Image-based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno-oncology Biomarker Working Group on Breast Cancer.

Recent advances in the field of immuno-oncology have brought transformative changes in the management of cancer patients. The immune profile of tumours has been found to have key value in predicting disease prognosis and treatment response in various cancers. Multiplex immunohistochemistry and immunofluorescence have emerged as potent tools for the simultaneous detection of multiple protein biomarkers in a single tissue section, thereby expanding opportunities for molecular and immune profiling while preserving tissue samples.

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results.

Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based).

Conventional Microscopical versus Digital Whole-Slide Imaging-Based Diagnosis of Thin-Layer Cervical Specimens: A Validation Study.

Background: Whole-slide imaging (WSI) has been implemented in many areas of pathology, but primary diagnostics of cytological specimens are lagging behind. One of the objectives of viewing scanned whole-slide images from histological or cytological specimens is remote exchange of knowledge and expertise of professionals to increase diagnostic accuracy. We compared the scoring results of our team obtained in double readings of two different data sets: conventional light microscopy (CLM) versus CLM and CLM versus WSI.

The American College of Radiology and the American Brachytherapy Society practice parameter for the performance of low-dose-rate brachytherapy.

Brachytherapy is the use of radionuclides to treat malignancies or benign conditions by means of a radiation source placed close to or into the tumor or treatment site. This practice parameter refers only to the use of radionuclide brachytherapy. Brachytherapy alone or combined with external beam therapy plays an important role in the management and treatment of patients with cancer.

Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report.

In 2005, the National Institutes of Health (NIH) Chronic Graft-versus-Host Disease (GVHD) Consensus Response Criteria Working Group recommended several measures to document serial evaluations of chronic GVHD organ involvement. Provisional definitions of complete response, partial response, and progression were proposed for each organ and for overall outcome. Based on publications over the last 9 years, the 2014 Working Group has updated its recommendations for measures and interpretation of organ and overall responses.

Diagnosis and management of an isolated pediatric plexiform neurofibroma involving the hepatic and celiac plexus using multimodality approach: problem solving with diffusion-weighted magnetic resonance imaging.

Plexiform neurofibroma with involvement of the gastrointestinal tract is a very rare entity in children. Here, we present a rather unique case of a 9-year-old boy with no clinical signs or features of neurofibromatosis type 1. A periportal mass lesion was incidentally found after performing an ultrasound in this previously healthy child.

Methylation-specific PCR.

Methylation-specific PCR is a rapid method used to determine the methylation status of DNA. Not only does methylation affect the expression of genes in normal cells, but it is now known that disease processes such as cancer can result in abnormal DNA methylation patterns. Methylation-specific PCR can be used to investigate imprinted genes, to assess human tumors for clonality by studying genes inactivated on the X chromosome, and to examine abnormally methylated CpG islands in neoplasia.

Time-targeted therapy (TTT): proof of principle using doxorubicin and radiation in a cultured cell system.

We test the hypothesis that a pulse of the anti-cancer agent doxorubicin renders cells more sensitive to ionizing radiation in a strongly time-specific, dose-specific manner. We have treated cultured cells from a human tumor line, HepG2, with graded doses of two agents: doxorubicin (Dox) and ionizing radiation (XR), delivered in sequence-specific, time-specific, dose-specific patterns. We observe a strong increase in cell killing, up to 120 fold, between pulsed treatment with Dox followed exactly 4 hours later with acute XR.

Cellular survival pathways and resistance to cancer therapy.

Chemotherapy and irradiation induce programmed cell death (apoptosis) in their target cells. Dysregulated apoptosis is a feature that is selected for during tumor formation and contributes to therapeutic resistance. Cell survival in the face of cytotoxic therapy is dictated by both internal properties of the cell, such as status of components of the apoptotic machinery, and its extracellular milieu, such as extracellular matrix (ECM) and growth factor receptor expression and signaling.

AIDS oncology.

New diagnostic approaches to primary central nervous system lymphoma have been developed that may make brain biopsy unnecessary in many instances. Reduced-dose chemotherapy for non-Hodgkin's lymphoma has been shown to be advantageous in a randomized controlled trial. New agents for the treatment of Kaposi's sarcoma are available.

Structural requirements for gp80 independence of human herpesvirus 8 interleukin-6 (vIL-6) and evidence for gp80 stabilization of gp130 signaling complexes induced by vIL-6.

Human herpesvirus 8 interleukin-6 (vIL-6) displays 25% amino acid identity with human IL-6 (hIL-6) and shares an overall four-helix-bundle structure and gp130-mediated STAT/mitogen-activated protein kinase signaling with its cellular counterpart. However, vIL-6 is distinct in that it can signal through gp130 alone, in the absence of the nonsignaling gp80 alpha-subunit of the IL-6 receptor. To investigate the structural requirements for gp80 independence of vIL-6, a series of expression vectors encoding vIL-6/hIL-6 chimeric and site-mutated IL-6 proteins was generated.

Dose intensity for breast cancer: where do we go from here?

Strategies utilizing high-dose chemotherapy for treatment of breast cancer have been the subject of significant controversy over the past decade. Disappointing results from randomized phase III trials in metastatic and high-risk, early stage breast cancer have tempered enthusiasm for this approach. A significant problem with large, randomized phase III trials is that improvements in therapy and supportive care cannot be rapidly incorporated into treatment, and the question under study may quickly become obsolete.

Stereotactic body radiation therapy. Rationale, techniques, applications, and optimization.

Stereotactic body radiation therapy (SBRT) is a rapidly evolving cancer treatment method in which concepts and techniques previously developed for brain tumor radiosurgery are adapted to eradicate tumors elsewhere in the body. The spatial accuracy, conformality, and steep radiation dose gradients of radiosurgery, which have been critical to its success in the treatment of intracranial tumors, are applied in SBRT to treat a variety of extracranial tumors. Early results demonstrate excellent response rates and low toxicity with a variety of hypofractionated dose regimens and localization/immobilization techniques.

Evasion of early cellular response mechanisms following low level radiation-induced DNA damage.

DNA damage that is not repaired with high fidelity can lead to chromosomal aberrations or mitotic cell death. To date, it is unclear what factors control the ultimate fate of a cell receiving low levels of DNA damage (i.e.

Zinc homeostasis in premature infants does not differ between those fed preterm formula or fortified human milk.

The objectives of this study were to compare zinc homeostasis in premature infants enterally fed with either preterm infant formula or fortified human milk; to examine interrelationships of variables of zinc homeostasis; and to examine the findings in relation to estimated zinc requirements of preterm infants. Zinc homeostasis was studied in 14 infants (8 male), with mean gestational age of 31 wk and birth weight appropriate for gestational age, who were exclusively fed either preterm formula (n = 9) or own mother's milk with human milk fortifier (n = 5). Zinc stable isotopes were administered intravenously ((70)Zn) and orally as an extrinsic label ((67)Zn) over multiple feeds for determination of fractional absorption by dual isotope tracer ratio in urine; endogenous fecal zinc was determined by isotope dilution; and exchangeable zinc pool (EZP) size was estimated from linear regression of log-transformed urine (70)Zn enrichment data.

Enhanced radiation response through directed molecular targeting approaches.

In both the pre- and post-human genome sequencing eras, there has been an increase in the understanding of the molecular mechanisms influencing cellular sensitivity to DNA damaging agents such as ionizing radiation. Out of this work have arisen many cellular factors that could be specifically targeted, at the molecular level, to alter the functionality of a single protein or pathway involved in the response to radiation damage as a means to increase cell killing following radiation treatment. As such, there are many promising new combination radio-gene therapy approaches being developed and assessed in pre-clinical and clinical studies for several different malignancies.

Ovarian cancer surgery in Maryland: volume-based access to care.

Purpose: To characterize the patterns of primary surgical care for ovarian cancer in a statewide population according to annual surgeon and hospital case volume.

Methods: The Maryland hospital discharge database was accessed for annual surgeon and hospital ovarian cancer case volume for the time intervals: 1990-1992, 1993-1995, 1996-98, and 1999-2000. Annual surgeon case volume was categorized as low (/=10).

Clinical course and pathologic findings after Gliadel and radiotherapy for newly diagnosed malignant glioma: implications for patient management.

Randomized trials have demonstrated Gliadel improves survival for appropriately selected patients with newly diagnosed malignant glioma. As only limited information is available to guide the management of patients who have Gliadel controlled-release BCNU wafers implanted in the cranial resection cavity prior to radiotherapy (RT), this retrospective review was conducted to describe clinical course, toxicity, and pathologic findings after this therapy for newly diagnosed malignant glioma. Forty-six consecutive patients receiving Gliadel (3.

Gemcitabine plus radiation therapy in the treatment of locally advanced non small-cell lung cancer.

For stage III non small-cell lung cancer, there is a need for better systemic, as well as locoregional, control of the tumor. In an attempt to enhance this locoregional control, systemic chemotherapy has been given currently with radiation therapy. Gemcitabine, a novel deoxycytidine analogue, has been shown to be a potent radiosensitizer.

Biological significance and molecular mechanisms of p53-induced apoptosis.

The recognition that the p53 tumour suppressor gene is frequently inactivated in human cancers has galvanized an intense pursuit of the fundamental mechanisms by which the encoded protein halts malignant transformation and tumour progression. It is now evident that p53 is a multifunctional transcription factor that is intimately involved in the cellular response to stressful stimuli such as DNA damage and hypoxia. In addition to its role in the surveillance mechanisms that arrest cell cycle progression, p53 can also trigger apoptosis in response to DNA damage or oncogenic aberrations that induce aberrant cell cycle progression.

The Satisfaction with Life Domains Scale for Breast Cancer (SLDS-BC).

Despite improved overall survival rates, the diagnosis of breast cancer continues to generate fear and turmoil in the lives of many women. All phases related to diagnosis, treatment, and recovery create challenges and problems that patients and survivors must face. Clearly, at the time of diagnosis and during the first phases of treatment, patients experience uncertainty, confusion, and distress.

A randomized phase II evaluation of bryostatin-1 (NSC #339555) in persistent or recurrent squamous cell carcinoma of the cervix: A Gynecologic Oncology Group Study.

Objectives: The Gynecologic Oncology Group performed a randomized phase II study to determine the antitumor activity and toxicity of two different schedules of administration of bryostatin-1 in patients with persistent or recurrent squamous cell carcinoma of the cervix.

Methods: Eligible patients were randomized to receive either bryostatin-1 25 mug/m(2) as a 1-h infusion weekly for 3 weeks followed by a 1-week rest (Regimen I) or bryostatin-1 120 mug/m(2) as a 72-h continuous infusion every 2 weeks (Regimen II).

Results: A total of 70 patients were enrolled on this study.

Phase I study of escalating doses of low-dose-rate, locoregional irradiation preceding Cytoxan-TBI for patients with chemotherapy-resistant non-Hodgkin's or Hodgkin's lymphoma.

Purpose: In patients in whom bone marrow transplantation (BMT) fails, recurrence often occurs at sites known to have contained disease before initiating BMT. The purpose of this study was to find the maximal tolerable dose of locoregional irradiation (LRT) between 1000 and 2000 cGy that could be integrated with our Cytoxan-total body irradiation (TBI) BMT conditioning regimen in the treatment of lymphoma.

Methods And Materials: Patients had Hodgkin's or non-Hodgkin's lymphoma in chemotherapy-refractory relapse.