The optimized priming effect of FGF-1 and FGF-2 enhances preadipocyte lineage commitment in human adipose-derived mesenchymal stem cells.

The cell-assisted lipotransfer technique, integrating adipose-derived mesenchymal stem cells (ADMSCs), has transformed lipofilling, enhancing fat graft viability. However, the multipotent nature of ADMSCs poses challenges. To improve safety and graft vitality and to reduce unwanted lineage differentiation, this study refines the methodology by priming ADMSCs into preadipocytes-unipotent, self-renewing cells. We explored the impact of fibroblast growth factor-1 (FGF-1), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF), either alone or in combination, on primary human ADMSCs during the proliferative phase. FGF-2 emerged as a robust stimulator of cell proliferation, preserving stemness markers, especially when combined with EGF. Conversely, FGF-1, while not significantly affecting cell growth, influenced cell morphology, transitioning cells to a rounded shape with reduced CD34 expression. Furthermore, co-priming with FGF-1 and FGF-2 enhanced adipogenic potential, limiting osteogenic and chondrogenic tendencies, and possibly promoting preadipocyte commitment. These preadipocytes exhibited unique features: rounded morphology, reduced CD34, decreased preadipocyte factor 1 (Pref-1), and elevated C/EBPα and PPARγ, alongside sustained stemness markers (CD73, CD90, CD105). Mechanistically, FGF-1 and FGF-2 activated key adipogenic transcription factors-C/EBPα and PPARγ-while inhibiting GATA3 and Notch3, which are adipogenesis inhibitors. These findings hold the potential to advance innovative strategies for ADMSC-mediated lipofilling procedures.

Blue Wheals and Blue Angioedema Induced by Blue Dyes: A Systematic Review.

BACKGROUND: Blue wheals and blue angioedema, the adverse reactions to blue dye injections with or without anaphylaxis, are poorly defined. OBJECTIVE: The objective is to review the characteristics (ie, sex and age at onset, interval between blue dye injection and symptom onset, clinical manifestations, duration of blue wheals or angioedema), natural courses, and treatments of blue dye adverse reactions. METHODS: A review of the articles published through July 2021 was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations. RESULTS: Across 523 patients (175 studies) with any adverse reactions to blue dye injections, wheals, angioedema, or both occurred in 193 patients (36.9%). Of these 193 patients, 68 patients (35.2%) developed blue wheals or angioedema, 118 (61.1%) had ordinary wheals or angioedema (nonbluish), and 7 had both (3.6%). We reviewed 169 patients with available data (99 with ordinary lesions and 70 with blue lesions). Patent blue violet had the highest rate of inducing blue wheals or angioedema (odds ratio 4.9). Almost half of the patients with blue wheals or angioedema developed systemic symptoms; and of those with systemic symptoms, all except 1 progressed to anaphylaxis. On-demand treatments with antihistamines, corticosteroids, and epinephrine were commonly used and effective. CONCLUSIONS: Using blue dyes can lead to blue wheals or angioedema and systemic reactions. In patients with a history of a severe allergic reaction to a blue dye, repeat administration of a blue dye should be used only after carefully weighing all the risks and benefits.

Performance of a simplified nutrition screening tool for outpatient radiotherapy cancer patients.

Public hospitals in Thailand recently adopted a new nutrition screening tool to satisfy documentation requirements for reimbursements through the diagnosis-related group system. However, data on the performance of this instrument remains limited. This study was designed to assess the validity and cutoff points of the Society of Parenteral and Enteral Nutrition of Thailand (SPENT) nutrition screening tool against the patient-generated subjective global assessment (PG-SGA) and malnutrition diagnostic criteria proposed by the global leadership initiative on malnutrition (GLIM) in cancer patients receiving outpatient radiation therapy. A cross-sectional study of 350 patients was conducted from August 2018 to September 2020. All patients were screened for malnutrition using the SPENT nutrition screening tool. The instrument's sensitivity, specificity, positive predictive value, negative predictive value, and agreement were calculated using either the PG-SGA or GLIM malnutrition diagnosis as benchmarks. The cutoff that gave the highest sensitivity and specificity of the SPENT nutrition screening tool was selected. The mean age standard deviation of the 350 cancer patients was 59.9 (13.9) years, and 191 (54.6%) were men. Head and neck cancers were the most common type (35.7%). Against PG-SGA and GLIM malnutrition diagnosis, the SPENT nutrition screening tool demonstrated good sensitivity (85.3% and 82.8%), specificity (84.1% and 59.4%), positive predictive value (90.5% and 64.0%), negative predictive value (76.3% and 79.9%), with moderate strength of agreement (Cohen kappa 0.678, P < .001 and 0.414, P < .001). Using only the first 2 out of 4 questions revealed an acceptable sensitivity and specificity. The SPENT nutrition screening tool is an accurate, sensitive, and specific tool for malnutrition screening in cancer patients receiving outpatient radiotherapy.

Rapid SARS-CoV-2 antigen detection assay in comparison with real-time RT-PCR assay for laboratory diagnosis of COVID-19 in Thailand.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic continues to spread across the world. Hence, there is an urgent need for rapid, simple, and accurate tests to diagnose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Performance characteristics of the rapid SARS-CoV-2 antigen detection test should be evaluated and compared with the gold standard real-time reverse transcription-polymerase chain reaction (RT-PCR) test for diagnosis of COVID-19 cases. METHODS: The rapid SARS-CoV-2 antigen detection test, Standard™ Q COVID-19 Ag kit (SD Biosensor®, Republic of Korea), was compared with the real-time RT-PCR test, Allplex™ 2019-nCoV Assay (Seegene®, Korea) for detection of SARS-CoV-2 in respiratory specimens. Four hundred fifty-four respiratory samples (mainly nasopharyngeal and throat swabs) were obtained from COVID-19 suspected cases and contact individuals, including pre-operative patients at Siriraj Hospital, Bangkok, Thailand during March-May 2020. RESULTS: Of 454 respiratory samples, 60 (13.2%) were positive, and 394 (86.8%) were negative for SARS-CoV-2 RNA by real-time RT-PCR assay. The duration from onset to laboratory test in COVID-19 suspected cases and contact individuals ranged from 0 to 14 days with a median of 3 days. The rapid SARS-CoV-2 antigen detection test's sensitivity and specificity were 98.33% (95% CI, 91.06-99.96%) and 98.73% (95% CI, 97.06-99.59%), respectively. One false negative test result was from a sample with a high real-time RT-PCR cycle threshold (Ct), while five false positive test results were from specimens of pre-operative patients. CONCLUSIONS: The rapid assay for SARS-CoV-2 antigen detection showed comparable sensitivity and specificity with the real-time RT-PCR assay. Thus, there is a potential use of this rapid and simple SARS-CoV-2 antigen detection test as a screening assay.

Clinical validation of a Cas13-based assay for the detection of SARS-CoV-2 RNA.

Nucleic acid detection by isothermal amplification and the collateral cleavage of reporter molecules by CRISPR-associated enzymes is a promising alternative to quantitative PCR. Here, we report the clinical validation of the specific high-sensitivity enzymatic reporter unlocking (SHERLOCK) assay using the enzyme Cas13a from Leptotrichia wadei for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-the virus that causes coronavirus disease 2019 (COVID-19)-in 154 nasopharyngeal and throat swab samples collected at Siriraj Hospital, Thailand. Within a detection limit of 42 RNA copies per reaction, SHERLOCK was 100% specific and 100% sensitive with a fluorescence readout, and 100% specific and 97% sensitive with a lateral-flow readout. For the full range of viral load in the clinical samples, the fluorescence readout was 100% specific and 96% sensitive. For 380 SARS-CoV-2-negative pre-operative samples from patients undergoing surgery, SHERLOCK was in 100% agreement with quantitative PCR with reverse transcription. The assay, which we show is amenable to multiplexed detection in a single lateral-flow strip incorporating an internal control for ribonuclease contamination, should facilitate SARS-CoV-2 detection in settings with limited resources.

Impact of Obesity on Outcomes of Operable Breast Cancer: A Retrospective Cohort Study.

OBJECTIVE: Obesity is increasing worldwide. Previous studies of the impact of obesity on breast cancer outcomes have reported conflicting results. We investigated the association of obesity and breast cancer survival in Thai patients. METHODS: Medical records of operable breast cancer patients diagnosed and treated at Siriraj Hospital between January 2004 and December 2011 were reviewed. Demographic data, tumor characteristics, stage, treatment and adverse event were described. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2 using Asian's cutoff value.  Survivals in both obese and non-obese patient groups were analyzed. RESULTS: A total of 400 patients were included, 200 in each group. Obese patients were older and associated with more comorbidity. Obesity was associated with larger tumor size (p = 0.011), greater numbers of lymph node involvement (p = 0.003) and more advanced stage (p = 0.01). Obese patients were more likely to receive less adjuvant chemotherapy and hormonal treatment. There was no statistically significant difference in disease-free survival (DFS) (Hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.46 to 1.13) and overall survival (OS) (HR 0.77, 95% CI 0.43 to 1.39) between obese and non-obese patients. Interestingly, obesity was associated with fewer complications from chemotherapy than non-obese patients (p = 0.047). CONCLUSION: Obesity had no adverse prognostic impact association on both DFS and OS in Thai patients with operable breast cancer, although obese patients more often presented with larger tumor and higher numbers of lymph node involvement.
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Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

Nipple-areola complex reconstruction.

Nipple areolar reconstruction (NAC) was introduced since 1940s and evolved as parallel with breast reconstruction since era of breast cancer treatment. It consists of nipple and areolar reconstruction. Ideal reconstruction of the NAC requires symmetry in position, size, shape, texture, and pigmentation and permanent projection. There are many innovative ways to create a nipple and each method has its unique characteristics that apply to certain breast types. NAC reconstruction techniques comprises of composite nipple grafts, local flap, flaps with autologous graft augmentation, flaps with alloplastic augmentation and flaps with allograft augmentation. Areolar reconstruction by using skin grafting and tattooing are the easiest and most common techniques. With the evolution of techniques and technology, perhaps the newer methods of NAC reconstruction can produce promising long-lasting aesthetically acceptable result with minimal morbidity.

Improving breast cancer detection using ultrasonography in asymptomatic women with non-fatty breast density.

BACKGROUND: Mammography (MX) is a reliable modality for detection of breast cancer in asymptomatic women. Use of additional whole breast ultrasonography (US) for breast cancer screening is widely recognized, in particular in women with dense breast parenchyma. PURPOSE: To determine the subgroup of women, according to breast density and age, who receive most benefit from US following MX for detection of breast cancer in an asymptomatic condition. MATERIAL AND METHODS: The study was conducted in asymptomatic women who had non-fatty breast parenchyma using MX and US during January 2006 and December 2007. Mammographic breast density was classified as recommended by ACR BI-RADS lexicon. Non-fatty breast referred to D2, D3, and D4. US was performed by the same radiologists who interpreted MX with a handheld machine during the same visit. Data on demographics, cancer detection rate (CDR), and incremental cancer detection rate (ICDR) were analyzed using 95% confident interval (CI). RESULTS: Of 14,483 breast cancer screenings in women who had non-fatty breast density, 115 cancers were documented. The mean age of cancer patients was 49.6 years. Of 115 cancers, 105 were evidenced on images (31 with MX alone, 19 with US alone, and 55 with both MX and US). Overall CDR was 7.9 per 1000 examination (95% CI, 6.5-9.5). CDR for MX only (MX-CDR) was 6.5 per 1000 examinations (95% CI, 5.2-7.9). Additional US could significantly improve CDR (P < 0.001; 95% CI, 0.9-2.2); US-ICDR was 1.4 per 1000 examinations. According to age group, the group of 40-59 years had statistically significant improvement of ICDR (P < 0.001). The ICDR was highest in D4 breast density (D4) (US-ICDR = 2.5 per 1000 examinations). CONCLUSION: Use of US adjunct to MX for detection of breast cancer in asymptomatic non-fatty, average-risk women for detection of breast cancer is a promising diagnostic procedure. A significant benefit was documented, in particular, in women aged 40-59 years old, and in women with D4 breast density.

Metaplastic carcinoma of the breast with transformation from adenosquamous carcinoma to osteosarcomatoid and spindle cell morphology.

Metaplastic carcinoma of the breast refers to a heterogenous group of mammary carcinomas that contain a mixture of various cell types, including squamous cells, spindle cells and/or a mesenchymal component, such as bone or cartilage. To the best of our knowledge, the clinical course of a tumour that has undergone a transformation from one type of metaplastic carcinoma to another subtype has not previously been reported. The present study reports the five-year clinical and pathological course of a metaplastic breast carcinoma in a 55-year-old female, who was diagnosed with a sclerosing fibroadenomatous nodule with osseous metaplasia and focal atypia. A recurrent tumour was documented four years later, showing a predominant component of osteosarcoma with adenosquamous carcinoma. Upon pathological review of the initial mass, the diagnosis was changed to low-grade adenosquamous carcinoma. The patient was treated with breast conserving therapy. However, one year later, a recurrent metaplastic carcinoma with spindle cell morphology was documented and surgically removed by mastectomy. Subsequently, pulmonary invasion of the chest wall occurred and the patient eventually succumbed due to the invasive nature of the disease.

Ultrasonographic characteristics of mammographically occult small breast cancer.

PURPOSE: To analyze significant ultrasonographic findings of small malignant breast mass (≤10 mm) which were occult on mammography. METHODS: The study included 190 small breast masses (≤10 mm), demonstrated on breast ultrasonography, but not mammography. Histopathology (when the masses were biopsied) or serial breast ultrasonography (for at least 24 months) were used to confirm benign or malignant condition of the masses. Univariate and multivariate logistic regression analysis were used to identify significant characteristic malignant findings on ultrasonography. RESULTS: Of 190 masses, 46 were cancer, and 144 were benign. On multivariate analyses, irregular shape (odds ratio [OR], 10.4) and not circumscribed margin (OR, 31.6) were significant features to differentiate between benign and malignant breast masses. However, low width/anteroposterior ratio, echogenic halo, hypoechogenecity and posterior acoustic shadow, which were predictors for malignancy in large breast mass, were not documented in small mass. CONCLUSION: In conclusion, irregular shape and not circumscribed margin detected during ultrasonography were strong predictive signs of malignancy for small malignant breast mass.

Ewing's sarcoma and primitive neuroectodermal tumour (ES/PNET) presenting as a breast mass.

Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) is a rare tumour usually detected in young individuals and uncommonly found within the breast tissue. In this case report, we examined a 46-year-old patient, who developed a lump on her breast and was later diagnosed with ES/PNET. Clinical presentation, age at development and radiological findings were of interest and were discussed. Diagnosis of the tumour was confirmed using various immunohistochemical studies and the presence of a translocation, t(11;22). A literature review of this rare condition was also included.

Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women.

Expression of estrogen-receptor (ER), progesterone-receptor (PR) and HER-2 has recently been linked with various breast cancer subtypes identified by gene microarray. This study aimed to document breast cancer subtypes based on ER, PR and HER-2 status in Thai women, where expression of these subtypes may not be similar to those evident in Western women. During 2009 to 2010, histological findings from 324 invasive ductal carcinomas (IDC) at Siriraj Hospital were studied. Various subtypes of IDC were identified according to expression of ER, PR and HER-2: luminal-A (ER+;PR+/-;HER-2-), luminal-B (ER+;PR+/-;HER-2+), HER-2 (ER-;PR- ;HER-2+) and basal-like (ER-;PR-;HER-2-). As well, associations of tumor size, tumor grade, nodal status, angiolymphatic invasion (ALI), multicentricity and multifocality with different breast cancer subtypes were studied. Of 324 IDCs, 143 (44.1%), 147 (45.4%), 15 (4.6%) and 12 (3.7%) were T1, T2, T3 and T4, respectively. Most tumors were grade 2 (54.9%) and had no nodal involvement (53.4%). According to ER, PR and HER-2 status, 192 (59.3%), 40 (12.3%), 43 (13.3%) and 49 (15.1%) tumors were luminal-A, luminal-B, HER-2 and basal-like subtypes. HER-2 subtype presented with large tumor (p=0.04, ANOVA). Luminal-A IDC was associated with single foci (p<0.01, χ2). HER-2 and basal-like subtypes were likely to have high tumor grade (p<0.01, χ2). In addition, HER-2 subtype had higher number of nodal involvement (p=0.048, χ2). In conclusion, the luminal-A subtype accounted for the majority of IDCs in Thai women. Percentages of HER-2 and basal-like IDCs were high, compared with a recent study from the USA. The HER-2 subtype was related with high nodal invasion. The findings may highlight biological differences between IDCs occurring in Asian and Western women.

Breast cancer chemoresistance: emerging importance of cancer stem cells.

Cancer stem cells (CSCs) have recently been documented in solid tumours. Evidence has suggested that CSCs are involved in carcinogenesis, tumour invasion and metastases, and resistance to various forms of therapies, including chemotherapy. Breast CSCs are characterised by the expression of CD44 but lack of CD24 (CD44(+)/CD24(-) cells). The mechanisms involved in chemoresistance of breast CSCs are complex and not clearly defined. Overexpression of ABC transporters, detoxification enzymes (aldehyde dehydrogenase), low cell turn over rate and the ability to activate the DNA check point response are possibly all involved. Innovative therapies, based on a better understanding of CSCs, should lead to enhanced and long-term cure rates in breast cancer.

Annexins in human breast cancer: Possible predictors of pathological response to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy is used in women who have large or locally advanced breast cancers. However, up to 70% of women who receive neoadjuvant chemotherapy fail to achieve a complete pathological response in their primary tumour (a surrogate marker of long-term survival). Five proteins, previously identified to be linked with chemoresistance in our in vitro experiments, were identified histochemically in pre-treatment core needle biopsies from 40 women with large or locally advanced breast cancers. Immunohistochemical staining with the five proteins showed no single protein to be a predictor of response to chemotherapy. However, pre-treatment breast cancer specimens that were annexin-A2 positive but annexin-A1 negative correlated with a poor pathological response (p=0.04, Fisher's exact test). The mechanisms by which annexins confer chemoresistance have not been identified, but may be due to inhibition of apoptosis. Annexin-A1 has been shown to enhance apoptosis, whilst annexin-A2, by contrast, inhibits apoptosis.

Predicting response to neoadjuvant chemotherapy in breast cancer: molecular imaging, systemic biomarkers and the cancer metabolome (Review).

The ability to predict the response to neoadjuvant chemotherapy (NAC) prior to or shortly after commencing treatment, in women with large or locally advanced breast cancers, would not only prevent patients from experiencing unnecessary drug morbidity but also reduce the high cost associated with drug usage and utilisation of resources with NAC. Ability to estimate residual cancer volume after NAC is of clinical relevance to subsequent therapeutic surgical options. Various approaches, using conventional histopathological characteristics and imaging modalities to evaluate and predict the response to NAC, have not been able to provide accurate and reliable data. Novel biomolecular imaging, new biomarkers and recent cancer genomic and proteomic profiling, introduced into clinical practice, have produced preliminary promising results. We describe and discuss these molecular characteristics and approaches and their applications to NAC in breast cancer management.

Ex vivo recovery and activation of dysfunctional, anergic, monocyte-derived dendritic cells from patients with operable breast cancer: critical role of IFN-alpha.

BACKGROUND: Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses. RESULTS: Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-alpha+IFN-alpha) or 3 CCM (GM-CSF+IL-4+TNF-alpha) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001). CONCLUSION: Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-alpha. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-alpha. However, 4 CCM containing IFN-alpha generated-PBDCs, do not produce and secrete IL-12p70 in vitro.

Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis.

Pathogenic bacteria use quorum-sensing signal molecules to co-ordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. In the present study, we have examined the impact of these molecules on normal human immune function in vitro and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in the sera of patients. Quorum-sensing signal molecules inhibited normal dendritic cell and T-cell activation and proliferation, and down-regulated the expression of co-stimulatory molecules on dendritic cells; in MLDCRs (mixed lymphocyte dendritic cell reactions), secretion of IL (interleukin)-4 and IL-10 was enhanced, but TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and IL-6 was reduced. Quorum-sensing signal molecules induced apoptosis in dendritic cells and CD4(+) cells, but not CD8(+) cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T-lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4(+) Th1/Th2 (T-helper 1/2) cell apoptotic rate, and modified Th1/Th2 cell cytokine profiles in MLDCRs were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of quorum-sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that quorum-sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis.

18F-FDG dual-headed gamma camera PET in detection of axillary nodal disease in patients with large or locally advanced breast cancer: possible alternative staging of axilla.

Positron emission tomography (PET) has been used in staging the axilla. Gamma Camera PET (GCPET) is a cost effective alternative, but poorly studied. The aim of this study was to assess GCPET in demonstrating metastatic deposits in axillary nodes in patients with a high likelihood of nodal disease. Twenty-seven women with large (T2, T3 or T4) or advanced breast cancer (N1, N2 or M1) were recruited. All patients underwent axillary lymph node removal or biopsy (fine needle aspiration cytology (FNAC) or core cut) and whole body GCPET imaging. Images were reported anonymously and compared with the histological findings. Twenty-one patients proceeded to surgery and 10 had tumour-involved axillary nodes; GCPET was positive in 8 of these. The remaining 6 patients underwent core cut or FNAC of the axillary nodes, 2 of which contained a tumour. GCPET was positive in both cases. Thus, the diagnostic values were: sensitivity 83%, specificity 100%, positive predictive value 100%, negative predictive value 88% and accuracy 93%. In conclusion, GCPET is a reliable method and can be performed in a district general hospital and detecting disease in axillary nodes in certain patients, possibly obviating the need for surgery.

Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs.

Chemoresistance is a poor prognostic factor in breast cancer and, thus, presents a significant clinical challenge. The mechanisms of chemoresistance involve multiple complex biological processes. This study aims to identify common contributory factors to chemoresistance in breast cancer by comparing protein expression profiles of chemosensitive MCF-7 breast cancer cells and cells resistant to two different commonly used anti-cancer drugs (adriamycin and paclitaxel). Expression of the ATP binding cassette transporter, P-glycoprotein (P-gp), in breast tumours has previously been found to correlate with poor prognosis in vivo and, accordingly, we confirmed overexpression of P-gp in both adriamycin- and paclitaxel-resistant MCF-7 cells. Using two-dimensional gel electrophoresis and MALDI-TOF peptide mass fingerprinting, we identified 20 proteins differentially expressed between chemosensitive, adriamycin-resistant and paclitaxel-resistant MCF-7 cells. Cytokeratin-8, keratin-19, Hsp-27, 14-3-3 epsilon, annexin-A2 and phosphoglycerate kinase-1 showed altered expression in both adriamycin- and paclitaxel-resistant cells. Validation of a number of these changes was confirmed by Western blotting. Our findings provide further insights into the complex mechanisms of chemoresistance, as well as representing an attractive starting point for the identification of potential protein biomarkers to predict response to chemotherapy in breast cancer in vivo.