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Biomedical subjects

Moshe Inbar

Publications and source records attributed to Moshe Inbar.

At least 19 recordsLinked to original sources
PubMed2006

ErbB4 increases the proliferation potential of human lung cancer cells and its blockage can be used as a target for anti-cancer therapy.

Clinical and experimental data suggest that ErbB-4, a member of the epidermal growth factor receptor family, may have a role in cancer progression and response to treatment. We found recently, using a retrospective clinical analysis, that expression of ErbB-4 receptor is correlated with metastatic potential and patient survival in non-small-cell lung cancer (NSCLC). The purpose of this work was to correlate the expression of the ErbB-4 and lung cancer cells growth in vitro and in vivo and to determine the therapeutic potential of a monoclonal antibody to ErbB-4 against lung cancer. For this aim, we ectopically expressed ErbB-4 in a human NSCLC cell line that did not express the ErbB-4 protein. Overexpression of ErbB-4 produced a constitutively activated ErbB-4 receptor. The transfected ErbB-4 positive clones showed an increased cell proliferation in vitro and in vivo in comparison with parental ErbB-4 negative cells and with the cells transfected by neomycin-resistant gene. A monoclonal antibody to ErbB-4 showed both an inhibitory effect on growth rate and an increasing apoptotic rate in the cells expressing ErbB-4. The results of the current study provide evidence that ErbB-4 plays a significant role in human lung cancer and may serve as a molecular target for anticancer therapy.

Adenocarcinoma↗
PubMed2006

The effects of nectar-nicotine on colony fitness of caged honeybees.

Nectar of many bee flowers contains secondary compounds, which are considered toxic for honeybees on repeated exposure. Although many anecdotal reports indicate the toxicity of secondary compounds to bees, only a few studies have tested the extent of toxicity at different honeybee ages, especially at the larval stages. Honeybees encounter nicotine at trace concentrations (between 0.1 and 5 ppm) in floral nectar of a few Nicotiana spp. and in Tilia cordata. Adult honeybee workers tolerate these nicotine concentrations. In controlled nonchoice feeding experiments with caged bees, we investigated the effect of nicotine on hatching success and larval and forager survival. Naturally occurring concentrations of nectar-nicotine did not affect hatching success of larvae or their survival, but the latter was negatively affected by higher concentrations of nicotine (50 ppm). Concentrations of nicotine in fresh honey samples from the hives were 90% lower than the concentrations in the offered experimental sucrose solutions. Our results indicate that honeybees can cope with naturally occurring concentrations of nicotine, without notable mortality, even when consumed in large quantities for more than 3 weeks.

Animals↗
PubMed2006

The presentation of malignant tumours and pre-malignant lesions incidentally found on PET-CT.

PURPOSE: The purpose of the study was to determine the general and organ-specific presentation of incidental primary tumours on PET-CT. METHODS: PET-CT reports of 2,360 consecutive patients were reviewed and revealed 156 lesions suspicious for a new unexpected malignancy, in 151 patients. One hundred and twenty of these lesions, in 115 patients, were further assessed, by biopsy (n=84 patients) or by clinical and imaging follow-up (n=31 patients) for a mean of 17+/-4 months (range 12-25 months). RESULTS: Forty-four unexpected malignancies were found in 41 of the study patients (1.7%). Twenty-seven of the 44 incidental tumours were identified on the basis of their location, which was uncommon for metastasis of the known malignancy. Eight were detected as a result of either the difference in FDG avidity of the known malignancy and the incidental lesion or the presence of an incidental non-FDG-avid mass on the CT part of the study. Four tumours were synchronous carcinomas in patients with known colorectal malignancy, three were identified by virtue of the discordant response to treatment compared with the known primary tumour and two were detected as new sites of disease after a prolonged disease-free period. There was organ variability in the positive predictive values (PPV) of PET-CT findings for incidental primary malignancy or pre-malignant lesions: 62% for colonic lesions, 54% for lung lesions and 24% for thyroid lesions. CONCLUSION: Incidental primary tumours may be identified on PET-CT based on their location, FDG avidity, response to therapy and time of appearance. The PET and CT parts of the study appear to complement each other and assist in identification of these incidental tumours.

Adult↗
PubMed2006

Can rectal cancers with pathologic T0 after neoadjuvant chemoradiation (ypT0) be treated by transanal excision alone?

BACKGROUND: Patients with rectal cancer who have complete rectal wall tumor regression after neoadjuvant chemoradiation probably have eradication of tumor cells in the mesorectum as well, thus raising the possibility of transanal excision. METHODS: All pathology reports of all patients with locally advanced low and mid rectal cancer who underwent preoperative chemoradiation followed by radical resection from May 2000 to June 2004 were reviewed to evaluate the correlation between complete tumor response (ypT0) and nodal response. RESULTS: One hundred one consecutive patients had neoadjuvant chemoradiation followed by definitive operation. Four were excluded, leaving 64 men and 33 women (median age, 62 years). Fifty-three patients (55%) had mid rectal cancer, and 44 (45%) had low rectal cancer. Fifty-eight patients (60%) underwent low anterior resection, and 36 (37%) underwent abdominoperineal resection. In 17 patients (18%), no residual tumor cells were present within the rectal wall. One patient (6%) with ypT0 disease had positive lymph nodes. CONCLUSIONS: No residual tumor in the rectal wall correlates with the absence of viable cancer cells in the mesorectal tissue (94%). Approximately 10% of T1 tumors have involved lymph nodes, and local excision is an accepted option. Transanal excision could probably be considered in a highly selected group of patients with a mural pathologic complete response to neoadjuvant therapy. This approach should be prospectively investigated, and strict selection guidelines should be used.

Adult↗
PubMed2006

Heavily pretreated ovarian cancer patients treated by single-agent gemcitabine. A retrospective outcome comparison between platinum-sensitive and platinum-resistant patients.

To assess activity and toxicity of gemcitabine treatment in heavily pretreated epithelial ovarian cancer (EOC) patients and compare the outcome between platinum-sensitive and platinum-resistant patients. We conducted a retrospective analysis of 43 women with EOC treated with gemcitabine on Days 1, 8 and 15 every 28 days. Response was evaluated by physical examination and serial CA 125 measurements. The patients (median age 62 years, range 29-87) were previously exposed to a median of 3 (2-8) chemotherapy regimens. A median of 3.5 (1-14) gemcitabine cycles were administered. Eleven (25.6%) patients showed partial response, 19 (44.2%) had stable disease and 13 (30.2%) progressed. Among 22 platinum-sensitive and 21 platinum-resistant patients, the response rate was 45.5% and 4.7% respectively (p = 0.001), and the median time to progression was 5.0 and 2.8 months, respectively (p = 0.0006). The respective median survival was 16.5 and 6.3 months (p = 0.0001). Grade III-IV hematological toxicities included anemia in four (9.3%) patients, thrombocytopenia in four (9.3%) and leucopenia in two (4.7%). The main non-hematological toxicities were grade III fatigue in two patients (4.7%) and nausea and vomiting in two (4.7%). Single agent gemcitabine is an attractive option for heavily pretreated EOC patients. The significant difference between platinum-sensitive and resistant patients' warrants further investigation.

Adenocarcinoma, Clear Cell↗
PubMed2006

[Brachytherapy combined with external beam radiation in localized prostate cancer].

BACKGROUND & RATIONALE: A combination of brachytherapy with external beam radiotherapy is one treatment option for localized moderately to poorly differentiated prostate cancer. This article presents initial Israeli experience with this treatment option. METHODS: In the last 6 years, 56 men were treated with a combination of internal brachytherapy, external beam radiation and 6 months adjuvant hormonotherapy. All were prospectively followed while using validated questionnaires to assess urinary morbidity and sexual function. RESULTS: Treatment was well tolerated by all. None had grade 2-3 rectal morbidity. Mild to moderate urinary morbidity was seen in most, not different than seen in radiation therapy when given as monotherapy. Sexual function was only mildly affected. Biochemical NED (PSA based) rates albeit for a rather short follow-up period, were similar to those seen when utilizing other radical treatment options. CONCLUSIONS: Combining I125-brachytherapy with external beam radiation together with a short course of hormonotherapy results in acceptable morbidity and good biochemical outcome. This option should be offered to selected patients with higher grade localized prostate cancer, when other options are less optimal.

Aged↗
PubMed2005

Feeding responses of free-flying honeybees to secondary compounds mimicking floral nectars.

The role of secondary compounds (SC) in deterring herbivores and pathogens from vegetative parts of plants is well established, whereas their role in plant reproductive organs such as floral nectar is unclear. The present study aimed to reveal the response of free-flying honeybees to naturally occurring concentrations of four SC in floral nectar. We selected nicotine, anabasine, caffeine, and amygdalin, all of which are found in nectar of various plants. In repeated paired-choice experiments, we offered 20% sucrose solution as control along with test solutions of 20% sucrose with various concentrations of the above SC. Except for anabasine, naturally occurring concentrations of SC did not have a deterring effect. Furthermore, low concentrations of nicotine and caffeine elicited a significant feeding preference. SC can, therefore, be regarded as postingestive stimulants to pollinators, indicating that the psychoactive alkaloids in nectar may be a part of their mutualistic reward. Further studies are needed to test our hypothesis that psychoactive alkaloids in nectar impose dependence or addiction effects on pollinators.

Animals↗
PubMed2005

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.

BACKGROUND: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. METHODS: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. RESULTS: Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. CONCLUSIONS: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)

Adult↗
PubMed2005

Conspicuous and aposematic spines in the animal kingdom.

Spines serve as a common physical defence mechanism in both the plant and animal kingdoms. Here we argue that as in plants, defensive animal spines are often conspicuous (shape and colour) and should be considered aposematic. Conspicuous spines may evolve as signals or serve as a cue for potential predators. Spine conspicuousness in animals has evolved independently across and within phyla occupying aquatic and terrestrial ecosystems, indicating that this convergent phenomenon is highly adaptive. Still, many spines are cryptic, suggesting that conspicuity is not simply constrained by developmental factors such as differences in the chemical composition of the integument. Aposematism does not preclude the signalling role of conspicuous spines in the sexual arena.

Animals↗
PubMed2005

Gemcitabine, epirubicin, and paclitaxel versus fluorouracil, epirubicin, and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: a Central European Cooperative Oncology Group International, multicenter, prospective, randomized phase III trial.

BACKGROUND: The objectives of this phase III trial were to compare the time to progressive disease (TtPD), overall response rate (ORR), overall survival, and toxicity of gemcitabine, epirubicin, and paclitaxel (GET) versus fluorouracil (FU), epirubicin, and cyclophosphamide (FEC) as first-line therapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Female patients aged 18 to 75 years with stage IV and measurable MBC were enrolled and randomly assigned to either gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1) or FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1). Both regimens were administered every 21 days for a maximum of eight cycles. RESULTS: Between October 1999 and November 2002, 259 patients (GET, n = 124; FEC, n = 135) were enrolled. Baseline characteristics were well balanced across treatment arms. After a median of 20.4 months of follow-up, median TtPD was 9.1 months and 9.0 months in the GET and FEC arms, respectively (P = .557). The ORR was 62.3% in the GET arm (n = 114) and 51.2% in the FEC arm (n = 129; P = .093). Grade 3 and 4 toxicities, including neutropenia, thrombocytopenia, anemia, stomatitis, neurosensory toxicity, and allergy, occurred significantly more often in the GET arm. CONCLUSION: No significant differences in terms of TtPD and ORR were observed between the two treatment arms. Treatment-related toxicity was higher in the GET arm.

Adolescent↗
PubMed2004

Plant coloration undermines herbivorous insect camouflage.

The main point of our hypothesis "coloration undermines camouflage" is that many color patterns in plants undermine the camouflage of invertebrate herbivores, especially insects, thus exposing them to predation and causing them to avoid plant organs with unsuitable coloration, to the benefit of the plants. This is a common case of "the enemy of my enemy is my friend" and a visual parallel of the chemical signals that plants emit to call wasps when attacked by caterpillars. Moreover, this is also a common natural version of the well-known case of industrial melanism, which illustrates the great importance of plant-based camouflage for herbivorous insects and can serve as an independent test for our hypothesis. We claim that the enormous variations in coloration of leaves, petioles and stems as well as of flowers and fruits undermine the camouflage of invertebrate herbivores, especially insects. We assume that the same principle might operate in certain animal-parasite interactions. Our hypothesis, however, does not contrast or exclude other previous or future explanations of specific types of plant coloration. Traits such as coloration that have more than one type of benefit may be selected for by several agents and evolve more rapidly than ones with a single type of advantage.

Animals↗
PubMed2004

Evaluation of CaDet, a computer-based clinical decision support system for early cancer detection: a comparison with the performance of clinicians.

Based on an analysis of the epidemiologic and clinical attributes of individual patients, the CaDet computer program presents physicians with data patterns that may require clinical attention with regard to early cancer detection. This study evaluated the performance of the program as a possible tool to aid clinicians in the latter. Patient data were obtained by a questionnaire from 160 healthy volunteers. Scored cancer alerts generated by the computer program in response to this data were evaluated in comparison to similar alerts provided by five expert internists who reviewed the same information in blinded fashion. The alert profiles generated by the computer for each of the patients examined were highly correlated to those provided by the clinicians. The computer's alert rate increased with the number of physicians who raised corresponding alerts (20%, 32%, 54%, 73% and 91%, respectively, for 1, 2, 3, 4 and 5 physicians, p < 0.0001) and with the overall weight assigned by the physicians to these alerts (22%, 56%, 84% and 90% for cumulative scores of 1-4, 5-8, 9-12 and 13 or more points, respectively, p < 0.0001). It is concluded that the CaDet computer program may have a role in improving early detection, pending the results of further clinical research.

Decision Support Systems, Clinical↗
PubMed2004

Phase II study of weekly topotecan in patients with recurrent or persistent epithelial ovarian cancer.

OBJECTIVE: To assess the toxicity and effectiveness of once-weekly administration of topotecan (Hycamtin; GlaxoSmithKline) for relapsed ovarian and primary peritoneal cancer. METHODS: Twenty-three patients with recurrent or persistent epithelial ovarian cancer (EOC) and primary peritoneal carcinoma (PPC) previously exposed to at least one line of platinum-based chemotherapy were treated with IV weekly topotecan as a 30-min bolus at a starting dose of 4 mg/m(2) administered weekly for 3 weeks in a 28-day cycle. RESULTS: The patients' median age was 62 years (42-83). Thirteen women (56.5%) were defined as having platinum-sensitive and 10 (43.5%) as having platinum-resistant disease. Altogether, 88 cycles were administered for a total of 264 weekly treatments, with a median of four courses (range 2-6). There were no treatment delays. The main bone marrow toxicity was grade II and III thrombocytopenia, necessitating dose reduction in four patients (17.4%) and treatment cessation in one patient. The most frequent nonhematologic toxicity was fatigue (nine patients, 39.1%). There were four complete responses (17.4%, three in the platinum-sensitive and one in the platinum-resistant patients) and seven (30.4%) partial responses, for an overall response rate of 47.8%. The ORR was similar in platinum-sensitive and platinum-resistant patients (47.8% and 52.2%, respectively). The median progression-free survival was 4.9 months with a mean survival time of 11.59 months. Two women sustained complete response lasting >6 months. CONCLUSION: Topotecan given as a weekly bolus is a highly active and well-tolerated treatment regimen for relapsed ovarian and primary peritoneal cancer and thus deserves further evaluation.

Adult↗
PubMed2004

Hyperthermia combined with radiation therapy in the treatment of local recurrent breast cancer.

BACKGROUND: Hyperthermia combined with radiation therapy was shown to be more effective in local recurrent breast cancer than radiotherapy alone, but its use is limited due to technical difficulties, stringent reimbursement policies and because it is time consuming. OBJECTIVES: To report our experience with a simple and convenient XRT + HT delivery system. METHODS: XRT was delivered through either electron or photon beams (total dose 30-40 Gy in previously irradiated fields or 50-70 Gy in non-irradiated fields). Hyperthermia was delivered by a dedicated HT device operating at 915 MHz. The heating session lasted 45 minutes. The maximal tumor surface temperature was set at 45 degrees C and modified according to patient comfort. No intratumoral (invasive) thermometry was used. At least two HT sessions were scheduled to each HT field during the entire XRT treatment period. Tumor response was evaluated every 3 months after completion of treatment. The overall survival was measured from XRT + HT initiation until the last follow-up. RESULTS: Fifteen women underwent 114 HT treatments delivered through 28 HT fields. Twenty-four HT fields (15 patients) were previously irradiated. There was complete infield response in 10 fields (6 patients), partial response in 8 fields (4 patients), no response or progressive disease in 4 fields (3 patients), and no parameters in 6 fields (5 patients). Eighteen fields (64%) had complete or partial response. Seven patients had outfield recurrence despite wide XRT + HT fields. Ulceration was the only major side effect (three patients, three fields). CONCLUSIONS: The combined HT+XRT delivery system, with no invasive thermometry, is a simple and effective method for treating local recurrent breast cancer.

Breast Neoplasms↗
PubMed2004

[Hormone replacement therapy in breast cancer survivors: the Israeli Society for Clinical Oncology and Radiotherapy policy letter].

The Israeli Society for Clinical Oncology and Radiotherapy appointed experts in breast cancer therapy to assess the Society's policy regarding hormone replacement therapy (HRT) in breast cancer survivors with menopausal symptoms. The first policy letter was published in November 2002, and referred to available literature at that time which included retrospective data alone. The professional literature suggested no increased risk in breast cancer recurrence or cancer specific mortality, and no effect on overall survival with the use of HRT for a limited period (up to 3 years). This data served as the rationale for international prospective studies. Former committee recommendations and precautions are detailed in the original publication. In February 2004, the interim analysis of a prospective trial, the HABIT (Hormonal replacement therapy after breast cancer--is it safe?) was published. In that trial, breast cancer survivors with menopausal symptoms were randomized to HRT (estrogens with or without progestins) or no therapy for 2 years. A total of 434 women were recruited from centers in Scandinavia who participated with the International Breast Cancer and the European Organization for Research and Treatment groups. Analysis was restricted to 345 women with at least one follow up report; median follow-up period was 2.1 years. The relative risk for breast cancer event was 3.5 (95% C.I. 1.5-8.1) in HRT users as compared with the non-HRT group and the HABIT trial was terminated. Study limitations are discussed. Thereby, at this time HRT can no longer be considered safe in breast cancer survivors. Physicians treating breast cancer survivors for severe menopausal symptoms should present study results and alternative non-hormonal treatment options to allow patients optimized consented treatment decisions.

Breast Neoplasms↗
PubMed2003

Comparison between two iodine-125 brachytherapy implant techniques: pre-planning and intra-operative by various dosimetry quality indicators.

PURPOSE: To prospectively compare two widely used seed implant techniques: pre-planning and intra-operative planning, based on 1 month post-implant CT-based evaluation. METHODS: We report results of a detailed 1 month post-operative dosimetric evaluation and comparison between 142 consecutive men with prostate adenocarcinoma treated by the pre-planning methodology and 214 men treated with the real-time, intra-operative seed implant method. RESULTS: Baseline parameters patient's age, Gleason score, clinical stage, and gland volume were similar in both groups (p>0.05). Length of physicist time and operating room team time were more than double in the pre-planned group compared to the intra-operative one (205 vs 100 min). Based on day 30 post-implant CT, for patients treated with the pre-planning method, mean V90, V100 and V150 (percent prostate volume receiving 90, 100 and 150% of the prescribed dose) were 67.5, 58.35 and 21.5%, respectively, while for the intra-operative group they were 97.9, 95.2 and 45%, respectively (p<0.01). Mean D90, expressed as percent of target matched peripheral dose (minimal dose covering 90% of the gland volume) was 53% for the pre-planned group and 114% for the intra-operative group of men (p<0.01). Short-term morbidity was minimal in both groups and did not correlate with the technique employed. CONCLUSIONS: This large-scale comparison of implant adequacy favours real-time intra-operative method. While all dosimetric parameters are significantly better with this method, no increased early morbidity was noted. Longer-term PSA-based clinical outcome should substantiate our contention of the superiority of the intra-operative method when compared to the pre-planning one.

Adenocarcinoma↗
PubMed2003

Gestation-related malignant musculoskeletal tumors.

BACKGROUND: The incidence of malignant musculoskeletal tumors during pregnancy is very low. The paucity of data precludes the drawing of solid conclusions regarding a standard approach. OBJECTIVES: To summarize our experience treating 13 pregnant women with malignant soft tissue or bone tumors. METHODS: We conducted a retrospective analysis of 13 cases of patients with either soft tissue or bone sarcoma that developed or progressed during pregnancy or immediately after delivery. RESULTS: The clinical presentation of the tumors was a growing mass and/or increasing pain and disability. Most of the masses were located in the lower part of the body and were of considerable size. Treatment given during gestation was limited to wide excision of the mass in the 28th week of gestation in one patient. All the patients reported disease progression during gestation. Vaginal delivery was possible in eight patients with no complications, cesarean section was carried out in three women, spontaneous miscarriage occurred in one and termination of pregnancy was performed in one patient. CONCLUSIONS: The diagnostic and therapeutic approaches should be tailored specifically in every pregnant woman in whom sarcoma is suspected.

Adult↗