The evolvement of breast cancer therapies: What we have done and where all these head off.

Although, from a therapeutic standpoint, breast cancer (BC) is considerably well-characterized, it still leaves puzzling spots. The Her-2+/PR+/ER+ BC can benefit from the mainstays of anticancer therapy and immunotherapy and overall have a better prognosis. Triple-negative BC, due to the concomitant absence of Her-2/PR/ER receptors, is more challenging and necessitates different strategies. It has been learned that the mainstay anti-BC therapies were initially designed to demolish as many cancer cells as they possibly could. However, the number of reports on the adverse effects of these mainstay therapies has recently been increasing. It underpins efforts to reshape such therapies into much better and safer forms over time. Moreover, some current findings on the molecular markers, which are target-potential, have also shifted the paradigm from radical-to-local-yet-precise-approach to meet the need for a therapy platform that is less cytotoxic to normal cells yet efficiently kills cancer cells.

Acquired lymphedema: Molecular contributors and future directions for developing intervention strategies.

Lymphedema is a debilitating chronic disease that mostly develops as an adverse reaction to cancer treatment modalities such as chemotherapy, surgery, and radiotherapy. Lymphedema also appears to be a deteriorating consequence of roundworm infections, as best represented by filariasis. According to its origin, lymphedema is classified as primary lymphedema and acquired lymphedema. The latter is an acquired condition that, hitherto, received a considerably low attention owing to the less number of fatal cases been reported. Notably, despite the low mortality rate in lymphedema, it has been widely reported to reduce the disease-free survival and thus the quality of life of affected patients. Hence, in this review, we focused on acquired lymphedema and orchestration of molecular interplays associated with either stimulation or inhibition of lymphedema development that were, in vast majority, clearly depicted in animal models with their specific and distinct technical approaches. We also discussed some recent progress made in phytochemical-based anti-lymphedema intervention strategies and the specific mechanisms underlying their anti-lymphedema properties. This review is crucial to understand not only the comprehensive aspects of the disease but also the future directions of the intervention strategies that can address the quality of life of affected patients rather than alleviating apparent symptoms only.

Intronic Variant of MUTYH Gene Exhibits A Strong Association with Early Onset of Breast Cancer Susceptibility in Indonesian Women Population.

OBJECTIVE: Several studies have recently indicated a huge shifting pattern toward early age onset cases in breast cancer (BC) patients. However, the studies exerted relatively limited to the Caucasian population. This preliminary study is aimed to investigate the genetic risk factors for young BC patients specifically in Indonesia population. METHODS: DNA samples were extracted from 79 BC patients aged younger than 40 years old and 90 healthy samples. These DNA samples were sequenced using Illumina NextSeq 500 platform and preprocessed to extract the single-nucleotide polymorphisms (SNPs) data. Firstly, multiple univariate logistic regressions were performed to test the association between each SNP and BC incidence in young patients. Furthermore, to analyze the polygenic effects derived from multiple SNPs, we employed a multivariate logistics regression. RESULTS: There were only 15 SNPs passed our 95% call rate threshold thus subsequently were used in the association test. One of these variants, rs3219493, emerged to be significantly associated with early-onset BC (p-value = 0.025, OR = 3.750, 95% CI = 1.178-11.938). This result is consistent with the multivariate logistic regression model, where the pertinent variant was found statistically significant (p-value = 0.008, OR = 8.398, 95% CI = 1.720-40.920). This variant was identified as an intronic variant within MUTYH gene which has been reported in several published studies to exhibit an association with the incidence of breast cancer in China, Italy and Sephardi Jews population. However, there is no evident this gene impacting the risk of developing early onset of BC in Indonesia population. CONCLUSION: Despite our limitation in terms of sample size analyzed in this preliminary study, our finding on significant association of intronic MUTHY with the early onset of BC in Indonesia led to a broadened insight of population-based unique aspect to being taken into an in-depth account for and advancement of chemotherapy.

Dietary Intake as Determinant Nongenetic Factors to Colorectal Cancer Incidence and Staging Progression: A Study in South Sulawesi Population, Indonesia.

Reports from various population-based studies indicate that the incidence of colorectal cancer may be strongly affected by dietary patterns of the respective populations. The nature of dietary patterns of specific Indonesia population on the risk of colorectal cancer might differ from previously published data with the global population. Therefore, we conducted a study where the dietary pattern in colorectal cancer patient cohorts was compared to age- and population-matched control. We documented 89 colorectal cancer cases and among 173 individuals from the South Sulawesi population. A series of logistic regression and Fisher's exact tests were utilized to test associations of dietary intakes and colorectal cancer risk as well as colorectal cancer staging. Our data demonstrate that vegetable (p-value = 8.70 × 10-26, OR = 0.49) and fruit (p-value = 7.59x10-5, OR = 0.70) intakes are associated with the reduced risk of colorectal cancer incidence. Conversely, acidic food, reheated food, meat, spicy food, and alcohol are associated with the increment case of cancer. Moreover, meat intake (p-value < 0.01) shows a significant association with cancer staging progression. Common dietary pattern is a determinant aspect to the colorectal cancer incidence as well as its staging progression.

CD8+ lymphocytes and apoptosis in typical and atypical medullary carcinomas of the breast.

Medullary breast carcinoma (MBC) is a form of ductal invasive carcinoma (DIC) characterized by an abundant infiltration of the tumour by lymphocytes. MBC has been classified histologically into typical medullary carcinoma (TMC) and atypical medullary carcinoma (AMC), with TMC having a better prognosis than AMC and other DIC. The distribution of CD8+ lymphocytes within tumour nests and lymphocyte tracts, and apoptosis in lymphocytes and tumour cells within tumour nests, were studied in archived formalin fixed and paraffin embedded tissues of TMC and AMC. CD8+ lymphocytes tend to accumulate along the margins of lymphocyte tracts that adjoin tumour nests. There were significantly more CD8+ lymphocytes within tumour nests of TMC than AMC. TMC also tended to have more CD8+ lymphocytes within lymphocyte tracts than AMC. Apoptosis of lymphocytes in contact with tumour cells and of tumour cells in contact with lymphocytes was observed in both AMC and TMC within tumour nests but differences in the proportions of apoptotic tumour cells and lymphocytes between the two tumour types could not be established. The findings are consistent with CD8+ cytotoxic lymphocyte-mediated immunity contributing to the more favourable prognosis for TMC compared to AMC.