Acquired chemoresistance has curtailed cancer survival since the dawn of chemotherapy. Accumulating evidence suggests a major role for cancer stem cells (CSC) in chemoresistance, although their involvement in acquired resistance is still unknown. The use of aspirin has been associated with reduced cancer risk and recurrence, suggesting that the anti-inflammatory drug may exert effects on CSCs. In this study, we investigated the contribution of CSCs to acquired chemoresistance of breast cancer and the avenues for reversing such effects with aspirin. We observed that the residual risk of recurrence was higher in breast cancer patients who had acquired chemoresistance. Treatment of preexisting CSCs with a genotoxic drug combination (5-fluorouracil, doxorubicin, and cyclophosphamide) generated an NFkB-IL6-dependent inflammatory environment that imparted stemness to nonstem cancer cells, induced multidrug resistance, and enhanced the migration potential of CSCs. Treatment with aspirin prior to chemotherapy suppressed the acquisition of chemoresistance by perturbing the nuclear translocation of NFkB in preexisting CSCs. Therefore, disruptions to the NFkB-IL6 feedback loop prevented CSC induction and sensitized preexisting CSCs to chemotherapy. Collectively, our findings suggest that combining aspirin and conventional chemotherapy may offer a new treatment strategy to improve recurrence-free survival of breast cancer patients.

COX-2 regulates tumour growth, invasion and metastasis in breast cancer. This study investigated the association between COX-2 expression in human breast cancer versus the expression of ER, PR, HER-2/neu, as well as its association with other established prognostic indicators like age, menopausal status, tumour size, lymph nodal status, stage, grade, NPI and histological subtype, and aims to validate the role of overexpression of COX-2 as a prognostic marker in patients with breast cancer in Indian subcontinent. In this hospital based study of 123 breast cancer patients (Group-A) and 76 female patients with benign breast disease (Group-B) attending a Comprehensive Breast Clinic at a reputed institute in Eastern India, COX-2 protein expression was measured from breast tissue using the Western Blot Technique. COX-2 mRNA expression was measured by RT-PCR Technique. ER, PR and HER-2/neu status was measured by immunohistochemistry methods. COX-2 was not expressed in the control group. The proportion of COX-2 positive tumours was significantly higher in patients of age . Risk of COX-2 positivity was found to be 2.74 times more for postmenopausal status, 6.90 times more for large size tumours (≥ 2.5), 34.37 times more for node positive tumours, 9.26 times more with ER negative patients and 5.88 times more for PR negative patients. COX-2 expression is associated with established indicators of poor prognosis such as postmenopausal status, age >50 year, advanced stage of disease, large tumour size, higher grade, lymph node metastasis, NPI≥5.4, ER negativity, PR negativity and HER-2/neu positivity. Thus, COX-2 expression implies aggressive tumour biology, and may play an important role as a prognostic marker.

Although the role of metastatic cancer stem cells (mCSCs) in tumor progression has been well documented, our study reveals a hitherto unidentified role of tumorigenic intrinsic CSCs (iCSCs) in breast cancer metastasis. We show that unlike highly migratory mCSCs residing in the breast tumor disseminating/peripheral regions, iCSCs populate the inner mass of the tumor and are non-migratory. However iCSCs, via paracrine signaling, induce conversion of non-stem cancer cells to CSCs that (i) are identical to the previously reported mCSCs, and (ii) in contrast to iCSCs, express chemokine receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), which is crucial for their metastatic potential. These mCSCs also demonstrate high in vivo tumorigenicity. Physical non-participation of iCSCs in metastasis is further validated in vivo, where only mCSCs are found to exist in the metastatic sites, lymph nodes and bone marrow, whereas the primary tumor retains both iCSCs and mCSCs. However, iCSCs ensure metastasis since their presence is crucial for deliverance of highly metastatic CXCR4(+) mCSCs to the migrating fraction of cells. Cumulatively, these results unveil a novel role of iCSCs in breast cancer metastasis as parental regulators of CXCR4(+) mCSCs, and highlight the therapeutic requisite of targeting iCSCs, but not CXCR4(+) mCSCs, to restrain breast cancer metastasis from the root by inhibiting the generation of mCSCs from iCSCs. Considering the pivotal role of iCSCs in tumor metastasis, the possibility of metastasis to be a 'stem cell phenomena' is suggested.

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The nuclear factor κB (NF-κB) is a superfamily of transcription factors. It plays an important role in development & progression of cancer. This study was conducted in a tertiary care centre to investigate the significance of NF-κB as a prognostic marker in breast cancer and study its relation with established prognostic markers such as tumor grade, lymph node status, hormone receptor & HER-2/neu expression. We measured NF-κB expression of breast cancer tissue as a test sample & from fibroadenoma as a control. Measurement was done by Western Blot Technique using p65 protein of NF-κB super family of transcription factors. ER,PR and HER-2/neu were measured by immunohistochemistry methods. NF-κB/p65 is significantly associated with large tumor size (≥5 cm), high grade tumors, negative ER, negative PR, positive HER-2/neu and high NPI (≥5.4) scores. NF-κB/p65 expression implies aggressive biological behaviour of breast cancer & this study validates significant association of NF-κB /p65 overexpression with large tumor size, negative estrogen & progesterone receptor status and overexpression of c-erbB2 oncoprotein.

Transplantation of adipose-derived stem cells (ADSCs) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ADSCs are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned medium (CM) and concentrated to prepare a therapeutic factor concentrate (TFC) composed of a cocktail of beneficial growth factors and cytokines that individually and in combination demonstrate disease-modifying effects. The ability of a TFC to promote reperfusion in a rabbit model of CLI was evaluated. A total of 27 adult female rabbits underwent surgery to induce ischemia in the left hindlimb. An additional five rabbits served as sham controls. One week after surgery, the ischemic limbs received intramuscular injections of either (1) placebo (control medium), (2) a low dose of TFC, or (3) a high dose of TFC. Limb perfusion was serially assessed with a Doppler probe. Blood samples were analyzed for growth factors and cytokines. Tissue was harvested postmortem on day 35 and assessed for capillary density by immunohistochemistry. At 1 month after treatment, tissue perfusion in ischemic limbs treated with a high dose of TFC was almost double (p < 0.05) that of the placebo group [58.8 ± 23 relative perfusion units (RPU) vs. 30.7 ± 13.6 RPU; mean ± SD]. This effect was correlated with greater capillary density in the affected tissues and with transiently higher serum levels of the angiogenic and prosurvival factors vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). The conclusions from this study are that a single bolus administration of TFC demonstrated robust effects for promoting tissue reperfusion in a rabbit model of CLI and that a possible mechanism of revascularization was promotion of angiogenesis by TFC. Results of this study demonstrate that TFC represents a potent therapeutic cocktail for patients with CLI, many of whom are at risk for amputation of the affected limb.

Purpose:This study aims to compare the various distraction methods used during office cystoscopy to decrease pain and dissatisfaction among patients.Materials and Methods:Two hundred patients undergoing rigid cystoscopy between January 2017 and July 2017 were randomized into four groups of 50 patients: (1) Group I: Patients who listened to music during the cystoscopy, (2) Group II: Patients allowed real-time visualization of the cystoscopy, (3) Group III: Patients who listened to music and had real-time visualization of the procedure, (4) Group IV: Control group undergoing cystoscopy without any distraction used. A visual analog scale (VAS) (1–10) was used for a self-assessment of pain, satisfaction, and willingness for repeat cystoscopy.Results:Demographic characteristics, mean age, procedure duration, and procedure indications were statistically similar between the four groups. The mean VAS pain score were significantly lower in the three study Groups (I, II, and III) where distraction methods were used during cystoscopies as compared to the control Group IV (P < 0.001) and the satisfaction VAS scores and VAS scores for willingness to undergo a repeat procedure were significantly higher in the study groups (P < 0.001). Statistically significant decreased postprocedural pulse rate and blood pressure in comparison with to their preprocedural values were observed when distraction methods were used (P < 0.01). Patients undergoing cystoscopies listening to music and real-time visualization (Group III) had better VAS scores than the others (P < 0.01).Conclusions:Distraction methods reduce pain and increase satisfaction among patients. Best results are with combined listening to music and direct real-time visualization.

Malignant melanoma (MM) urgently needs identification of new markers with better predictive value than currently-used clinical and histological parameters. Cancer cells stimulate the formation of a specialized tumor microenvironment, which reciprocally affects uncontrolled proliferation and migration. However, this microenvironment is heterogeneous with different sub-compartments defined by their access to oxygen and nutrients. This study evaluated microvascular density (MVD), CD3+ lymphocytes (TILs) and FOXP3+ T-regulatory lymphocytes (Tregs) on formalin-fixed paraffin-embedded tissue sections using light microscopy. We analyzed 82 malignant melanomas, divided according to the AJCC TNM classification into four groups—pT1 (35), pT2 (17), pT3 (18) and pT4 (12)—and 25 benign pigmented nevi. All parameters were measured in both the central areas of tumors (C) and at their periphery (P). A marked increase in all parameters was found in melanomas compared to nevi (p = 0.0001). There was a positive correlation between MVD, TILs, FOXP3+ Tregs and the vertical growth phase. The results show that MVD, TILs and FOXP3+ Tregs substantially influence cutaneous melanoma microenvironment. We found significant topographic differences of the parameters between central areas of tumors and their boundaries.