Craig Allred - Academia.edu (original) (raw)

Papers by Craig Allred

Research paper thumbnail of Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102

Journal of Clinical Oncology, 2005

Purpose We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versu... more Purpose We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status. Patients and Methods Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated. Results Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in ...

Research paper thumbnail of Fixation Time Does Not Affect Expression of HER2/neu: A Pilot Study

American Journal of Clinical Pathology, 2010

Research paper thumbnail of Testing for erbB-2 by Immunohistochemistry in Breast Cancer

American Journal of Clinical Pathology, 2000

Research paper thumbnail of Whole-genome analysis informs breast cancer response to aromatase inhibition

Research paper thumbnail of HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients

Breast cancer research and treatment, Jul 1, 2016

HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohisto... more HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis. Consecutive 280 invasive breast cancer were examined. Statuses of HER2 protein and gene were evaluated in whole tumor sections of HER2 GPA slides. HER2 protein and gene combination patterns were classified to six phenotypic and genotypic types for each case, as well as at individual cell levels: (A) IHC and DISH positive; (B) IHC positive and DISH negative; (C) IHC equivocal and DISH positive; (D) IHC equivocal and DISH negative; (E) IHC negative and DISH positive; and (F) IHC and DISH negative. The presence of HER2-heterogeneity was determined by the existence of at least t...

Research paper thumbnail of Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic …

Breast cancer research …, 2001

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical s... more Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis.

Research paper thumbnail of Abstract P2-04-06: Demonstration of immune cell and pathway heterogeneity in Singapore DCIS samples using novel hyperplexing method (MultiOmyx®)

Research paper thumbnail of Effect of chemoattractants on chemiluminescence

Infection and immunity, 1978

Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence th... more Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments reported here, the influence of three chemoattractants and three chemotactic modulators upon the chemiluminescence induced by opsonized zymosan was studied. The chemoattractants investigated (including bacterial factor derived from Escherichia coli, the simple peptide formylmethionylalanine, and activated human complement), which initiate directed movement when presented to cells in a concentration gradient, significantly enhanced zymosan-induced chemiluminescence. In the absence of opsonized zymosan, however, they had no effect on the chemiluminescence response. In contrast, the chemotactic modulators studied (including carbamylcholine, phenylephrine, and cyclic guanosine 5'-monophosphate, which are not chemotactic by themselves but can enhance or depress the movement of polymorphonuclear leukocytes initiated b...

Research paper thumbnail of Supplemental Data Regulation of In Situ to Invasive Breast Carcinoma Transition

and D-MYOEP-7). Tags were further filtered to have a maximum count from all libraries above 10 pe... more and D-MYOEP-7). Tags were further filtered to have a maximum count from all libraries above 10 per 50,000 and to have a >1.5 fold difference between ITGB6 and MUC1 libraries. Filtered data were log transformed and clustered (hierarchical, complete linkage) using the Cluster and TreeView software (Eisen et al., 1998). Color settings were adjusted to set tag count 4 per 50,000 as black. Tag counts below 4 were green and above 4 were red. Gene ontology enrichment scores for the SAGE libraries were calculated as-log(p-value) by comparing the significantly highly expressed genes in each cell type (ITGB6+ and MUC1+, or Myoep and Epi) analyzed to the background (all genes in the ITGB6+/MUC1+ libraries, or for human breast libraries, all genes with tag count >=10 per 100K in at least one library) with one-sided Fisher test. Selection of gene list for Table 1 Genes were selected based on the following criteria: (1) statistically significant (p<0.05) difference between ITGB6+ and MUC1+ libraries; (2) statistically significant (p<0.05) difference between human MYOEP and EPI groups based on t-test or Wilcox test (for genes high in ITGB6+ and MYOEP or MUC1+ and EPI), or ratio of DMYOEP/NMYOEP > 10-fold (for genes high in ITGB6+ and DMYOEP); (3) ratio of ITGB6+/MUC1+ and MYOEP/EPI are in the same direction; (4) ratio of both ITGB6+/MUC1+ and MYOEP/EPI are > 2-fold; and (5) tag count >10 per 100k in at least one of the primary human tissue libraries. FISH analysis For MYC FISH LSI C-MYC (Spectrum Orange), LSI MYC Dual Color Break Apart Probe (5' Spectrum Orange, 3' Spectrum Green), CEP8 (Spectrum Aqua and Spectrum Green), and CEP10 (Spectrum Aqua) probes were purchased from Vysis, Inc. (Downers Grove, IL). Cells were treated with colcemid, harvested, and used for metaphase chromosome spreads preparations according to standard protocols. Hybridization of metaphase chromosomes was performed as previously described (Ney et al., 1993). Slides were examined using a fluorescence microscope equipped with a CytoVysion capturing system (Applied Imaging Corp., San Jose, CA). Immuno-FISH (iFISH) using formalin fixed paraffin embedded tissue The procedure is a modification of a protocol provided by Peters et al. (Peters et al., 2005). I. Deparaffinization and Pretreatment Reagents: EZ-DeWax: Biogenex #HK585-5K 20x Citrate buffer pH 6.0: Zymed Labs #00-5000 Human Cot-1 DNA: Invitrogen # 15279-011 (predominantly 50 to 300 bp in size and enriched for repetitive DNA sequences) Mouse Cot-1 DNA: Invitrogen # 18440-016 (predominantly 50 to 300 bp in size and enriched for repetitive DNA sequences)

Research paper thumbnail of Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in Carcinoma

Cell, 2008

Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting unco... more Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting uncontrolled proliferation. The role polarity proteins play during tumorigenesis in mammals is poorly understood. We demonstrate that knockdown of Scribble in mammary epithelia disrupts cell polarity, blocks three-dimensional morphogenesis, inhibits apoptosis and induces dysplasia in vivo that progress to tumors after long latency. Knockdown of Scribble also cooperates with oncogenes such as Myc to transform epithelial cells in 3D acini and induce tumors in vivo by blocking activation of an apoptosis pathway. Like knockdown, mislocalization of Scribble from cell-cell junction was sufficient to promote cell transformation. Interestingly, spontaneous mammary tumors in mice and humans possess both downregulated and mislocalized Scribble suggesting a selection-pressure for Scribble inactivation. Thus, we demonstrate that Scribble is a novel regulator of breast cancer and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.

Research paper thumbnail of Influence of Phenylbutazone on Leukocyte Chemiluminescence and Function

Acta Pathologica Microbiologica Scandinavica Section C Immunology, 2009

The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular... more The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular killing of bacteria has been examined. A marked reduction of chemiluminescence and intracellular killing of bacteria was observed. The effect on phagocytosis was less pronounced. High drug concentrations nearly abolished light emission, and concentrations equivalent to those obtained in plasma during therapy caused a 25--30% reduction. The effect occurred within less than 10 minutes. No permanent effect upon resting cells was observed. Phenylbutazone reduced the effect of sodium azide on leukocyte chemiluminescnece, indicating that the drug might also inhibit myeloperoxidase dependent chemiluminescnece. Whether these impairments of leukocyte function also take place in vivo resulting in enhanced susceptibility to infection remains unknown.

Research paper thumbnail of Methods and compositions in breast cancer diagnosis and therapeutics

Research paper thumbnail of p53 Is Mutated in a Subset of Advanced-Stage Prostate Cancers

Cancer Research, Jul 15, 1993

Inactivation ofp53, a tumor suppressor gene, contributes to the genesis and/or progression of a s... more Inactivation ofp53, a tumor suppressor gene, contributes to the genesis and/or progression of a substantial fraction of all human cancers, includ ing-SO'V of breast, lung, and colon carcinomas. Mutated p53 alÃ-eles typically contain missense single-base substitutions within exons 5-8 and encode abnormally stable p53 proteins that accumulate to high levels in tumor cell nuclei. To evaluate the frequency, type, and clinical significance of p53 mutation in human prostate cancer, archival tumor material from 150 prostate cancer patients was examined by immunohistochemistry (IHC) with anti-p53 antibodies. Abnormal nuclear p53 accumulation (IHC) was observed in 19 tumors (12.7%) and was strongly related to disease stage (23% of 69 stage III or IV tumors were IHC* versus 4% of 74 stage O-II tumors; P < 0.001, Fisher's exact test). The methods of polymerase chain reaction, single-strand conformational polymorphism, and direct sequencing were used to identify mutations, predominantly missense single-base substitutions in exons 5, 7, or 8 in 9 of 14 IHC* cases but in none of 20 IHC~cases; 5 of these mutations were G:C-»A:T transitions at CpG dinucleotides. These data indicate that mutated p53 alÃ-elesare quite uncommon in early prostate cancers but are found in 20-25% of advanced cancers, suggesting a role for p53 mutation in the progression of at least a subset of prostate cancers.

Research paper thumbnail of The assessment of HER2 status in breast cancer: the past, the present, and the future

Pathology International, 2016

Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved... more Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semiquantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.

Research paper thumbnail of Comment on: The influence of menstrual cycle phase on surgical treatment of primary breast cancer: Have we made any progress over the past 13 years? Author's reply

Journal of the National Cancer Institute, 2002

Research paper thumbnail of Method of quantitative immunohistochemistry and in situ hybridization

Research paper thumbnail of Suppression of interleukin 2 production by sera obtained from hypersensitivity granuloma-bearing mice with defective T cell-mediated immune responses

Immunobiology, Feb 28, 1989

Hypersensitivity pulmonary granulomas were able to induce by the intratracheal injection of antig... more Hypersensitivity pulmonary granulomas were able to induce by the intratracheal injection of antigen-conjugated Sepharose 4B beads into immunized mice. The mice with hypersensitivity granulomas showed a lack of T cell-mediated immune responses to antigens both in vivo (delayed type footpad reaction) and in vitro (lymph node cell proliferation) in association with impaired interleukin 2 (IL 2) production by suppressor cells in lymph nodes. However, no immunosuppressive factors were detected in the granuloma lesions. In the present study, we describe that the sera obtained from these mice contain suppressive factor(s) capable of inhibiting IL 2 production by immune lymph node cells. The appearance of serum suppressor factor(s) is correlated well with inhibition of delayed hypersensitivity in such mice. Partial characterization of suppressor factor(s) showed it is absorbed by T cells and may be proteins. The approximate molecular weight of the factor ranged from 12 to 67 kd. These results suggest that the suppressive mechanisms such as the suppressor cells and serum inhibitory factor(s) may be responsible for the impaired IL 2 production and, therefore, for the lack of both in vivo and in vitro expressions of T cell-mediated immune responses to antigens in mice with hypersensitivity granulomas.

Research paper thumbnail of Compositions and Methods of Use of Het

Research paper thumbnail of Methods and compositions in breast cancer diagnosis and therapeutics

Research paper thumbnail of Improved methods of estimating mitotic activity in solid tumors

Research paper thumbnail of Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102

Journal of Clinical Oncology, 2005

Purpose We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versu... more Purpose We evaluated the efficacy of cyclophosphamide, methotrexate, and fluorouracil (CMF) versus cyclophosphamide, doxorubicin, and fluorouracil (CAF) in node-negative breast cancer patients with and without tamoxifen (TAM), overall and by hormone receptor (HR) status. Patients and Methods Node-negative patients identified by tumor size (> 2 cm), negative HR, or high S-phase fraction (n = 2,690) were randomly assigned to CMF, CAF, CMF + TAM (CMFT), or CAF + TAM (CAFT). Cox regression evaluated overall survival (OS) and disease-free survival (DFS) for CAF versus CMF and TAM versus no TAM separately. Two-sided CIs and one-sided P values for planned comparisons were calculated. Results Ten-year estimates indicated that CAF was not significantly better than CMF (P = .13) for the primary outcome of DFS (77% v 75%; HR = 1.09; 95% CI, 0.94 to 1.27). CAF had slightly better OS than CMF (85% v 82%, HR = 1.19 for CMF v CAF; 95% CI, 0.99 to 1.43); values were statistically significant in ...

Research paper thumbnail of Fixation Time Does Not Affect Expression of HER2/neu: A Pilot Study

American Journal of Clinical Pathology, 2010

Research paper thumbnail of Testing for erbB-2 by Immunohistochemistry in Breast Cancer

American Journal of Clinical Pathology, 2000

Research paper thumbnail of Whole-genome analysis informs breast cancer response to aromatase inhibition

Research paper thumbnail of HER2 intratumoral heterogeneity analyses by concurrent HER2 gene and protein assessment for the prognosis of HER2 negative invasive breast cancer patients

Breast cancer research and treatment, Jul 1, 2016

HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohisto... more HER2 gene-protein assay (GPA) is a new method for the simultaneous evaluation of HER2 immunohistochemistry (IHC) and HER2 dual in situ hybridization (DISH) on single tissue sections of breast cancer. We investigated the presence of HER2 gene and protein discrepancy and HER2-heterogeneity using HER2-GPA. HER2 status was analyzed for the correlation between the presence of HER2-heterogeneity and patient prognosis. Consecutive 280 invasive breast cancer were examined. Statuses of HER2 protein and gene were evaluated in whole tumor sections of HER2 GPA slides. HER2 protein and gene combination patterns were classified to six phenotypic and genotypic types for each case, as well as at individual cell levels: (A) IHC and DISH positive; (B) IHC positive and DISH negative; (C) IHC equivocal and DISH positive; (D) IHC equivocal and DISH negative; (E) IHC negative and DISH positive; and (F) IHC and DISH negative. The presence of HER2-heterogeneity was determined by the existence of at least t...

Research paper thumbnail of Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic …

Breast cancer research …, 2001

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical s... more Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) is highly expressed during critical stages of lung development and carcinogenesis. To determine if the expression of hnRNP-A2/B1 is an informative biomarker in breast carcinogenesis, we analyzed hnRNP-A2/B1 overexpression by immunohistochemistry in archived specimens. Expression was detected in 48/85 (56.5%) primary invasive breast cancers and 7/72 (9.7%) specimens of normal breast tissue. Northern analysis of breast cancer cells also demonstrated higher level of hnRNP-A2/B1 expression compared to normal or transformed breast cells. Expression of hnRNP-A2/B1 in breast cancer cells was decreased by exposure to retinoids coordinately with decreased cell growth. These results warrant further evaluation of hnRNP-A2/B1 as a marker of breast carcinogenesis.

Research paper thumbnail of Abstract P2-04-06: Demonstration of immune cell and pathway heterogeneity in Singapore DCIS samples using novel hyperplexing method (MultiOmyx®)

Research paper thumbnail of Effect of chemoattractants on chemiluminescence

Infection and immunity, 1978

Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence th... more Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments reported here, the influence of three chemoattractants and three chemotactic modulators upon the chemiluminescence induced by opsonized zymosan was studied. The chemoattractants investigated (including bacterial factor derived from Escherichia coli, the simple peptide formylmethionylalanine, and activated human complement), which initiate directed movement when presented to cells in a concentration gradient, significantly enhanced zymosan-induced chemiluminescence. In the absence of opsonized zymosan, however, they had no effect on the chemiluminescence response. In contrast, the chemotactic modulators studied (including carbamylcholine, phenylephrine, and cyclic guanosine 5'-monophosphate, which are not chemotactic by themselves but can enhance or depress the movement of polymorphonuclear leukocytes initiated b...

Research paper thumbnail of Supplemental Data Regulation of In Situ to Invasive Breast Carcinoma Transition

and D-MYOEP-7). Tags were further filtered to have a maximum count from all libraries above 10 pe... more and D-MYOEP-7). Tags were further filtered to have a maximum count from all libraries above 10 per 50,000 and to have a >1.5 fold difference between ITGB6 and MUC1 libraries. Filtered data were log transformed and clustered (hierarchical, complete linkage) using the Cluster and TreeView software (Eisen et al., 1998). Color settings were adjusted to set tag count 4 per 50,000 as black. Tag counts below 4 were green and above 4 were red. Gene ontology enrichment scores for the SAGE libraries were calculated as-log(p-value) by comparing the significantly highly expressed genes in each cell type (ITGB6+ and MUC1+, or Myoep and Epi) analyzed to the background (all genes in the ITGB6+/MUC1+ libraries, or for human breast libraries, all genes with tag count >=10 per 100K in at least one library) with one-sided Fisher test. Selection of gene list for Table 1 Genes were selected based on the following criteria: (1) statistically significant (p<0.05) difference between ITGB6+ and MUC1+ libraries; (2) statistically significant (p<0.05) difference between human MYOEP and EPI groups based on t-test or Wilcox test (for genes high in ITGB6+ and MYOEP or MUC1+ and EPI), or ratio of DMYOEP/NMYOEP > 10-fold (for genes high in ITGB6+ and DMYOEP); (3) ratio of ITGB6+/MUC1+ and MYOEP/EPI are in the same direction; (4) ratio of both ITGB6+/MUC1+ and MYOEP/EPI are > 2-fold; and (5) tag count >10 per 100k in at least one of the primary human tissue libraries. FISH analysis For MYC FISH LSI C-MYC (Spectrum Orange), LSI MYC Dual Color Break Apart Probe (5' Spectrum Orange, 3' Spectrum Green), CEP8 (Spectrum Aqua and Spectrum Green), and CEP10 (Spectrum Aqua) probes were purchased from Vysis, Inc. (Downers Grove, IL). Cells were treated with colcemid, harvested, and used for metaphase chromosome spreads preparations according to standard protocols. Hybridization of metaphase chromosomes was performed as previously described (Ney et al., 1993). Slides were examined using a fluorescence microscope equipped with a CytoVysion capturing system (Applied Imaging Corp., San Jose, CA). Immuno-FISH (iFISH) using formalin fixed paraffin embedded tissue The procedure is a modification of a protocol provided by Peters et al. (Peters et al., 2005). I. Deparaffinization and Pretreatment Reagents: EZ-DeWax: Biogenex #HK585-5K 20x Citrate buffer pH 6.0: Zymed Labs #00-5000 Human Cot-1 DNA: Invitrogen # 15279-011 (predominantly 50 to 300 bp in size and enriched for repetitive DNA sequences) Mouse Cot-1 DNA: Invitrogen # 18440-016 (predominantly 50 to 300 bp in size and enriched for repetitive DNA sequences)

Research paper thumbnail of Deregulation of Scribble Promotes Mammary Tumorigenesis and Reveals a Role for Cell Polarity in Carcinoma

Cell, 2008

Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting unco... more Loss of cell polarity proteins such as Scribble induces neoplasia in Drosophila by promoting uncontrolled proliferation. The role polarity proteins play during tumorigenesis in mammals is poorly understood. We demonstrate that knockdown of Scribble in mammary epithelia disrupts cell polarity, blocks three-dimensional morphogenesis, inhibits apoptosis and induces dysplasia in vivo that progress to tumors after long latency. Knockdown of Scribble also cooperates with oncogenes such as Myc to transform epithelial cells in 3D acini and induce tumors in vivo by blocking activation of an apoptosis pathway. Like knockdown, mislocalization of Scribble from cell-cell junction was sufficient to promote cell transformation. Interestingly, spontaneous mammary tumors in mice and humans possess both downregulated and mislocalized Scribble suggesting a selection-pressure for Scribble inactivation. Thus, we demonstrate that Scribble is a novel regulator of breast cancer and that deregulation of polarity pathways promotes dysplastic and neoplastic growth in mammals by disrupting morphogenesis and inhibiting cell death.

Research paper thumbnail of Influence of Phenylbutazone on Leukocyte Chemiluminescence and Function

Acta Pathologica Microbiologica Scandinavica Section C Immunology, 2009

The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular... more The effect of phenylbutazone on human leukocyte chemiluminescence, phagocytosis and intracellular killing of bacteria has been examined. A marked reduction of chemiluminescence and intracellular killing of bacteria was observed. The effect on phagocytosis was less pronounced. High drug concentrations nearly abolished light emission, and concentrations equivalent to those obtained in plasma during therapy caused a 25--30% reduction. The effect occurred within less than 10 minutes. No permanent effect upon resting cells was observed. Phenylbutazone reduced the effect of sodium azide on leukocyte chemiluminescnece, indicating that the drug might also inhibit myeloperoxidase dependent chemiluminescnece. Whether these impairments of leukocyte function also take place in vivo resulting in enhanced susceptibility to infection remains unknown.

Research paper thumbnail of Methods and compositions in breast cancer diagnosis and therapeutics

Research paper thumbnail of p53 Is Mutated in a Subset of Advanced-Stage Prostate Cancers

Cancer Research, Jul 15, 1993

Inactivation ofp53, a tumor suppressor gene, contributes to the genesis and/or progression of a s... more Inactivation ofp53, a tumor suppressor gene, contributes to the genesis and/or progression of a substantial fraction of all human cancers, includ ing-SO'V of breast, lung, and colon carcinomas. Mutated p53 alÃ-eles typically contain missense single-base substitutions within exons 5-8 and encode abnormally stable p53 proteins that accumulate to high levels in tumor cell nuclei. To evaluate the frequency, type, and clinical significance of p53 mutation in human prostate cancer, archival tumor material from 150 prostate cancer patients was examined by immunohistochemistry (IHC) with anti-p53 antibodies. Abnormal nuclear p53 accumulation (IHC) was observed in 19 tumors (12.7%) and was strongly related to disease stage (23% of 69 stage III or IV tumors were IHC* versus 4% of 74 stage O-II tumors; P < 0.001, Fisher's exact test). The methods of polymerase chain reaction, single-strand conformational polymorphism, and direct sequencing were used to identify mutations, predominantly missense single-base substitutions in exons 5, 7, or 8 in 9 of 14 IHC* cases but in none of 20 IHC~cases; 5 of these mutations were G:C-»A:T transitions at CpG dinucleotides. These data indicate that mutated p53 alÃ-elesare quite uncommon in early prostate cancers but are found in 20-25% of advanced cancers, suggesting a role for p53 mutation in the progression of at least a subset of prostate cancers.

Research paper thumbnail of The assessment of HER2 status in breast cancer: the past, the present, and the future

Pathology International, 2016

Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved... more Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semiquantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.

Research paper thumbnail of Comment on: The influence of menstrual cycle phase on surgical treatment of primary breast cancer: Have we made any progress over the past 13 years? Author's reply

Journal of the National Cancer Institute, 2002

Research paper thumbnail of Method of quantitative immunohistochemistry and in situ hybridization

Research paper thumbnail of Suppression of interleukin 2 production by sera obtained from hypersensitivity granuloma-bearing mice with defective T cell-mediated immune responses

Immunobiology, Feb 28, 1989

Hypersensitivity pulmonary granulomas were able to induce by the intratracheal injection of antig... more Hypersensitivity pulmonary granulomas were able to induce by the intratracheal injection of antigen-conjugated Sepharose 4B beads into immunized mice. The mice with hypersensitivity granulomas showed a lack of T cell-mediated immune responses to antigens both in vivo (delayed type footpad reaction) and in vitro (lymph node cell proliferation) in association with impaired interleukin 2 (IL 2) production by suppressor cells in lymph nodes. However, no immunosuppressive factors were detected in the granuloma lesions. In the present study, we describe that the sera obtained from these mice contain suppressive factor(s) capable of inhibiting IL 2 production by immune lymph node cells. The appearance of serum suppressor factor(s) is correlated well with inhibition of delayed hypersensitivity in such mice. Partial characterization of suppressor factor(s) showed it is absorbed by T cells and may be proteins. The approximate molecular weight of the factor ranged from 12 to 67 kd. These results suggest that the suppressive mechanisms such as the suppressor cells and serum inhibitory factor(s) may be responsible for the impaired IL 2 production and, therefore, for the lack of both in vivo and in vitro expressions of T cell-mediated immune responses to antigens in mice with hypersensitivity granulomas.

Research paper thumbnail of Compositions and Methods of Use of Het

Research paper thumbnail of Methods and compositions in breast cancer diagnosis and therapeutics

Research paper thumbnail of Improved methods of estimating mitotic activity in solid tumors