Expanding the clinical development of bevacizumab

Bevacizumab (Avastin; Genentech, Inc.; South San Francisco, CA) is a recombinant, humanized monoclonal antibody to vascular endothelial growth factor, a key regulator of tumor angiogenesis. Bevacizumab demonstrated potent antitumor activity in preclinical models and has also shown biologic activity and clinical benefit in clinical studies. Notably, a randomized, placebo-controlled phase II trial in renal cell carcinoma demonstrated a significantly longer time to tumor progression with bevacizumab monotherapy. Furthermore, in a phase III trial for untreated advanced colorectal cancer, the addition of bevacizumab to chemotherapy led to significantly longer overall survival and progression-free survival times than chemotherapy alone. The clinical development of bevacizumab has been expanded to include confirmatory phase III trials and exploratory phase II trials in a variety of solid tumors and hematologic malignancies. Treatment regimens being examined include bevacizumab alone and in combination with conventional chemotherapy, radiation, immune therapy, and biologically targeted agents.     

Quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis: a systematic review of the literature

The aim of this study was to review the literature on quality of life among adult patients with neurofibromatosis 1, neurofibromatosis 2 and schwannomatosis, and to identify the specific aspects of quality of life that were studied and reported in this population. We also set out to report predictors of quality of life. Published research reports were included if they described quality of life in this population and met methodological quality according to a list of predefined criteria. Eight studies (7 in NF1, 1 in NF2, 0 in schwannomatosis), conducted between 2001 and 2013, met inclusion criteria. The methodological quality of the eight studies was mostly high according to ratings by predefined criteria. Most studies reported that patients with NF experience decreased quality of life when compared to the general population. Visibility and disease severity were strong predictors of skin-specific quality of life in NF1 patients. However, the majority of findings regarding predictors of quality of life were weak or inconclusive. Given the decreased quality of life in NF patients, it is important to examine more comprehensively the psychosocial factors in this population, especially in patients with NF2 and schwannomatosis. Mind body interventions that address these domains may provide comprehensive and efficacious long term treatment.     

Expanding colorectal cancer screening among minority women

BACKGROUND:

Colorectal cancer screening (CRCS) in the United States is inadequate in minority communities and particularly among those who lack insurance. Finding ways to increase screenings in these minorities presents a healthcare challenge. The authors sought to determine whether offering CRCS at the time of mammography is an effective way to increase CRCS among minority women.

METHODS:

This study was offered to women attending the Breast Examination Center of Harlem (BECH), a community outreach program of Memorial Sloan‐Kettering serving the primarily black and Hispanic Harlem Community. Screening was explained, medical fitness was determined, and colonoscopies were performed. Barriers to screening and ways to overcome them were ascertained. Participants had to be at least 50 years of age without a history of colorectal cancer or screening within the last 10 years.

RESULTS:

There were 2616 women eligible for CRCS, of these women 2005 (77%) refused to participate in the study, and 611 (23%) women were enrolled. There was a high interest in CRCS including among those who declined to participate in the study. The major barrier was lack of medical insurance, which was partially overcome by alternative funding. Of the 611 women enrolled, 337 (55%) went on to have screening colonoscopy. Forty‐nine (15%) women had adenomatous polyps.

CONCLUSIONS:

Offering CRCS to minority women at the time of mammography and without a physician's referral is an effective way to expand screening. Screening colonoscopy findings are similar to those in the general population. Alternatives to traditional medical insurance are needed for the uninsured. Cancer 2011. © 2010 American Cancer Society.     

Expanding the role of blood progenitor cells

Five years ago the haemopoietic growth factors were introducedto clinical practice with the aim of reducing the depth andduration of chemotherapy induced neutropenia. Now, they havea wider remit, with important roles in supporting dose intensivetreatments and mobilising BPC. Similarly, BPC themselves haveuntil now been predominantly used in autologous transplantationfollowing myeloablative treatments. In the next five years wecan expect to see BPC from novel sources manipulated to featurein many new roles, including allogeneic transplantation, multicyclicdose-intensive chemotherapy and gene therapy blood progenitor cells, mobilisation, transplantation     

Lymphomas of T-cell phenotype

Malignant lymphomas disrupt the anatomical organization of lymphoid organs and are recognized by patterns of growth and the morphology of the abnormal cells. The phenotype of these cells can be determined with precision by the demonstration of cell surface receptors and antigenic determinants by standard immunologic procedures. Most B-cells are found within discrete follicles and display characteristic cytologic and immunologic features. Although malignant proliferations of B-cells do not follow normal structural boundaries.     

Management of neurofibromatosis type 2 and schwannomatosis associated peripheral and intraspinal schwannomas: influence of surgery,genetics, and localization

Journal of Neuro-Oncology - Meningiomas that progress despite surgery and radiotherapy represent an unmet medical need. Expression of PD-1 and PDL-1 has been demonstrated in meningiomas and is...     

Immortalization phenotype dissociated from the preneoplastic phenotype in mouse mammary epithelial outgrowths in vivo

Mouse mammary epithelial cells (MMEC) isolated from normal virginBALB/c female mice and grown in cell culture for various lengthsof time were injected into the mammary fat pads of syngenicmice. Of the ductal outgrowths which resulted from the injectedMMEC, four gave rise to outgrowths that were serially transplantedbeyond the lifetime of normal ductal outgrowths. The lifetimeof normal ducts is five or six transplant generations. The fourductal outgrowth lines, termed EL for ‘extended life’,have been serially transplanted for 7, 9, 13 and 14 transplantgenerations. The outgrowths are predominately ductal in morphology,do not exhibit intraductal epitheliosis characteristic of ductalhyperplasias, are ovarian dependent for growth and are responsiveto prolactin-mediated alveolar differentiation. Three of theEL lines, ELS, 7 and 11 have not produced any tumors spontaneously(0/64) and only one tumor after dimethylbenz[a]anthracene (DMBA)treatment (1/30). The fourth line, EL12, differs from the otherthree in the presence of a limited degree of alveolar differentiation.The EL12 line has not produced any spontaneous tumors (0/23)but is somewhat more responsive to DMBA (3/10). We interpretthe EL lines (at least EL11 and EL12) to represent cell populationswhere the immortalized phenotype is dissociated from the hyperplasticphenotype which is characteristic of mouse mammary preneoplasticpopulations. The tumor suppressor gene, p53, is not overexpressedin the EL ductal outgrowths. To our knowledge, this is the firstexample of cell populations in vivo that are immortalized butotherwise normal. As such, they may represent the earliest stageobservable in the genesis of mouse mammary tumors and provideunique cell populations to examine molecular alterations associatedwith the property of immortality.