5 research outputs found
Myosin binding protein C: implications for signal-transduction
Myosin binding protein C (MYBPC) is a crucial component of the sarcomere and an important regulator of muscle function. While mutations in different myosin binding protein C (MYBPC) genes are well known causes of various human diseases, such as hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy as well as skeletal muscular disorders, the underlying molecular mechanisms remain not well understood. A variety of MYBPC3 (cardiac isoform) mutations have been studied in great detail and several corresponding genetically altered mouse models have been generated. Most MYBPC3 mutations may cause haploinsufficiency and with it they may cause a primary increase in calcium sensitivity which is potentially able to explain major features observed in HCM patients such as the hypercontractile phenotype and the well known secondary effects such as myofibrillar disarray, fibrosis, myocardial hypertrophy and remodelling including arrhythmogenesis. However the presence of poison peptides in some cases cannot be fully excluded and most probably other mechanisms are also at play. Here we shall discuss MYBPC interacting proteins and possible pathways linked to cardiomyopathy and heart failure
Markers of drug resistance in relapsing colon cancer
Purpose: 5-Fluorouracil failure and drug resistance. which often occurs
during chemotherapy. is still a great obstacle to the success of human
colon cancer treatment. Thus. the comparative study of markers of drug
resistance in cancer cells before and after chemotherapy may be
extremely helpful in the selection of the appropriate chemotherapeutic
drug in colon cancer patients who fail adjuvant treatment with
5-fluorouracil. In the present study we examined the differential
expression of three multidrug resistance-related proteins (i.e.,
P-glycoprotein, MRP, and LRP) and of topoisomerase IIalpha in a series
of 20 primary colon carcinomas and their recurrences. Methods: All
markers were determined at tissue level by three-step
immunohistochemistry using appropriate monoclonal antibodies. and the
markers’ immunopositivity was quantified by image analysis. In addition.
Feulgen stain was used for the assessment of nuclear DNA content of
malignant cells at their primary location. Results: Some degree of
aneuploidy was detected in all primary carcinomas. The immunoexpression
of the three multidrug resistance-related proteins did not change
significantly, either qualitatively (positivity vs negativity) or
quantitatively, after chemotherapy. On the contrary, the percentages of
topoisomerase IIalpha-positive malignant cells were significantly
increased in the tumour recurrences by comparison to their primary
locations (P = 0.011). Conclusions: According to our results. increased
topoisomerase IIalpha immunohistochemical expression appears to be part
of the malignant cells’ phenotype in recurrent colon cancers.
Therapeutic options after failure of 5-fluorouracil-based treatment
could therefore include appropriate topoisomerase IIalpha-targeted
drugs
Cyclin D1 protein tissue detection in laryngeal cancer
Cyclin D1 (CCND1) is a set of periodic regulatory proteins that is
believed to govern cell cycle transit from G1 into S phase.
Overexpression of CCND1 leads to abnormal cellular proliferation which
underlies processes of tumorigenesis; CCND1 can thus function as a
cooperative oncogene in cell transformation. In the present study we
investigate the immunohistochemical expression of CCND1 in a
well-documented series of 58 laryngeal squamous cell carcinomas (LSCC)
and search for statistical associations between CCND1 index and various
clinicopathological parameters including several immunomarkers’
expression as well as patients’ disease-free survival. Tissue sections
from archival paraffin blocks were stained using the
avidin-biotin-peroxidase complex method; the H-295 rabbit polyclonal
antibody was applied at dilution of 1: 150. The percentage of CCND1
immunoreactive tumor cells for each tumor was counted by an image
analysis system. CCND1 staining was confined to cell nuclei and, in the
examined samples, ranged from undetectable (i.e. 0% of tumor cells, n =
6) to the majority of tumor cells (i.e. 89% of tumor cells) with mean
value: 15.73%. In tumor adjacent, non invasive lesions, strong CCND1
staining was noticed in areas with cellular atypia. In cases with nodal
metastases, no change in CCND1 expression in the nodal metastases
compared with the primary tumors was observed. p53 protein accumulation
in malignant cells was positively linked with CCND1 index (Mann-Whitney
U: 205.5, p = 0.034). CCND1 expression appears to be an early event in
processes of tumorigenesis and tumor progression in some LSCC. Apart
from p53 protein accumulation, CCND1 immunohistochemical expression does
not seem to correlate with nodal metastasis, disease recurrence or any
other clinicopathological prognostic indicator. Copyright (C) 2005 S.
Karger AG, Basel
Multidrug resistance proteins and topoisomerase II alpha expression in colon cancer: association with metastatic potential
Aims: To investigate the role of multidrug resistance proteins and
topoisomerase IIalpha in colon cancer.
Methods: Tissue sections from 89 Dukes’ stage B-D colon cancer patients
were selected. The expression of multidrug resistance proteins and
topoisomerase IIalpha in primary tumour cells was assessed by standard
immunohistochemistry. The extent of their expression was measured by
image analysis and was correlated with clinicopathological features of
the patients.
Results: P-glycoprotein was associated with the presence of lymph node
metastasis (P=0.005), vessel invasion (P=0.0001) and perineural invasion
(P=0.020).
Conclusions: P-glycoprotein is probably involved in the processes of
local invasion and metastatic dissemination