Synthesis of steroidal dihydropyrazole derivatives using green ZnO NPs and evaluation of their anticancer and antioxidant activity.

Zinc oxide nanoparticles (ZnO NPs) were synthesized by a green method using Azadirachta indica leaf extract. The structure of the prepared ZnO (NPs) were characterized by FT-IR, XRD, SEM-EDX and TEM analyses. The biosynthesized ZnO (NPs) were then used as a catalyst for the synthesis of steroidal dihydropyrazole derivatives through a one-pot multicomponent reaction involving phenyl acetylene and hydrazine derivatives. The anticancer activity of newly synthesized compounds were evaluated against three cancer cell lines namely HeLa (human cervical carcinoma), Hep3B (human hepatocellular carcinoma) and MCF7 (human breast adenocarcinoma) by MTT assay. The tested compounds were found to be active against all cancer cell lines and less toxic towards normal peripheral blood mononuclear cells (PBMCs). Antioxidant activity have also been investigated via free radical scavenging ability using DPPH, FRAP and ABTS assay. The tested compounds were found to exhibit moderate to good antioxidant activity which increases with increase in the concentration of steroidal dihydropyrazoles. Among all the tested steroidal dihydropyrazoles, compound 17 is found to be most active.

Exosome-encapsulated ncRNAs: Emerging yin and yang of tumor hallmarks.

Tumorigenesis is a multifaceted process, where multiple physiological traits serving as cancer's distinctive characteristics are acquired. "Hallmarks of cancer" is a set of cognitive abilities acquired by human cells that are pivotal to their tumor-forming potential. With limited or no protein-coding ability, non-coding RNAs (ncRNAs) interact with their target molecules and yield significant regulatory effects on several cell cycle processes. They play a "yin" and "yang" role, thereby functioning both as oncogenic and tumor suppressor and considered important in the management of various types of cancer entities. ncRNAs serve as important post-transcriptional and translational regulators of not only unrestricted expansion and metastasis of tumor cells but also of various biological processes, such as genomic mutation, DNA damage, immune escape, and metabolic disorder. Dynamical attributes such as increased proliferative signaling, migration, invasion, and epithelial-mesenchymal transition are considered to be significant determinants of tumor malignancy, metastatic dissemination, and therapeutic resistance. Furthermore, these biological attributes engage tumor cells with immune cells within the tumor microenvironment to promote tumor formation. We elaborate the interaction of ncRNAs with various factors in order to regulate cancer intra/intercellular signaling in a specific tumor microenvironment, which facilitates the cancer cells in acquiring malignant hallmarks. Exosomes represent a means of intercellular communication and participate in the maintenance of the tumor hallmarks, adding depth to the intricate, multifactorial character of malignant neoplasia. To summarize, ncRNAs have a profound impact on tumors, affecting their microcirculation, invasiveness, altered metabolism, microenvironment, and the capacity to modify the host immunological environment. Though the significance of ncRNAs in crosstalk between the tumor and its microenvironment is being extensively explored, we intend to review the hallmarks in the light of exosome-derived non-coding RNAs and their impact on the tumor microenvironment.

Immunotherapy With 5, 15-DPP Mediates Macrophage M1 Polarization and Modulates Subsequent Mycobacterium tuberculosis Infectivity in rBCG30 Immunized Mice.

Tuberculosis (TB) is a significant and continuing problem worldwide, with a death toll of around 1.5 million human lives annually. BCG, the only vaccine against TB, offers a varied degree of protection among human subjects in different regions and races of the world. The majority of the population living near the tropics carries a varying degree of tolerance against BCG due to the widespread prevalence of non-tuberculous mycobacteria (NTM). Interestingly, ≈90% of the Mycobacterium tuberculosis (Mtb) infected population restrain the bacilli on its own, which strengthens the notion of empowering the host immune system to advance the protective efficacy of existing mycobacterial vaccines. In general, Mtb modulates IL-10/STAT3 signaling to skew host mononuclear phagocytes toward an alternatively activated, anti-inflammatory state that helps it thrive against hostile immune advances. We hypothesized that modulating the IL-10/STAT3 driven anti-inflammatory effects in mononuclear cells may improve the prophylactic ability of TB vaccines. This study investigated the immunotherapeutic ability of a porphyrin based small molecule inhibitor of IL-10/STAT3 axis, 5, 15-diphenyl porphyrin (DPP), in improving anti-TB immunity offered by second generation recombinant BCG30 (rBCG30-ARMF-II®) vaccine in mice. The DPP therapy potentiated vaccine induced anti-TB immunity by down-modulating anti-inflammatory responses, while simultaneously up-regulating pro-inflammatory immune effector responses in the immunized host. The employed DPP based immunotherapy led to the predominant activation/proliferation of pro-inflammatory monocytes/macrophages/DCs, the concerted expansion of CD4+/CD8+ effector and central memory T cells, alongside balanced Th17 and Treg cell amplification, and conferred augmented resistance to aerosol Mtb challenge in rBCG30 immunized BALB/c mice.

Cytohistomorphological grading of breast carcinoma with special reference to apoptotic rates and lymph node metastasis.

To analyze the significance of comparative evaluation of cytohistomorphological grading of infiltrating ductal carcinoma with specific reference to lymphnode metastasis status and apoptotic index. 50 patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were included in the study. Concordance between cytological and histological grades was calculated. Cytological smears were also evaluated for apoptotic rates and lymph node metastasis and then compared with the histological grades using regression analysis. Histological and cytological grades were comparable and statistically significant difference was found in the lymphnode metastasis rate and apoptotic index in the three cytological grades of the tumor. Moreover, by considering the apoptotic rates, the sensitivity of cytological grading significantly rose in relation to histological grade. With histological grade taken as the standard, cytology was found to be comparable but less sensitive for grading infiltrating ductal carcinoma. However, by considering lymphnode status and apoptotic rates as calculated on cytology, the sensitivity of cytological grading rose significantly in relation to histological grade. Therefore, apoptotic index incorporated with cytological grade may provide relevant information on the aggressiveness of invasive ductal carcinoma of breast and could be a useful parameter to take into consideration when selecting neo-adjuvant therapy.

Giant primary mesenteric liposarcoma: a rare case report.

Primary mesenteric liposarcoma is a rare malignant tumor of mesenchymal origin. These tumors are often found to be of substantial size upon first clinical presentation. We report a case of primary mesenteric liposarcoma in a 55 year old man who underwent laparotomy for the clinical/radiological impression of a mesenteric cyst. FNAC was inconclusive due to suboptimal cellularity. On laparotomy there were 2 masses (diameter- 19 and 14 cms) weighing approximately 8.5 kilograms together. Histopathology showed features of atypical lipomatous tumor / well differentiated liposarcoma (ALT/WDLS) with mixed histological pattern (e.g. lipoma like, sclerosing and myxoid areas) varying from area to area. Prognosis of ALT/WD liposarcoma depends upon its anatomic location and most aggressive histological subtype. This case is being presented because of its huge dimensions, rarity of the site and mixed histological pattern.

Nanoparticle-Based Mycosis Vaccine.

Many diseases that were considered major affliction of mankind in the past have been successfully eradicated with introduction of appropriate vaccine strategies. In order to expedite new challenges coming up to deal with various infectious diseases, nano-particulate-based subunit vaccines seem to be the demand of ordeal. The nano-vaccines can find better scope for the diseases that were not rampant in the semi-advanced world few years back. For example in present-day circumstances that corroborate with advancement in the field of medical sciences in terms of cancer chemotherapy, organ transplantation, therapy of autoimmune diseases, etc.; along with prevalence of altogether unheard diseases such as HIV infection, people are at risk of infliction with many more pathogens. In this regard, development of an effective prophylactic strategy against many opportunistic infections primarily caused by fungal pathogens needs better understanding of host pathogen relation and role of active immunity against pathogenic fungi. In the present study, we have tried to decipher effectiveness of a nano-sized vaccine delivery system in imparting protection against fungal pathogens.

Significance of AgNOR score in benign and malignant soft tissue tumours.

AgNOR staining was employed on FNAC and histopathological sections obtained from patients with soft tissue tumours. The study comprised of 20 normal appearing soft tissues, 74 benign and 36 malignant soft tissue tumours. The slides were stained with AgNOR in order to differentiate between benign and malignant soft tissue tumours. The mean AgNOR count in normal appearing soft tissues, benign lesions and malignant lesions was 1.04+/-0.10 (0.94-1.14), 1.51+/-0.21 (1.1-2.1) and 4.96+/-1.33 (2.57-7.21) respectively. The mean AgNOR count was found to be higher in benign soft tissue tumours as compared to normal appearing soft tissues and the difference was found to be statistically significant. The mean AgNOR count in soft tissue sarcomas was found to be higher as compared to both normal appearing soft tissues and benign soft tissue tumours and the results were found to be statistically significant. The increased AgNOR score in both benign and malignant soft tissue tumours as compared to normal appearing soft tissues indicates high proliferative activity. Thus AgNOR staining is a simple and useful method for estimating tumour cell proliferation thereby differentiating normal appearing soft tissues from benign and malignant soft tissue tumours.

Disseminated cryptococcosis in an immunocompetent child.

Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals. Disseminated cryptococcal infection is very rare and almost always found to occur in immunocompromised individuals especially in persons infected with HIV. This is particularly attributed to its capsulated spores. But there are few reported cases in which it has been found to cause disseminated infections even in immunocompetent individuals. We report a similar case of disseminated cryptococcal infection in an immunocompetent host. Early detection and treatment of disseminated cryptococcosis is essential to reduce morbidity and for better outcome.

Laryngeal histoplasmosis.

Histoplasmosis is a fungal infection, having interesting synonyms such as Cave disease, Darling's disease, Ohio Valley disease, reticuloendotheliosis, Spelunker's lung and Caver's disease. The aetiological agent is a dimorphic fungus, Histoplasma capsulatum, causing chronic granulomatous disease. The route of transmission is by inhalation of dust particles from soil contaminated by excrement of birds or bats, harbouring the small spores or microconidia, which is considered the infectious form of fungus. The spectrum of illness ranges from subclinical infection of the lung to progressive disseminated disease. The major bulk of histoplasmosis infections are asymptomatic or present with mild influenza like illness and involve immunocompetent individuals. However, the immunocompromised or immunodeficient cases have disseminated/haematogenous infections with multiple organs involved and are usually fatal unless treated immediately. Laryngeal involvement is associated with the disseminated form of the disease. Histoplasmosis of larynx is a rare entity and poses diagnostic difficulty to otolaryngologists because clinically it may be mistaken for malignancy. We report an unusual case of laryngeal histoplasmosis in a man aged 60 years who presented with provisional diagnosis of tuberculosis/malignancy.

Significance of apoptosis in prostatic intraepithelial neoplasia and carcinoma.

This study was carried out to assess the significance of apoptosis in prostatic intraepithelial neoplasia (PIN) and prostate cancer. A total of 120 prostatic specimens were studied in the department of Pathology [corrected] JNMC, Aligarh. The rate of apoptosis in PIN and prostate cancer was examined by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on haematoxylin and eosin stained histological sections [corrected] A significant correlation was noted between increasing apoptotic indices and increasing Gleason grades within a cancer.

Spindle-cell ameloblastic carcinoma of the maxilla with adenoid cystic carcinoma-like areas: A new variant?

Ameloblastic carcinoma is a rare aggressive malignancy of odontogenic epithelial origin. The disease has been reported to afflict people over a wide range of age group without any sex predilection. It is characterized by rapid growth and destruction of overlying bones along with involvement of adjacent soft tissues. The overall prognosis of this cancer is poor despite radical surgery and radiotherapy. Owing to the rarity of this lesion, complete data on the biological behavior and response to different treatment modalities are still lacking. The authors hereby report a case of this uncommon tumor arising from left maxilla in a 60-year-old Indian male. Histopathological examination of the tumor showed foci of spindling intermixed with large areas of tumor cells arranged in cribriform pattern and having luminal eosinophilic material which was reminiscent of adenoid cystic carcinoma. A final diagnosis was achieved after immunohistochemical study. These unusual findings prompted this case report.

Cytodiagnosis of yolk sac tumor.

To analyze cytomorphologic features of yolk sac tumors of childhood. Four cases of pediatric yolk sac tumor (YST), diagnosed by fine needle aspiration cytology were reviewed (1998-2002). Age of patients ranged from 1(1/2) to 5 years. Three cases presented clinically with an intra-abdominal mass while one case presented with a testicular mass. Fine needle aspirates had been obtained directly as well as under radiologic (USG/CT) guidance. Smears were stained with H & E and Papanicolaou stain. In all cases values of serum alpha-fetoprotein and hCG were available preoperatively. Histopathologic diagnosis was correlated with cytologic findings in all the cases. Cytologic examination showed richly cellular smears with a combination of morphological patterns. Characteristically, tumor cells were arranged in papillary groups, tight cell clusters and formed acinar structures. Cells showed enlarged, moderately pleomorphic, hyperchromatic nuclei and moderate amount of cytoplasm, some of which displayed cytoplasmic vacuolation, displacing the nuclei eccentrically. Preoperatively, serum alpha-fetoprotein level was raised in all cases. Histopathology confirmed the cytologic diagnosis. Yolk sac tumor is common among the germ cell tumors of pediatric age group which presents a spectrum of cytomorphologic features having important differences with other germ cell neoplasm, e.g. embryonal carcinoma. Clinicoradiologic features and tumor markers are additionally helpful for an accurate cytologic diagnosis.

Retinal tissue in mature cystic teratoma of ovary presenting with full-term pregnancy.

Mature cystic teratomas are benign ovarian neoplasms which account for around 95% of all ovarian germ cell tumours and contain tissues derived from two or three embryonic germ layers. These tumours are frequently diagnosed in women of reproductive age group and can result in fetomaternal distress if concurrent pregnancy occurs. The authors describe a case of successful natural pregnancy in a 30-year-old woman with coexisting mature cystic teratoma of ovary that culminated in viable childbirth at term. Subsequent histopathological examination of the tumour revealed a mature teratoma composed predominantly of ectodermal elements along with retinal tissues--a rare finding that prompted this case report.

Role of fine needle aspiration, imprint and scrape cytology in the evaluation of intraoral lesions.

AIM: The primary goal of our study was to evaluate the value and accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of various intraoral lesions and to correlate the cytological diagnosis with final histopathological findings. MATERIALS AND METHODS: Fine needle aspiration was performed in 229 patients presented with different lesions of the oral cavity at our institution. Cytological findings were then compared with final histopathological diagnosis. RESULTS: With a male to female ratio of 1.79:1, 229 patients presented with different lesions of the oral cavity were aspirated. Histopathological correlation was available in 86.9% of cases while inadequate material was obtained in 13.1% cases. The diagnostic accuracy of fine needle aspiration in diagnosing benign, pre-malignant and malignant lesions were 95.8%, 84.6% and 97% respectively. Overall the diagnostic accuracy of FNAC in diagnosing intraoral lesions was 94.9% with sensitivity and specificity of 93.2% and 96.8% respectively. CONCLUSION: FNAC of intraoral lesion is recommended as a valuable procedure for the initial evaluation of all intraoral lesions as it is simple, inexpensive, convenient and comfortable to the patient. Moreover, it can offer a rapid and accurate diagnosis for further management of the patient.

Benign mediastinal teratoma with intrapulmonary and bronchial rupture presenting with recurrent hemoptysis.

Mediastinal teratomas are usually asymptomatic tumors, located most commonly in the anterior mediastinum. Very rarely, such tumors may rupture into the tracheobronchial tree, lung, pleura or pericardium. Computed Tomography (CT) is helpful in the diagnosis and differentiation of ruptured and unruptured tumors. We report a case of ruptured anterior mediastinal teratoma in a 20-year-old female presenting with recurrent hemoptysis and cough; thus, mimicking a lung malignancy or tuberculosis. CT demonstrated a heterogeneous fat containing lesion in the anterior mediastinum with extension into the lingular lobe. Subsequent fine needle aspiration cytology (FNAC) yielded plenty of anucleate squames and debris, and a clear cut diagnosis could not be made. Total excision of the tumor was performed and histopathology of the surgically excised mass confirmed the CT diagnosis.

A case of pure endophytic squamous cell carcinoma of the gallbladder: a rare entity with aggressive behaviour.

Pure squamous cell carcinoma of gallbladder is a rare tumor accounting for only 3% of the malignancies of gallbladder. A 35-year-old female presented with pain and lump in right hypochondrium. Ultrasonography and computed tomography revealed a thickened gallbladder filled with stones without any obvious growth and a large hepatic mass. Histologically, a pure type of well differentiated squamous cell carcinoma of gallbladder was diagnosed after excluding all possible differential diagnoses owing to different histogenesis and aggressive biological behaviour. Early diagnosis is the most important parameter for improving the survival indices among the patients with squamous cell carcinoma of the gallbladder.

Role of imprint cytology in the intraoperative diagnosis of pituitary adenomas.

The cytologic touch imprint alone can be diagnostic of pituitary adenomas and meningiomas, etc. A 45-year-old man was operated upon for intracranial meningioma. Imprint cytology revealed distinct cytologic features which helped arriving at the specific diagnosis of pituitary adenoma intraoperatively. Subsequent histopathology and immuno-histochemistry confirmed the diagnosis. Thus intraoperative touch preparations are of immense help in arriving at a diagnosis as well as in excluding other possible differential diagnoses and therefore can replace frozen section for intraoperative consultations of sellar and parasellar tumors.

Eumycetoma versus actinomycetoma: Diagnosis on cytology.

Eumycetoma is a chronic cutaneous and subcutaneous infection caused by various genera of fungi producing specific colored granules known as grains. A 45-year-old farmer presented clinically with a left foot mass with multiple discharging sinuses existing for last 3 years. Clinical and radiological findings suggested a diagnosis of chronic osteomyelitis with suspicion of tuberculosis. Imprints plus fine needle aspiration cytology (FNAC) smears exhibited distinct brown-black colonies of a fungus having branching and septate hyphae embedded in matrix like material against a mixed inflammatory background. Periodic acid Schiff (PAS) stain gave positive staining and subsequent fungal culture confirmed the cytological diagnosis and aided in species identification as Madurella mycetomatis. Thus, eumycetoma can precisely be diagnosed and confidently differentiated from similar conditions such as actinomycetoma by simple and inexpensive cytological techniques such as FNAC and imprint smears, employing routine May-Grünwald-Giemsa, Papanicolaou and simple PAS stains on cytological specimen, thus leading to rapid diagnosis for institution of correct treatment.