolidations with traction bronchiectasis. CT as well as chest radiography had been performed in 65 of the 102 patients at the onset of ILD, and chest radiography alone had been performed in 26. After excluding 11 cases with insufficient data and 21 cases concluded to be other pulmonary diseases, 70 patients were diagnosed with gefitinib-induced ILD. Finally, the diagnostic image findings were classified as pattern A in 29 cases, pattern B in 7 cases, pattern C in 3 cases, pattern D in 20 cases and others in 11 cases. The CT images were classified as pattern A, B, C, and D in 24, 7, 1, and 12 cases, respectively. The mortality rate was significantly higher in the patients with pattern D than the other patterns. Pattern D were thought to represent the features of diffuse alveolar damage. In conclusion, the molecular-targeting drug gefitinib induces pulmonary toxicity at a certain rate and the imaging findings of ILD induced by gefitinib are similar to those of pulmonary toxicity induced by conventional antineoplastic agents.

Adult↗

PubMed2006

The effect of the inferior capsular shift on shoulder intra-articular pressure: a cadaveric study.

BACKGROUND: The inferior capsular shift procedure is commonly performed for multidirectional instability of the shoulder with excellent clinical results. HYPOTHESIS: The mechanism of this procedure is to increase shoulder stability by changing the responsiveness of intra-articular pressure to downward loading. STUDY DESIGN: Controlled laboratory study. METHODS: In 7 fresh-frozen cadaveric shoulders, inferior capsular shift was simulated by imbricating the anterior and posterior capsule using clamps. The position was monitored using an electromagnetic tracking device with the glenohumeral joint capsule intact, imbricated anteriorly, or imbricated anteriorly and posteriorly and with the inferior load of 0, 0.5, or 1.0 kg. Simultaneously, intra-articular pressure was monitored using a pressure transducer. Saline was injected into the glenohumeral joint to measure capsular volume. The capsule was vented, and the position was again measured. RESULTS: Intra-articular pressure was -71 +/- 19, -221 +/- 70, and -366 +/- 73 cm H(2)O with 0, 0.5, and 1.0 kg of load, respectively, with the capsule intact. With anterior imbrication, intra-articular pressure decreased to -79 +/- 10, -274 +/- 103, and -460 +/- 135 cm H(2)O, respectively, and with anterior and posterior imbrication, intra-articular pressure further decreased to -87 +/- 16, -308 +/- 74, and -548 +/- 39 cm H(2)O, respectively. The volume of the intact shoulder (36 +/- 9 mL) significantly decreased to 27 +/- 7 mL (75%) with anterior imbrication and to 15 +/- 5 mL (42%) with anterior and posterior imbrications (P = .0001). Before venting the capsule, inferior displacement was 5% of the vertical length of the glenoid, even with 1.0 kg of load with any capsular conditions. After venting, the humeral head dislocated inferiorly in all shoulders, even after imbrications. CONCLUSION: The inferior capsular shift procedure decreases joint volume and increases responsiveness of intra-articular pressure to downward loading. CLINICAL RELEVANCE: Biomechanical data provide scientific background to the commonly performed procedures of inferior capsular shift and thermal capsular shrinkage.

Adult↗

PubMed2006

Phase I/II study of weekly docetaxel dose escalation in combination with fixed weekly cisplatin and concurrent thoracic radiotherapy in locally advanced non-small cell lung cancer.

PURPOSE: We conducted a phase I study to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly docetaxel and cisplatin (DOC/CDDP) with concurrent thoracic radiotherapy (TRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The DOC/CDDP administration schedules consisted of a split schedule (SS) with administration in 3 out of every 4 weeks, and a continuous schedule (CS) with administration every week. TRT was given to a total dose of 60 Gy at 2 Gy per fraction over 6 weeks. RESULTS: Twenty-one patients entered the study. The patient characteristics were: PS 0/1/2, 6/13/2; Sq/Ad, 16/5; stage IIIA/IIIB, 4/17. The principal DLT was grade3 esophagitis. The MTD of DOC on the SS and CS in combination with CDDP (25 mg/m2/week) was 25 and 20 mg/m(2)/week, respectively. We determined the RD and schedule of DOC/CDDP on the SS to be 20/25 mg/m(2)/week. The serum alpha-1-acid glycoprotein (AAG) concentration values were found to be negatively correlated with the grade of esophagitis. The median survival time was 23.1 months. CONCLUSION: The chemoradiation regimen tested in this study has promising activity and manageable toxicity. The continuous schedule could not be recommended due to excessive toxicity. The main DLT was esophagitis, and it significantly correlated with the plasma AAG concentration.

Aged↗

PubMed2006

Objective evaluation of shoulder pain by measuring skin impedance.

The subjective nature of pain has made its objective evaluation rather difficult. Recently, skin impedance was reported to reflect pain. The purpose of this study was to determine the usefulness of measuring skin impedance in evaluating shoulder pain. Fifty-three patients with shoulder pain were examined. Skin impedance was measured by a skin impedance meter in three different conditions and was compared with the visual analog scale recorded at the same time.

Adult↗

PubMed2005

Are pain location and physical examinations useful in locating a tear site of the rotator cuff?

BACKGROUND: Pain is the most common symptom of patients with rotator cuff tendinopathy, but little is known about the relationship between the site of pain and the site of cuff pathologic lesions. Also, accuracies of physical examinations used to locate a tear by assessing the muscle strength seem to be affected by the threshold for muscle weakness, but no studies have been reported regarding the efficacies of physical examinations in reference to their threshold. HYPOTHESIS: Pain location is useful in locating a tear site. Efficacies of physical examinations to evaluate the function of the cuff muscles depend on the threshold for muscle weakness. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The authors retrospectively reviewed the clinical charts of 160 shoulders of 149 patients (mean age, 53 years) with either rotator cuff tears (140 shoulders) or cuff tendinitis (20 shoulders). The location of pain was recorded on a standardized form with 6 different areas. The diagnostic accuracies of the following tests were assessed with various thresholds for muscle weakness: supraspinatus test, the external rotation strength test, and the lift-off test. RESULTS: Lateral and anterior portions of the shoulder were the most common sites of pain regardless of existence of tear or tear location. The supraspinatus test was most accurate when it was assessed to have positive results with the muscle strength less than manual muscle testing grade 5, whereas the lift-off test was most accurate with a threshold less than grade 3. The external rotation strength test was most accurate with a threshold of less than grade 4+. CONCLUSION: The authors conclude that pain location is not useful in locating the site of a tear, whereas the physical examinations aiming to locate the tear site are clinically useful when assessed to have positive results with appropriate threshold for muscle weakness.

Adolescent↗

PubMed2005

Contact area, contact pressure, and pressure patterns of the tendon-bone interface after rotator cuff repair.

BACKGROUND: The contact pressure and contact area at the tendon-bone interface after the most commonly used rotator cuff repair methods have not been investigated. HYPOTHESIS: There are no significant differences among the transosseous, the single-row suture anchor, and the double-row suture anchor techniques in terms of contact pressure, contact area, and pressure patterns at the tendon-bone interface. STUDY DESIGN: Controlled laboratory study. METHODS: After creating a full-thickness supraspinatus tendon tear in 10 cadaveric shoulder specimens, we inserted pressure-sensitive film between the tendon stump and the bone, and we repaired the tear by (1) transosseous, (2) single-row suture anchor, and (3) double-row suture anchor techniques. RESULTS: The contact area of the double-row technique was 42% greater than that of the transosseous technique (P < .0001) and 60% greater than that of the single-row technique. The contact area of the transosseous technique was 31% greater than that of the single-row technique (P = .0015). The average pressures of the single-row and double-row techniques were 18% (P = .014) and 16% (P = .03) greater, respectively, than that of the transosseous technique, but there was no significant difference between the single-row and double-row techniques (P = .915). CONCLUSIONS: The double-row technique produced the greatest contact area and the second-highest contact pressure, whereas the single-row technique created the highest contact pressure and the least contact area. The transosseous technique produced the second-greatest contact area and the least contact pressure. CLINICAL RELEVANCE: The double-row suture anchor technique and the transosseous technique may provide a better environment for tendon healing.

Absorbable Implants↗

PubMed2005

Location of the glenoid defect in shoulders with recurrent anterior dislocation.

BACKGROUND: In patients with recurrent anterior dislocations of the shoulder, it is well known that the glenoid rim is often deficient (8%-95%). However, little is known regarding the precise location of the bony defect of the glenoid. HYPOTHESIS: The bony defect is anterior rather than anteroinferior to the glenoid. STUDY DESIGN: Cohort study (symptom prevalence); Level of evidence, 2. METHODS: The authors studied 3-dimensional images of the glenoid reconstructed from computed tomography to determine the location of the glenoid defect in 123 shoulders of 123 patients with recurrent anterior dislocations of the shoulder. They measured the location, extent, and orientation of the defect based on the clock face of the glenoid. RESULTS: The defects were located between 12:08 and 6:32, with the range between 2:30 and 4:20 being the most frequent. The extent of the glenoid defect was 106.7 degrees +/- 27.1 degrees (mean +/- standard deviation). The mean orientation of the defect was pointing toward 3:01 on the clock face of the glenoid, at a mean angle of 90.5 degrees +/- 10.4 degrees from the 12-o'clock direction. CONCLUSION: The glenoid defect is located almost anterior to the glenoid.

Adolescent↗

PubMed2005

Attachment types of the long head of the biceps tendon to the glenoid labrum and their relationships with the glenohumeral ligaments.

PURPOSE: To clarify the attachment types of the long head of the biceps tendon to the glenoid labrum and their relationships with the glenoid attachment of the glenohumeral ligaments. TYPES OF STUDY: Anatomic study in cadavers. METHODS: Using 101 cadaver shoulders, the glenoid attachment types of the biceps tendon and the location of the glenoid origin of the glenohumeral ligaments were assessed macroscopically and then histologically on the sagittal section. RESULTS: The glenoid attachment types of the biceps tendon were defined as entirely-posterior in 28 shoulders (27.7%), posterior-dominant in 56 shoulders (55.4%), equal in 17 shoulders (16.8%), and entirely anterior in none (0%). In all shoulders, the superior and middle glenohumeral ligaments were attached between 12 and 1 o'clock (average, 12:36 o'clock), whereas the inferior glenohumeral ligament (IGHL) showed greater variation. In the posterior-dominant and equal types, the IGHL was attached relatively high (average 2:49 o'clock for the posterior-dominant type and 1:49 o'clock for the equal type). In the entirely posterior type, the IGHL was attached low, between 4 and 5 o'clock (average, 4:32 o'clock). There was a significant difference between them (P < .001). Histologic examination showed that in the posterior-dominant and equal types, the fibers of the IGHL directly linked to the fibers of the biceps tendon, whereas in the entirely posterior type no such direct connections were observed. However, in all types, the fibers of the biceps tendon were attached to the posterior labrum. CONCLUSIONS: The labral attachment of the long head of biceps tendon was posterior regardless of its macroscopic appearance. The macroscopic attachment pattern of the biceps tendon resulted from the different attachment height of the IGHL. The attachment site of the IGHL is lower than 4 o'clock in the entirely posterior type, whereas it is higher than 4 o'clock in other types. CLINICAL RELEVANCE: The present study provides useful information about the original attachment site of the IGHL during Bankart repair.

Anthropometry↗

PubMed2005

Cross-sectional area of the tendon and the muscle of the biceps brachii in shoulders with rotator cuff tears: a study of 14 cadaveric shoulders.

BACKGROUND: The intraarticular portion of the long head of the biceps tendon is often widened in shoulders with cuff tears. It is unclear whether this is a local phenomen or is caused by muscle hypertrophy. METHODS: We investigated morphological changes of the biceps brachii in 14 embalmed shoulders: 7 with intact rotator cuff and 7 with rotator cuff tears. We measured the cross-sectional area (CSA) of the tendon of the long head of the biceps (LHB) at 9 levels between the glenoid origin and the musculotendinous junction. The muscle volume and the muscle fiber length of the long and short heads of the biceps were measured to calculate the physiological CSA (PCSA) by dividing the volume by the fiber length. RESULTS: The CSA of the LHB tendon at the entrance to the bicipital groove was greater in cuff tear shoulders than in normal shoulders. The PCSA of the biceps was similar in normal and cuff tear shoulders. INTERPRETATION: Hypertrophy of the LHB tendon appears to be a localized morphological change near the entrance to the bicipital groove.

Aged↗

PubMed2005

Unusual late pulmonary complication in a child after umbilical cord blood transplantation: high-resolution CT-pathologic correlation.

We encountered a late pulmonary complication after umbilical cord blood transplantation (UCBT) that has not been previously reported. High-resolution CT (HRCT) findings of this disease were compared with the pathology. HRCT obtained on inspiration showed dilated thick-walled bronchioli, and innumerable centrilobular linear and branching structures in the bilateral middle and lower lobes. Neither mosaic perfusion nor air-trapping was seen in HRCT on inspiration and expiration. These HRCT findings were atypical compared with those of former bronchiolitis obliterans (BO) after bone marrow transplant (BMT). Pathologic specimens obtained by open lung biopsy showed thickening of the wall from the distal bronchioli to the alveolar ducts due to submucosal and intraepithelial infiltration of lymphocytes, histiocytes and foamy macrophages, which was not accompanied by organizing changes. These changes resemble lymphocytic bronchiolitis in lung transplant recipients, which was well correlated with HRCT findings. We think that our case was a new late pulmonary complication after UCBT.

Adolescent↗

PubMed2005

Arch reconstruction without circulatory arrest in neonates.

Between May 2000 and December 2002, 10 neonates underwent arch reconstruction without circulatory arrest. Age at surgery ranged from 1 to 18 days, and body weight ranged from 1.62 to 3.38 kg. The diagnosis was interrupted aortic arch in 4, hypoplastic left heart syndrome in 3, and coarctation complex in 3. A 3 mm polytetrafluoroethylene graft was anastomosed to the innominate artery, and the brain was perfused via this graft while the aortic arch was reconstructed. Regional cerebral oxygen saturation and the right and left radial artery pressures were monitored. There were 2 deaths: one because of low cardiac output syndrome after a Norwood operation; another from multiple organ failure due to preoperatively undetected congenital biliary atresia. Regional cerebral oxygen saturation was kept constant at over 40% during regional cerebral perfusion. There were no neurologic sequelae observed postoperatively. It was concluded that the regional cerebral perfusion technique can be safely applied during neonatal aortic arch reconstruction, and deep hypothermic circulatory arrest should be avoided.

Anastomosis, Surgical↗

PubMed2004

Predominant role of basicity of leaving group in alpha-effect for nucleophilic ester cleavage.

It has been found that alpha-effects in nucleophilic reactions, unexpectedly large nucleophilicity due to adjacent unpaired electrons, are strongly dependent on the structure of substrate. The nucleophilic cleavages of 4-nitrobenzoate esters and 4-methylbenzoate esters by HOO- have been systematically investigated in detail. When the leaving groups of substrates are sufficiently good (aryl, 2,2,2-trifluoroethyl, and 2,2-dichloroethyl esters), alpha-effect is evident. However, this effect drastically decreases as the leaving group gets poorer, and is only marginal for the cleavages of 2-fluoroethyl and methyl esters. In the nucleophilic cleavages by salicylaldoxime and acetohydroxamic acid, alpha-effect is also notable only for the esters having good leaving groups. These enormous dependences of alpha-effects on the substrate-structure have been interpreted in terms of the difference in the position of transition-state in the reaction coordinate.

Benzoates↗

PubMed2004

[Anti angiogenesis].

Based on presentations on the basic concepts and scientific rationale of anti-angiogenic approaches to cancer therapy and the possible applications in the area of prostate cancer, gastrointestinal cancer, lung cancer and breast cancer it is easy to conclude that development of anti-angiogenic approaches into clinical therapies is extremely challenging. It is now well established that cancer growth is increased by angiogenic factors and that inhibition of angiogenesis decreases growth and metastatic potential. Anti-angiogenic effect can be obtained through interference with multiple targets. Further development of new strategies involving such novel cancer therapies requires wide reaching development of translational research abilities. However, for moving new therapies into the clinic same rigorous criteria need to be applied as is done for traditional therapies. Angiogenesis appear to be a critical factor for development of prostate, gastric, lung and breast cancers. Development of new anti-angiogenic treatment modalities might become very important in these diseases. A critical requirement for the successful clinical development will be the development of imaging techniques that can help evaluate the effect on blood vessel functionality. Such surrogate markers of anti-angiogenic effect will be essential for optimising molecules and doses.

Angiogenesis Inhibitors↗