Shmuel Argov

Ben-Gurion University of the Negev, Be'er Sheva`, Southern District, Israel

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Publications (46)90.72 Total impact

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    ABSTRACT: Cancer diagnosis using infrared spectroscopy uses absorbance of nucleic acids, carbohydrates and phosphates as biomarkers. The present work deciphers the mutual intereference in absorbance of these compnents using colonic tissues as a model.
    Fourier Transform Spectroscopy; 06/2013
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    ABSTRACT: To examine the rates of contamination of contact lens storage cases of refractive surgery candidates and compare the growth yields of the traditional method of culturing and a broth-based method. Thirty contact lens storage cases of 16 asymptomatic refractive surgery candidates were studied. Samples from the lens storage case fluid were inoculated into Bactec Peds Plus F broth (Becton Dickinson) and also directly onto blood agar, chocolate agar, and Sabouraud dextrose agar ("traditional method"). Another sample was processed for amoebal contamination. The rate of contamination of cases and the types of pathogens were evaluated for the broth-based and traditional culturing methods. Correlation between right and left storage cases of the same patient was defined as contamination of the two compartments with the same pathogen or pathogens. To avoid statistical bias, only one compartment was included in the study for these patients. Four storage cases were omitted due to growth correlation between right and left storage cases. Of the remaining 26 storage cases, 16 (61.5%) were found to be contaminated using the broth-based method and 10 (38.5%) using the traditional method (P=.011). High contamination rates were observed regardless of the type of disinfecting solution or type of contact lens used. The broth-based method had significantly greater culture yield than the traditional method. The high rates of contamination of contact lens storage cases of refractive surgery patients may put this cohort at greater risk than non-contact lens wearing candidates for developing postoperative infections.
    Journal of refractive surgery (Thorofare, N.J.: 1995) 05/2011; 27(11):811-7. DOI:10.3928/1081597X-20110505-01 · 2.78 Impact Factor
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    ABSTRACT: One of the major public health hazards is colon cancer. There is a great necessity to develop new methods for early detection of cancer. If colon cancer is detected and treated early, cure rate of more than 90% can be achieved. In this study we used FTIR microscopy (MSP), which has shown a good potential in the last 20 years in the fields of medical diagnostic and early detection of abnormal tissues. Large database of FTIR microscopic spectra was acquired from 230 human colonic biopsies. Five different subgroups were included in our database, normal and cancer tissues as well as three stages of benign colonic polyps, namely, mild, moderate and severe polyps which are precursors of carcinoma. In this study we applied advanced mathematical and statistical techniques including principal component analysis (PCA) and linear discriminant analysis (LDA), on human colonic FTIR spectra in order to differentiate among the mentioned subgroups' tissues. Good classification accuracy between normal, polyps and cancer groups was achieved with approximately 85% success rate. Our results showed that there is a great potential of developing FTIR-micro spectroscopy as a simple, reagent-free viable tool for early detection of colon cancer in particular the early stages of premalignancy among the benign colonic polyps.
    Proceedings of SPIE - The International Society for Optical Engineering 04/2010; DOI:10.1117/12.856279 · 0.20 Impact Factor
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    ABSTRACT: Colon cancer is a major public health problem due to its high disease rate and death toll worldwide. The use of FTIR microscopy in the field of cancer diagnosis has become attractive over the past 20 years. In the present study, the authors investigated the potential of FTIR microscopy to define spectral changes among normal, polyp, and cancer human colonic biopsied tissues. A large database of FTIR microscopic spectra was compiled from 230 human colonic biopsies. The database was divided into five subgroups: Normal, cancerous tissues, and three stages of benign colonic polyps, namely, mild, moderate, and severe polyps, which are precursors of carcinoma. All biopsied tissue sections were classified concurrently by an expert pathologist. The authors applied the principal components analysis (PCA) model to reduce the dimension of the original data size to 13 principal components. While PCA analysis shows only partial success in distinguishing among cancer, polyp, and the normal tissues, multivariate analysis (e.g., LDA) shows a promising distinction even within the polyp subgroups. Good classification accuracy among normal, polyp, and cancer groups was achieved with a success rate of approximately 85%. These results strongly support the potential of developing FTIR microscopy as a simple, reagent-free tool for early detection of colon cancer and, in particular, for discriminating among the benign premalignant colonic polyps having increasing degrees of dysplasia severity (mild, moderate, and severe).
    Medical Physics 03/2010; 37(3):1047-55. DOI:10.1118/1.3298013 · 3.01 Impact Factor
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    ABSTRACT: This study aimed to determine the potential of IR-spectroscopy to diagnose abnormality in histologically normal resection margins for predicting relapse in colon cancer patients. The present study evaluates potential abnormal crypt proliferation in histologically normal resection margins. Resection margins of 10 colon cancer patients (adenocarcinoma) (27 biopsies in all), found completely normal by standard histology were re-evaluated. Fourier transform infrared microscopy (FTIR-MSP) was performed on the longitudinal sections of the crypt, and spectral data collected from the base, middle and top portion of crypts. Absorbance in the region 900-1185 cm(-1) arising from carbohydrates and nucleic acids was found to be the most effective variate for such evaluation. In total 225 crypts were classified after assessing the levels of abnormality observed by the above technique. The abnormal biopsies detected using the above optical method was correlated with a relapse in the patient's history. Patients who had a relapse had at least one abnormal biopsy (crypt) based on the present methodology. Among the patients, the only case without a relapse was also the case where no abnormal crypts were found in any biopsies from the resection margins. The agreement between the biopsy status, as determined by the optical methodology, and the relapse of colonic malignancy based on the patients' medical files, establishes the translational nature of FTIR-MSP for medical purposes and hints at future clinical evaluation of the biopsies using this technique to determine more precisely the zone of excision during anastomosis.
    The Analyst 03/2010; 135(3):538-44. DOI:10.1039/b920926n · 3.91 Impact Factor
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    ABSTRACT: We present the clinicopathologic features and treatment plans of 328 consecutive stage I (T1N0M0) breast cancer patients seen at a regional medical center in Israel. Predicted 10-year mortality risk was calculated using the Adjuvant! Online website. The 21-gene recurrence score (RS) (OncotypeDx) was obtained on a minority of patients. Eighty-nine per cent of patients had estrogen receptor (ER) and/or progesterone receptor (PgR) positive tumors. In 43.3% of patients history of an invasive malignancy was reported in a first degree relative and in 15.5% specifically breast and/or ovarian cancer was reported. Chemotherapy was added to endocrine therapy in 59 ER/PgR positive patients, decreasing predicted 10-year mortality risk by a median of 1.8%. Individualized risk estimation by genetic analysis may further decrease the use of chemotherapy in stage I patients. Breast cancer screening may provide an opportunity to identify cancer prone families.
    Breast (Edinburgh, Scotland) 10/2009; 18(5):316-21. DOI:10.1016/j.breast.2009.08.004 · 2.58 Impact Factor
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    ABSTRACT: Idiopathic sclerosing pseudotumor of the orbit is a unique clinico-pathologic entity, similar to retroperitoneal fibrosis, that is characterized by primary, chronic and immunologically mediated fibrosis, poor response to corticosteroid treatment or radiotherapy and frequent visual disability. The clinical and pathologic findings of our case are reviewed.
    Orbit 07/2009; 13(4):199-202. DOI:10.3109/01676839409107927
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    ABSTRACT: Fourier transform infrared microspectroscopy (FTIR-MSP) is an analytical method with a promising potential for detecting the spectral changes due to cancerous changes in cells. The purpose of the present study is monitoring biochemical spectral changes accompanying viral cancer progression in cells and tissues using FTIR-MSP. As a model system, we used cells in culture which were transformed to malignant cells by infection with murine sarcoma virus (MuSV) and cervical tissues at different neoplastic stages. In order to devise a systematic follow-up of the cancer progression, it was essential first to determine and validate consistent and significant spectral biomarkers, which can evidently discriminate between normal and cancerous cells/tissues. Then these biomarkers were used for the characterization and classification of early stages of malignant transformation utilizing discriminant classification function techniques. Our study points out that malignancy progression can be eminently graded for both cell lines and tissues. For example, using the array of four biomarkers: A(2958)A(2852)+A(2923),A(1121)/A(1015),A(1171)/A(1152)and|A(1082)-A(1056)|A(1028), we attained that the classification accuracies of different premalignant stages of cell lines and tissues were varied between 89.5 and 97.4%. These results strongly support the potential of developing FTIR microspectroscopy as a simple, reagent free method for early detection and accurate differentiation of premalignant stages.
    Biochimica et Biophysica Acta 10/2008; 1780(9):1038-46. DOI:10.1016/j.bbagen.2008.05.008 · 4.66 Impact Factor
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    ABSTRACT: Infrared spectroscopy is widely perceived as a future technology for cancer detection and grading. Malignant melanoma, an aggressive skin cancer, is accessible to non-invasive IR radiation based surface probes for its identification and grading. The present work examines the differences in the IR spectra of melanoma tissues and the surrounding epidermis in skin biopsies with the objective of identifying diagnostic parameters and suitable computational/statistical methods of analysis. Melanoma could be differentiated from the epidermis in biopsies of 55 patients, using parameters derived from absorbance bands originating from molecular vibrations of nucleic acids and/or their bases. Additionally, absorbances from tyrosine and phosphate that are abnormally elevated in malignant melanoma could be used as markers. Two-dimensional plots of these parameters in tandem with advanced statistical methods successfully demonstrate the potential of IR spectroscopy to distinguish between epidermal and melanoma regions with a high classification success. The work underlines the importance of developing data analysis methods in FTIR based diagnosis using melanoma as a model system.
    The Analyst 04/2008; 133(3):372-8. DOI:10.1039/b712040k · 3.91 Impact Factor
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    ABSTRACT: The present study focuses on evaluating the potential of flattened AgClBr fibre-optic evanescent wave spectroscopy (FTIR-FEWS) technique for detection and identification of cancer cells in vitro using cell culture as a model system. The FTIR-FEWS results are compared to those from FTIR-microspectroscopy (FTIR-MSP) method extensively used to identify spectral properties of intact cells. Ten different samples of control and malignant cells were measured in parallel by the above two methods. Our results show a significant similarity between the results obtained by the two methodologies. The absorbance level of Amide I/Amide II, phosphates and carbohydrates were significantly altered in malignant compared to the normal cells using both systems. Thus, common biomarkers such as Amide I/Amide II, phosphate and carbohydrate levels can be derived to discern between normal and cancer cells. However, marked differences are also noted between the two methodologies in the protein bands due to CH3 bending vibration (1480-1350 cm(-1)). The spectral differences may be attributed to the variation in the penetration depth of the two methodologies. The use of flattened fibre rather than the standard cylindrical fibre has several practical advantages and is considered as an important step towards in vivo measurements in real time, such as that of skin nevi and melanoma using special designs of fibre-optic-based sensors.
    Journal of Microscopy 12/2007; 228(Pt 2):200-10. DOI:10.1111/j.1365-2818.2007.01840.x · 2.15 Impact Factor
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    ABSTRACT: Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarcinoma specimens (N=28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N=30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P=0.004) or hyperplastic specimens (P=0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P=0.041 and P=0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean=0.7; median=0; range=0-5) than in adjacent tissue (mean=2.5; median=1; range=0-15; P=.021) and hyperplasia (mean=1.9; median=2; range=0-5; P=.006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean=8.6; median=7.5; range=30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P=0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean=12; median=10; range=30; P=0.01) and clustered (P=0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P=0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue.
    British Journal of Cancer 04/2007; 96(6):980-5. DOI:10.1038/sj.bjc.6603650 · 4.82 Impact Factor
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    ABSTRACT: Constitutive expression of cell-associated, but not secreted, interleukin-1alpha (IL-1alpha) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1alpha-expressing tumor cells induce progressive tumors in mice. In vivo and ex vivo experiments have shown that regression of IL-1alpha-positive fibrosarcoma cells depends on CD8(+) T cells, which can also be activated in CD4(+) T cell-depleted mice, with some contribution of natural killer cells. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, some early and transient manifestations of antitumor-specific immunity, such as activation of specific proliferating T cells, are evident; however, no development of cytolytic T lymphocytes or other antitumor protective cells could be detected. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, the development of early tumor-mediated suppression was observed, and in spleens of mice injected with IL-1alpha-positive fibrosarcoma cells, protective immunity developed in parallel to tumor regression. Treatment of mice bearing violent fibrosarcoma tumors with syngeneic-inactivated, IL-1alpha-positive fibrosarcoma cells, at a critical interval after injection of the malignant cells (Days 5-12), induced tumor regression, possibly by potentiating and amplifying transient antitumor cell immune responses or by ablation of tumor-mediated suppression. Membrane-associated IL-1alpha may thus serve as an adhesion molecule, which allows efficient cell-to-cell interactions between the malignant and immune effector cells that bear IL-1Rs and function as a focused cytokine with adjuvant activities at nontoxic, low levels of expression. Our results also point to the potential of using antitumor immunotherapeutic approaches using cell-associated IL-1alpha.
    Journal of Leukocyte Biology 08/2006; 80(1):96-106. DOI:10.1189/jlb.0905509 · 4.30 Impact Factor
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    ABSTRACT: Fourier-transform infrared spectroscopy has shown alterations of spectral characteristics of cells and tissues as a result of carcinogenesis. The research reported here focuses on the diagnosis of cancer in formalin-fixed biopsied tissue for which immunochemistry is not possible and when PAP-smear results are to be confirmed. The data from two groups of patients (a control group and a group of patients diagnosed with cervical cancer) were analyzed. It was found that the glucose/phosphate ratio decreases (by 23-49%) and the RNA/DNA ratio increases (by 38-150%) in carcinogenic compared with normal tissue. Fourier-transform microspectroscopy was used to examine these tissues. This type of study in larger populations may help to set standards or classes with which to use treated biopsied tissue to predict the possibility of cancer. Probabilistic neural networks and statistical tests as parts of these biopsies predict the possibility of cancer with a high degree of accuracy (> 95%).
    Applied Optics 06/2005; 44(18):3725-34. DOI:10.1364/AO.44.003725 · 1.78 Impact Factor
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    ABSTRACT: Malignant melanoma, a malignant neoplasm of epidermal melanocytes is the third most common skin cancer. In many cases, melanoma develops from nevus, which is considered as the nonmalignant stage. Fourier transform infrared microspectroscopy (FTIR-MSP), which is based on characteristic molecular vibrational spectra of cells, was used to investigate spectral differences between melanoma, nevus, and the corresponding normal epidermis. In the present work, FTIR-MSP was performed on formalin-fixed biopsies of melanoma and nevi along with the adjoining histologically normal epidermis to understand the biochemical variations from the epidermis and identify suitable parameters for differentiation of nevi from melanoma. The comparative analysis of various parameters calculated from the spectral data of the normal epidermis and the abnormal regions showed that the changes in the nucleic acids was a significant indicator of the abnormal nature of the tissues. The RNA/DNA ratio was decreased in case of both melanoma and nevus compared to the epidermis. The amide II/amide I ratio was greater for nevus and melanoma compared to the epidermis. In contrast to other organs, the analysis of carbohydrates was not found as a suitable indicator in case of malignant melanoma. Shifts in band wave number were found to be a major distinguishing feature between the melanoma and compound nevi. The present study helps in the identification of spectral features suitable for distinction of melanoma from nevus that appear similar even in FTIR spectral features and thus can pave the way for development of in vivo screening systems based on these diagnostic markers.
    The Scientific World Journal 04/2005; 5:173-82. DOI:10.1100/tsw.2005.1 · 1.73 Impact Factor
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    ABSTRACT: FTIR spectroscopy has been extensively used to understand the differences between normal and malignant cells and tissues. In the present study, FTIR microspectroscopy was performed on biopsies to evaluate parameters deduced from changes in nucleic acid absorbance monitored at various characteristic wavenumbers in the Mid-IR region. The data showed that there were differences in the spectra of normal and malignant tissues from several organs such as colon, cervix, skin and blood with respect to absorbance due to nucleic acids. Similar results were observed in the case of cell lines that were transformed to induce carcinogenesis. Of the several ratios examined for consistency in differentiating cancer and normal tissues, the I(996 cm(-1))/I(966 cm(-1)) showed promise as a distinguishing parameter and was comparable to the I(1121 cm(-1))/I(1020 cm(-1)) ratio reported in many earlier studies. The absorbance of nucleic acids is presented with an emphasis on the application of FTIR microspectroscopy for diagnosis of malignancy. Our results indicate that usage of nucleic acid absorbance yield statistically significant parameters, which could differentiate normal and cancerous tissues.
    Technology in cancer research & treatment 01/2005; 3(6):629-38. DOI:10.1177/153303460400300613 · 1.89 Impact Factor
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    ABSTRACT: Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a technique for detection of abnormal cell proliferation and premalignant conditions. In the present study, we investigate the absorbance in the sensitive wavenumber region between 2800 and 3000 cm(-1), which has been known to be due to the antisymmetric and symmetric stretching vibrations of CH2 and CH3 groups of proteins and lipids. We report common biomarkers from this region that distinguish between normal and malignant tissues and cell lines. Based on our findings, we propose that the wavenumber region around 2800 to 3000 cm(-1) in the FTIR spectra of cells and tissues could provide valuable scientific evidence at the onset of premalignancy and may be used for ex vivo and in vitro detection of carcinogenesis. To further examine the utility of these markers in cancer diagnosis and management, they are tested successfully in monitoring the changes occurring in leukemia patients during chemotherapy.
    Journal of Biomedical Optics 01/2005; 10(5):054017. DOI:10.1117/1.2080368 · 2.75 Impact Factor
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    ABSTRACT: Elucidation of the evolution of inflammatory bowel disease (IBD) to cancer by clinical symptoms and histopathology of biopsies is important. Fourier transform infrared microspectroscopy (FTIR-MSP) has shown promise as a diagnostic tool for distinction of normal and cancer cells and tissues. In the present work, FTIR-MSP is used to evaluate IBD cases and to study the IR spectral characteristic with respect to cancer and normal tissues from formalin-fixed colonic biopsies from patients. Specific regions of the spectra were analyzed by statistical tools to study variations in metabolites that signified changes between the two pathological conditions: IBD and cancer. IBD tissues can be grouped with cancer or normal tissue using certain parameters such as phosphate content and RNA/DNA ratio as calculated from the spectra and show intermediate levels with regard to these metabolites. Further classification of the spectra by cluster analysis indicated which cases of Crohn's disease (3 of 10 cases) or ulcerative colitis (7 of 10 cases) were more likely to progress to cancer. The study exhibits that FTIR-MSP can detect gross biochemical changes in morphologically identical IBD and cancer tissues and suggest which cases of IBD may require further evaluation for carcinogenesis.
    Biopolymers 12/2004; 75(5):384-92. DOI:10.1002/bip.20154 · 2.29 Impact Factor
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    ABSTRACT: Detection of malignancy at early stages is crucial in cancer prevention and management. Fourier transform infrared (FTIR) spectroscopy has shown promise as a non-invasive method with diagnostic potential in cancer detection. Studies were conducted with formalin-fixed biopsies of melanoma and cervical cancer by FTIR microspectroscopy (FTIR-MSP) to detect common biomarkers, which occurred in both types of cancer distinguishing them from the respective non-malignant tissues. Both types of cancer are diagnosed on skin surfaces. The spectra were analysed for changes in levels of biomolecules such as RNA, DNA, phosphates and carbohydrate (glycogen). Whereas carbohydrate levels showed a good diagnostic potential for detection of cervical cancer, this was not the case for melanoma. However, variation of the RNA/DNA ratio as measured at I(1121)/I(1020) showed similar trends between non-malignant and malignant tissues in both types of cancer. The ratio was higher for malignant tissues in both types of cancer.
    Journal of Microscopy 08/2004; 215(Pt 1):86-91. DOI:10.1111/j.0022-2720.2004.01356.x · 2.15 Impact Factor
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    ABSTRACT: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. In the present work, feasibility studies of FTIR-MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR-MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal-looking crypts, especially from those biopsies that are taken from sites far away from cancer. This method could give rise to a reduction in false-negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.
    Scandinavian Journal of Gastroenterology 07/2004; 39(6):557-66. DOI:10.1080/00365520410004695 · 2.33 Impact Factor
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    ABSTRACT: Recently, Fourier transform infrared (FTIR)-spectroscopy has been used to monitor cell growth by several works. Conventionally, the study of cell and tissue dynamics at molecular levels is carried out through various approaches like histochemical methods, application of molecular biology and immunology. Colonic crypts display a pattern in cell growth along their height. Histologically normal sections obtained from formalin fixed biopsies of colon cancer patients were studied in the present work through vibrational spectroscopy. The evolution and development of the normal human colonic crypts manifested in Fourier transform infrared-microspectroscopy (FTIR-MSP) as spectral changes in the levels of nucleic acids, proteins, carbohydrates and lipids. The results indicate that the level of carbohydrates, nucleic acids and lipids increases only till the middle of the crypt up to which the maturation zone is restricted and thereafter decreases till the top where the cells are exfoliated. These observations are in coherence with earlier reports on crypt proliferation. We identify the normal pattern of various biochemicals along the colonic crypt based on data analyzed from FTIR-MSP. This study affords an important example of the application of microscopic vibrational spectroscopy for understanding basic cell processes from formalin fixed tissues where in vivo studies and immunological methods are not feasible.
    Vibrational Spectroscopy 03/2004; 34(2):301-308. DOI:10.1016/j.vibspec.2004.01.009 · 1.55 Impact Factor

Publication Stats

765 Citations
90.72 Total Impact Points

Institutions

  • 1989–2011
    • Ben-Gurion University of the Negev
      • • Faculty of Health Sciences
      • • Department of Morphology
      • • Department of Physics
      • • Department of Pathology
      Be'er Sheva`, Southern District, Israel
  • 1987–2010
    • Soroka Medical Center
      • • Department of Pathology
      • • Department of Medicine
      Be'er Sheva`, Southern District, Israel
  • 1988
    • Tel Aviv University
      • Faculty of Life Sciences
      Tell Afif, Tel Aviv, Israel