The antibody-drug conjugate (ADC) cAC10-vcMMAE consists of the tubulin inhibitor monomethyl auristatin E (MMAE) conjugated to the chimeric anti-CD30 monoclonal antibody cAC10. This ADC potently interferes with the growth of CD30-positive haematological tumours, including Hodgkin lymphoma (HL) and anaplastic large-cell lymphoma. This study found improved antitumour activity in a preclinical model of HL when SGN-35 was combined with chemotherapeutic regimens such as ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or gemcitabine. Improved efficacy was also observed in high tumour burden models, indicating that combining ADCs with chemotherapeutic agents may be advantageous for the treatment of patients with relapsed or refractory HL.

Background:

While trying to integrate multiple data sets collected by different researchers, we noticed that the sample names were frequently entered inconsistently. Most of the variations appeared to involve punctuation, white space, or their absence, at the juncture between alphabetic and numeric portions of the cell line name.

Results:

Reasoning that the variant names could be described in terms of mutations or deletions of character strings, we implemented a simple version of the Needleman-Wunsch global sequence alignment algorithm and applied it to the cell line names. All correct matches were found by this procedure. Incorrect matches only occured when a cell line was present in one data set but not in the other. The raw match scores tended to be substantially worse for the incorrect matches.

Conclusions:

A simple application of the Needleman-Wunsch global sequence alignment algorithm provides a useful first pass at matching sample names from different data sets.

Introduction

The current standard for treating operable early stage non-small cell lung cancer is surgical resection and for inoperable cases it is external beam radiotherapy. Lung functions are adversely affected with both the above treatments. CyberKnife treatment limits radiation damage by tracking targets moving with each breath. The effect of CyberKnife treatment on pulmonary function tests has not been well documented.

Methods

Lung cancer patients who underwent CyberKnife treatment and had pre- and post-treatment pulmonary function tests were included. Paired t -tests were conducted. We also conducted subgroup analysis.

Results

Thirty-seven patients were included. Median age was 73 years. No statistical difference between mean pre- and post-CyberKnife pulmonary function tests was found.

Discussion

We observed that CyberKnife better preserves lung function status compared to current standards of care. It has shown to have very minimal side effects.

Purpose

Hesketh scores define emetogenicity of single-agent and multiagent single-day chemotherapy. This analysis determined the emetogenicity of multiagent, multiday chemotherapy and the Granisetron Transdermal System (GTDS; Sancuso ^® ).

Methods

This was a retrospective analysis of a multicenter, randomized, double-blind, phase III noninferiority trial of GTDS versus oral granisetron in patients receiving 3 days of multiagent moderately or highly emetogenic chemotherapy, regardless of granisetron formulation. Emesis was defined as vomiting/retching or the use of rescue medication. Logistic regression and classification trees were used to determine the optimal combination of Hesketh scores over the multiagent, multiday regimens for the prediction of emesis.

Results

Of 393 patients, 272 (69.2%) were chemotherapy naïve. The most common types of cancer were lung (30.5%) and gynecologic (21.9%). The most common chemotherapeutic regimen (in 14.2% of patients) was cisplatin plus etoposide on days 1–3. The best binary emesis predictor was day 1 Hesketh score. Patients with a day 1 Hesketh score of 5 had the highest rate of emesis (62.5%) versus patients with a score < 5 (31.7%). For patients with day 1 Hesketh score < 5, only 14.3% of those receiving only one drug on day 1 experienced emesis.

Conclusion

Hesketh emetogenicity scores of individual agents are applicable to multiday, multiagent chemotherapeutic regimens in patients receiving antiemetics.

Basal-like breast cancer has been reported to be the most aggressive and deadly carcinoma sub-type. Patients diagnosed with this subtype have a less than 50% five-year survival. In addition, many studies have reported that this sub-type is more prevalent in specific ethnic groups and is believed to be a key factor that drives certain ethnic disparities in mortality. In order to effectively study this sub-type and determine unique gene expression and biochemical pathways which sustain this cancer’s growth, we sought to identify human breast cancer cell lines that represent a model for the basal-like subtype. Here, we report our findings which indicate the African American cell line CRL-2335 is a true representative of basal-like breast carcinoma.

Living on earth, we are exposed to ultraviolet (UV) light as part of the solar radiation. UVB spectrum light exposure contributes to the development of skin cancer by interacting with pyrimidine pairs to create lesions called cyclobutane pyrimidine dimers. If these lesions are not removed by nucleotide excision repair, they often give rise to C to T transition mutations. Based on these observations, a bioinformatics approach was used to predict the vulnerability of human protein coding genes to UVB induced loss of function mutations. This data was used to evaluate in depth those genes associated with malignant melanoma. In addition, we demonstrate a method of genetically engineering genes that significantly improves resistance to UVB loss of function mutations.

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients.

We report an extremely rare case with a total of 50 fibroadenomas simultaneously presented in bilateral breasts and left axillary accessory breast, up to 8 cm in size, in a 20 year-old Chinese woman. The histopathologic and immunophenotypic features of the fibroadenomas are described and possible underlying pathogenesis is discussed. To our knowledge, this is the first case with such a large number of bilateral multiple breast fibroadenomas in a young female reported in the literature.

BRCA1 is a tumor suppressor protein involved in maintaining genomic integrity through multiple functions in DNA damage repair, transcriptional regulation, cell cycle checkpoint, and protein ubiquitination. The BRCA1-BARD1 RING complex has an E3 ubiquitin ligase function that plays essential roles in response to DNA damage repair. BRCA1-associated cancers have been shown to confer a hypersensitivity to chemotherapeutic agents. Here, we have studied the functional consequence of the in vitro E3 ubiquitin ligase activity and cisplatin sensitivity of the missense mutation D67Y BRCA1 RING domain. The D67Y BRCA1 RING domain protein exhibited the reduced ubiquitination function, and was more susceptible to the drug than the D67E or wild-type BRCA1 RING domain protein. This evidence emphasized the potential of using the BRCA1 dysfunction as an important determinant of chemotherapy responses in breast cancer.