Association between pre-existing cardiometabolic comorbidities and the pathological profiles of breast cancer at initial diagnosis: a cross sectional study.

The presence of comorbidities has been associated with later stages of breast cancer diagnosis. It is unclear whether biological mechanisms are partly responsible. We examined the association between the presence of pre-existing comorbidities and tumour profile at initial diagnosis with breast cancer. Data for the present analysis were derived from a prior inception cohort study comprising 2,501 multiethnic women, newly diagnosed with breast cancer between 2015 and 2017 in four hospitals across Klang Valley. At the inception of the cohort, medical and drug histories, height, weight and blood pressure were recorded. Blood samples were taken to measure serum lipid and glucose. Modified Charlson Comorbidity Index (CCI) was calculated using data extracted from medical records. The association of CCI as well as specific comorbidities, with pathological breast cancer profile was analysed. Higher comorbidity burden, namely cardiometabolic conditions were associated with unfavourable pathological features including larger tumours, involvement of >9 axillary lymph nodes, distant metastasis and human epidermal growth factor receptor 2 overexpression. These associations remained largely significant following multivariable analyses. Specifically, diabetes mellitus was independently associated with high nodal metastasis burden. Low level of high-density lipoprotein was associated with larger tumours (>5 cm), and distant metastasis. Evidence from this study seems to support the hypothesis that the later stages of breast cancer diagnosis in women with (cardiometabolic) comorbidities may be partially explained by underlying pathophysiological events.

The significance of CD14 in clear cell renal cell carcinoma progression and survival prognosis.

Purpose: CD14-positive tumour and immune cells have been implicated in cancer progression. This study evaluated the prognostic significance of CD14 immunostaining in clear cell renal cell carcinoma (ccRCC) compared to the adjacent non-cancer kidney, and serum soluble CD14 (sCD14) levels in patients versus controls.Methods: Immunohistochemistry was performed for CD14 on ccRCC and the corresponding adjacent non-cancer kidney tissue from 88 patients. Staining intensity was determined using Aperio ImageScope morphometry. Serum sCD14 was evaluated for 39 ccRCC patients and 38 non-cancer controls using ELISA. CD14 levels were compared with tumour characteristics and survival status.Results: CD14 overall and nuclear immunostaining was higher in ccRCC compared to the adjacent non-cancer kidney tissue. CD14 nuclear immunostaining in the adjacent non-cancer kidney was significantly associated with advanced stage and adverse RCC survival prognosis. Serum sCD14 concentration was elevated in ccRCC patients compared to non-cancer controls and was also significantly associated with tumour stage and worse survival prognosis. Higher CD14 expression, in particular CD14 positive immune cell infiltrates found in the adjacent non-RCC kidney tissue, were associated with tumour progression and poorer prognosis.Conclusion: The levels of CD14 in non-RCC adjacent kidney and serum could be potential prognostic indicators.

CD14 nuclear immunostaining in the adjacent non-RCC kidney and serum sCD14 were significantly associated with RCC stage and adverse survival prognosis. The findings indicate that CD14 may be involved in RCC tumour progression and is a potential prognostic marker.

Characteristics of skin cancers among adult patients in an urban Malaysian population.

There has been a rising incidence of skin cancers among Asians in recent years. We present a retrospective analysis of 106 skin cancers and analysed the demography, clinical subtypes of skin cancers and surgical techniques used for skin cancer treatment. In our population, skin cancers were most frequently basal cell carcinomas and diagnosed among ethnic Chinese patients.

Establishment of epithelial and fibroblast cell cultures and cell lines from primary renal cancer nephrectomies.

Renal cell carcinoma (RCC) is one of the most lethal urogenital cancers and effective treatment of metastatic RCC remains an elusive target. Cell lines enable the in vitro investigation of molecular and genetic changes leading to renal carcinogenesis and are important for evaluating cellular drug response or toxicity. This study details a fast and easy protocol of establishing epithelial and fibroblast cell cultures or cell lines concurrently from renal cancer nephrectomy tissue. The protocol involves mechanical disaggregation, collagenase digestion and cell sieving for establishing epithelial cells while fibroblast cells were grown from explants. This protocol has been modified from previous published reports with additional antibiotics and washing steps added to eliminate microbial contamination from the surgical source. Cell characterisation was carried out using immunofluorescence and quantitative polymerase chain reaction. Eleven stable epithelial renal tumour cell lines of various subtypes, including rare subtypes, were established with a spontaneous immortalisation rate of 21.6% using this protocol. Eight fibroblast cell cultures grew successfully but did not achieve spontaneous immortalisation. Cells of epithelial origin expressed higher expressions of epithelial markers such as pan-cytokeratin, cytokeratin 8 and E-cadherin whereas fibroblast cells expressed high α-smooth muscle actin. Further mutational analysis is needed to evaluate the genetic or molecular characteristics of the cell lines.

Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients.

Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.

Safety Evaluation of Sclerotium from a Medicinal Mushroom, Lignosus cameronensis (Cultivar): Preclinical Toxicology Studies.

Twenty-eight days subacute toxicity studies performed in rats using sclerotial powder of Lignosus cameronensis cultivar was conducted to assess its safety for consumption prior to other scientific investigations on its medicinal benefits, nutraceutical or pharmaceutical application of the mushroom. The study was conducted at 250, 500, and 1000 mg/kg sclerotial powder of L. cameronensis cultivar (n = 5 for each respective dose, on both male and female groups) while control groups received only distilled water. At the end of the study (29th day), the animals were sacrificed followed by blood and organs collection for analysis. Subacute toxicity studies done shows that sclerotial powder of L. cameronensis cultivar at 250, 500, and 1000 mg/kg did not induce treatment related changes on behavioral patterns, gross physical appearance, growth pattern, body weight gain, values of hematological and clinical biochemical panels as well as histopathological findings on kidney, spleen, heart, lung and liver of the experimental rats. The no-observed-adverse-effect level dose for sclerotial powder of L. cameronensis cultivar in 28-days sub-acute toxicity study is determined to be 1000 mg/kg.

Safety assessment of cultivated fruiting body of Ophiocordyceps sinensis evaluated through subacute toxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ophiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora is one of the most renowned traditional Chinese medicine used as tonic, renal, respiratory and reproductive health, promote longevity and overall improvement in quality of life. Natural production of O. sinensis is limited due to its extreme specificity in host range and confined geographic distribution. Therefore, cultivation of the fungus was developed to meet high demand for commercialization as nutraceutical. O. sinensis fruiting body has recently been successfully cultivated in large scale using rice based solid medium, providing wider source options for consumers and scientific researchers. AIMS OF THE STUDY: The present study aims to establish safety profile for the consumption of cultivated fruiting body of O. sinensis (FBOS) by 28-days sub-acute toxicity study in Sprague Dawley rats. MATERIALS AND METHODS: Rats were orally administered with cultivated FBOS at three graded doses (250, 500 and 1000mg/kg), once daily for 28 consecutive days. Control group received distilled water. General observations (gross behavioral changes and toxic symptoms) and body weight of each animal were monitored daily. Haematological, serum biochemical and histopathological analysis were carried out at the end of the experiment (Day 29). RESULTS: No behavioral changes, toxic symptoms or death was observed in rats throughout the dosing period. Cultivated FBOS treatment up to 1000mg/kg did not cause any adverse effect on the growth of the animals. Results from haematology and serum biochemistry revealed no toxic effect following cultivated FBOS treatment at three graded doses for 28 days. In addition, no treatment related histopathological changes were noted in heart, spleen, kidney, lung and liver of the animals. CONCLUSION: The present study revealed that oral administration of cultivated FBOS for 28 days, at dosage up to 1000mg/kg did not pose toxicological concern in rats. Therefore, the no-observed-adverse-effect level (NOAEL) dose of cultivated FBOS in 28-days subacute toxicity study is higher than 1000mg/kg.

Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats.

Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg.

Incidental Splenic Granuloma Due to Burkholderia pseudomallei: A Case of Asymptomatic Latent Melioidosis?

We report a rare case of an asymptomatic latent melioidosis lesion in a posttraumatic splenectomy specimen from a diabetic patient. The 2-cm yellowish, lobulated lesion was found in the splenic parenchyma well away from the traumatized areas. Microscopically, it consisted of a central area of necrosis and exudate surrounded by macrophages, epithelioid cells, lymphocytes, and occasional multinucleated giant cells. Burkholderia bacilli were detected by a novel in situ hybridization (ISH) assay, and confirmed by polymerase chain reaction and sequencing to be Burkholderia pseudomallei. As melioidosis was not suspected initially, bacterial culture was not done but electron microscopy showed morphologically viable and dividing bacilli in the lesion. Moreover, the surgical wound became infected with B. pseudomallei several days post-surgery. After treatment with ceftazidime and trimethoprim/sulfamethoxazole, the wound infection cleared. We believe this could be a unique case of asymptomatic latent melioidosis in the spleen. In endemic countries, chronic granulomas should be investigated for B. pseudomallei infection, and if available, ISH may be helpful for diagnosis.