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Introduction: Better treatments for ovarian cancer are needed to eliminate residual peritoneal disease after initial debulking surgery. The present study evaluated Trastuzumab to deliver Pb-214/Bi-214 for targeted alpha therapy (TAT) for HER2-positive ovarian cancer in mouse models of residual disease. This study is the first report of TAT using a novel Radon-222 generator to produce short-lived Lead-214 (Pb-214, t1/2 = 26.8 min) in equilibrium with its daughter Bismuth-214 (Bi-214, t1/2 = 19.7 min); referred to as Pb-214/Bi-214. In this study, Pb-214/Bi-214-TCMC-Trastuzumab was tested.Methods: Trastuzumab and control IgG antibody were conjugated with TCMC chelator and radiolabeled with Pb-214/Bi-214 to yield Pb-214/Bi-214-TCMC-Trastuzumab and Pb-214/Bi-214-TCMC-IgG1. The decay of Pb-214/Bi-214 yielded α-particles for TAT. SKOV3 and OVAR3 human ovarian cancer cell lines were tested for HER2 levels. The effects of Pb-214/Bi-214-TCMC-Trastuzumab and appropriate controls were compared using clonogenic assays and in mice bearing peritoneal SKOV3 or OVCAR3 tumors. Mice control groups included untreated, Pb-214/Bi-214-TCMC-IgG1, and Trastuzumab only.Results and discussion: SKOV3 cells had 590,000 ± 5,500 HER2 receptors/cell compared with OVCAR3 cells at 7,900 ± 770. In vitro clonogenic assays with SKOV3 cells showed significantly reduced colony formation after Pb-214/Bi-214-TCMC-Trastuzumab treatment compared with controls. Nude mice bearing luciferase-positive SKOV3 or OVCAR3 tumors were treated with Pb-214/Bi-214-TCMC-Trastuzumab or appropriate controls. Two 0.74 MBq doses of Pb-214/Bi-214-TCMC-Trastuzumab significantly suppressed the growth of SKOV3 tumors for 60 days, without toxicity, compared with three control groups (untreated, Pb-214/Bi-214-TCMC-IgG1, or Trastuzumab only). Mice-bearing OVCAR3 tumors had effective therapy without toxicity with two 0.74 MBq doses of Pb-214/Bi-214-TCMC-trastuzumab or Pb-214/Bi-214-TCMC-IgG1. Together, these data indicated that Pb-214/Bi-214 from a Rn-222 generator system was successfully applied for TAT. Pb-214/Bi-214-TCMC-Trastuzumab was effective to treat mouse xenograft models. Advantages of Pb-214/Bi-214 from the novel generator systems include high purity, short half-life for fractioned therapy, and hourly availability from the Rn-222 generator system. This platform technology can be applied for a variety of cancer treatment strategies.

Verrucous Haemangioma (VH) is a rare, congenital vascular malformation of cutaneous and subcutaneous tissue. It usually presents as macular lesion at birth which progresses with age, and may become bluish papules, nodules, and warty plaques. Linear presentation of this disease is even rarer. Here the present case report presents a case of a 30-year-old male patient with multiple raised erythematous hyperkeratotic papules and plaques over right forearm since birth which was arranged in a linear pattern.The patient also had asymptomatic papules on right thigh and lower back region, associated with sensory loss and peripheral nerve thickening. Dermoscopy of forearm showed reddish-blue lacunae, alveolar pattern, and whitish veils. Colour Doppler showed intradermal dilated venous channels with thrombosis which was suggestive of haemangioma. Histopathological examination confirmed the diagnosis of linear VH on forearm and slit skin Ziehl-Neelsen staining was suggestive of histoid leprosy. Linear VH is a rare congenital venous malformation, progresses proportionately with age. Dermoscopy can help in early diagnosis of vascular lesions. Complete surgical excision is the treatment of choice.

Eruptive collagenomas are rare nonfamilial connective tissue nevi of unknown etiology and pathogenesis, which are characterized by an abrupt onset of asymptomatic papules, nodules, and plaques on the trunk and extremities. Herein, we report a unique case of eruptive collagenoma in a 29-year-old female, who presented with multiple asymptomatic skin-colored to slightly hyperpigmented papules over the anterolateral aspect of the neck with no systemic involvement. Family history was unremarkable, and the diagnosis was confirmed by histopathological examination which showed thickened homogenized collagen bundles in the superficial dermis. We report this case due to the paucity of cases in Indian literature on eruptive collagenoma in a young female with only neck involvement.

Intravascularly administered radiation therapy using beta (β-)-emitting radioisotopes has relied on either intravenously injected radiolabeled peptides that target cancer or radiolabeled microspheres that are trapped in the tumor following intra-arterial delivery. More recently, targeted intravenous radiopeptide therapies have explored the use of alpha (α)-particle emitting radioisotopes, but microspheres radiolabeled with α-particle emitters have not yet been studied. Here, FDA-approved macroaggregated albumin (MAA) particles were radiolabeled with Bismuth-212 (Bi-212-MAA) and evaluated using clonogenic and survival assays in vitro and using immune-competent mouse models of breast cancer. The in vivo biodistribution of Bi-212-MAA was investigated in Balb/c and C57BL/6 mice with 4T1 and EO771 orthotopic breast tumors, respectively. The same orthotopic breast cancer models were used to evaluate the treatment efficacy of Bi-212-MAA. Our results showed that macroaggregated albumin can be stably radiolabeled with Bi-212 and that Bi-212-MAA can deliver significant radiation therapy to reduce the growth and clonogenic potential of 4T1 and EO771 cells in vitro. Additionally, Bi-212-MAA treatment upregulated γH2AX and cleaved Caspase-3 expression in 4T1 cells. Biodistribution analyses showed 87–93% of the Bi-212-MAA remained in 4T1 and EO771 tumors 2 and 4 h after injection. Following single-tumor treatments with Bi-212-MAA there was a significant reduction in the growth of both 4T1 and EO771 breast tumors over the 18-day monitoring period. Overall, these findings showed that Bi-212-MAA was stably radiolabeled and inhibited breast cancer growth. Bi-212-MAA is an exciting platform to study α-particle therapy and will be easily translatable to larger animal models and human clinical trials.

Objectives: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease of unknown etiology, mainly affecting female of child-bearing age group. Clinical scenario of SLE is not well defined in east region of India, especially in tribal region of Jharkhand. This article is mainly focused on clinical and laboratory characteristics of SLE in tribal region of Jharkhand. Materials and Methods: This was an analytical cross-sectional single-centered study conducted at RIMS, Ranchi, a tertiary care center of Jharkhand, between November 2020 and October 2021. A total 50 patients were diagnosed as SLE based on Systemic Lupus International Collaborating Clinics criteria. Results: Forty-five (90%) of patients in our study were female, with female to male ratio of 9:1. The mean age of presentation was 26.78 ± 8.12. Constitutional symptoms were found in 96% of patients, followed by anemia in 90% of patients. Renal involvement was found in 74% of patients, followed by polyarthritis (72%), malar rash (60%), and neurological manifestations (40%). Anti-nuclear antibody, anti-dsDNA, and anti-Smith antibodies were found positive in 100%, 84%, and 80% of patients, respectively. Conclusions: Clinical characteristics of SLE as per our study would help the health care professionals in this region to identify the disease at early stage and initiate appropriate treatment.

Abstract Melanoma originates from melanin-producing cells called melanocytes. Melanoma poses a great risk because of its rapid ability to spread and invade new organs. Cellular metastasis involves alteration in the gene expression profile and their transformation from epithelial to mesenchymal state. Despite of several advances, metastatic melanoma being a key cause of therapy failure and mortality remains poorly understood. p32 has been found to be involved in various physiological and pathophysiological conditions. However, the role of p32 in melanoma progression and metastasis remains underexplored. Here, we identify the role of p32 in the malignancy of both murine and human melanoma. p32 knockdown leads to reduced cell proliferation, migration, and invasion in murine and human melanoma cells. Furthermore, p32 promotes in vitro tumorigenesis, inducing oncogenes and EMT markers. Mechanistically, we show p32 regulates tumorigenic and metastatic properties through the Akt/PKB signaling pathway in both murine and human melanoma. Furthermore, p32 silencing attenuates melanoma tumor progression and lung metastasis in vivo, modulating the tumor microenvironment by inhibiting the angiogenesis, infiltration of macrophages, and leukocytes in mice. Taken together, our findings identify that p32 drives melanoma progression, metastasis, and regulates the tumor microenvironment. p32 can be a target of a novel therapeutic approach in the regulation of melanoma progression and metastasis.

Abstract Background Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules. Results In this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them. Conclusions With this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.

Abstract Background Receptor for advanced glycation end products (RAGE) is a multi-ligand transmembrane receptor of the immunoglobulin superfamily. Lysophosphatidic acid (LPA) is a ligand for RAGE and is involved in physiological and pathophysiological conditions including cancer. However, RAGE-LPA axis is unexplored in lung and mammary cancer. Methods RAGE was silenced in A549, MDA MB-231 and MCF7 using RAGE shRNA. For in vitro tumorigenesis, we performed wound healing, colony formation, cell proliferation and invasion assays. Evaluation of expression of oncogenes, EMT markers and downstream signaling molecules was done by using western blot and immunohistochemistry. For subcellular expression of RAGE, immunofluorescence was done. In vivo tumorigenesis was assessed by intraperitoneal injection of cancer cells in nude mice. Results Here we show RAGE mediated profound increase in proliferation, migration and invasion of lung and mammary cancer cells via LPA in Protein kinase B (PKB) dependent manner. LPA mediated EMT transition is regulated by RAGE. In vivo xenograft results show significance of RAGE in LPA mediated lung and mammary tumor progression, angiogenesis and immune cell infiltration to tumor microenvironment. Conclusion Our results establish the significance and involvement of RAGE in LPA mediated lung and mammary tumor progression and EMT transition via RAGE. RAGE-LPA axis may be a therapeutic target in lung and mammary cancer treatment strategies. Video Abstract

Acquired port wine stain though an uncommon entity that develops later in life, resembles congenital port wine stain morphologically and histologically. Congenital port wine stains are vascular lesions caused by progressive ectasia of blood vessels which is located in the vascular plexus of the dermis. Congenital port-wine stains may be associated with Sturge Weber syndrome causing neurological and eye abnormalities such as glaucoma. Here we report a 60-year-old male presenting with a complaint of asymptomatic reddish patches over the nose for 15 years.

Intrinsic resistance to ionizing radiation is the major impediment in the treatment and clinical management of esophageal squamous cell carcinoma (ESCC), leading to tumor relapse and poor prognosis. Although several biological and molecular mechanisms are responsible for resistance to radiotherapy in ESCC, the molecule(s) involved in predicting radiotherapy response and prognosis are still lacking, thus requiring a detailed understanding. Recent studies have demonstrated an imperative correlation amongst several long non-coding RNAs and their involvement in complex cellular networks like DNA damage and repair, cell cycle, apoptosis, proliferation, and epithelial-mesenchymal transition. Additionally, accumulating evidence has suggested abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy effects in tumor cells’ sensitivity. Thus, lncRNAs indeed represent unique molecules that can influence tumor cell susceptibility for various clinical interventions. On this note, herein, we have summarized the current status of lncRNAs in augmenting resistance/sensitivity in ESCC against radiotherapy. In addition, we have also discussed various strategies to increase the radiosensitivity in ESCC cells under clinical settings.

Genetic variation and phylogenetic relationships among 76 birds belonging to Indian Red Jungle Fowl (RJF) and three domestic chicken breeds viz. one Indian native sport breed, Aseel (AS) and two global high yielding breeds of egg type, White Leghorn (WL) and meat type, Red Cornish (RC) were evaluated using Amplified Fragment Length Polymorphism (AFLP) markers. A total of 318 scorable dominant AFLP bands in the range of 50-500 bp using 20 EcoRI/TaqI primer combinations were detected across populations. The mean number of polymorphic bands across all four populations was 15.5 per primer combination. Species-specific bands were also found in all populations except WL. Nei’s gene diversity was measured between RJF and domestic chickens and it was significantly higher in RJF population (0.309) as compared to the domestic chicken populations of AS (0.129), WL (0.067) and RC (0.066). RJF showed maximum genetic distance with RC (0.221) and minimum with AS (0.177) population. The divergence between RJF and domestic chicken was observed by constructing an UPGMA dendrogram. RJF was present in one cluster and whereas the three domestic chickens were tightly clustered in another group. This clustering pattern was also confirmed by principal component analysis (PCA). The estimate of genetic identities (GI) and genetic distances (GD) using Nei (1972) also suggest comparatively more closeness of RJF with AS (an Indian native chicken breed) than those of commercial breeds WL and RC. These results support the earlier understanding that chicken was first domesticated for game purpose rather than as food.

Orofacial granulomatosis (OFG) is a rare disorder affecting the orofacial region, and clinically characterized by diffuse, nontender, soft to firm, painless swelling restricted to one or both lips and intraoral sites such as tongue, gingiva and buccal mucosa. Histologically, OFG is characterized by noncaseating granulomatous inflammation. The early diagnosis of OFG is essential for the better prognosis of the lesion. Delay in diagnosis of OFG results into formation of indurated and permanent swelling of the lip that not only compromises esthetic appearance but also causes impairment in function such as speaking and eating. Early diagnosis of OFG is challenging to the health care professionals due to clinical and histological resemblance to other chronic granulomatous disorders. Thus, dentists may act as a first person to diagnose the lesion and play an important role in the multidisciplinary treatment of granulomatous disorders. Here, we present a case of OFG affecting lips and gingiva in a 15-year-old patient without any identifiable systemic or local causes.

Acroangiodermatitis or Pseudo-Kaposi sarcoma is a rare angioproliferative entity, related to chronic venous insufficiency or certain other vascular anomalies. It is often associated with chronic venous insufficiency, arteriovenous malformation of the legs, chronic renal failure treated with dialysis, paralyzed legs and amputation stumps. We hereby describe a case of 45 year old female presenting with pitting pedal edema, multiple ulcers over bilateral lower limbs with irregular margins with erythema and hyperpigmentation of the surrounding skin. Color Doppler study of bilateral lower limbs was normal. Histopathological examination from one of the lesions showed hyperplastic epidermis, proliferation of capillaries in dermis, hemosiderin deposits and lymphocytic infiltrate. These features thus confirmed the diagnosis of Acroangiodermatitis.

Granuloma faciale (GF) is an uncommon, cutaneous disorder characterized by one to several soft, erythematous to livid papules, plaques, or nodules, usually occurring on the face. Extra-facial lesions occur rarely. We present a case report of 33-year-old male who presented with keloidal lesions on face and left shoulder. The patient didn′t respond with intralesional triamcinolone and showed poor response with the addition of topical tacrolimus. Surgical excision in consultation with plastic surgeons is planned.

"Tripe palms" or pachydermatoglyphy is a descriptive term of acanthosis nigricans of the palms and is associated with internal malignancy. It often precedes the diagnosis of a new or recurrent tumor. Malignant acanthosis nigricans is most commonly associated with intra-abdominal malignancies. In patients with both tripe palms and acanthosis nigricans, gastric carcinoma is the most common followed by lung carcinoma. There are very few reports in the literature of malignant acanthosis nigricans associated with gynecological malignancies. We report this case because of its rarity. A 47-year-old lady presented with lower abdominal swelling and progressive hyperpigmentation which preceded the abdominal swelling by 6 months. On investigations, she was found to have ovarian cancer. The presence of acanthosis nigricans in conjunction with tripe palms in a female patient is highly suggestive of an internal malignancy including an ovarian cancer and demands an extensive search for the hidden ovarian cancer.

Incidence of pitting, vary considerably in different types of psoriasis. In clinical practice, toe nail examination is inconvenient. There are inadequate studies which show relation of nail pitting with duration and severity of the disease. The objective was to examine the incidence of finger nail pitting in all types of cutaneous psoriasis and its relation with different variables. This is a clinico-epidemiological study. A careful clinical examination of finger nails was done in day time. Severity of disease was calculated by psoriasis area severity index (PASI). Statistical analysis was done using Microcomputer statistics software (MSTAT). In study group, 621 patients and in control group 350 people were taken. Finger nail pitting was present in 37% (total number was < 20 in 17%; 20-60 in 8% and > 60 in 12%) in study group. In control group, it was present in 10% (in all cases total number was < 20). In < 1 year duration group, pitting was present in 32% of cases, while in > 1 year duration group it was 40.5%.In mild psoriasis, pitting was present in 34.2%, while in severe cases it was 47.6%. Finger nail pitting is an important nail finding in psoriasis and its incidence increases with duration and severity of disease.

A 55-year-old male presented with recurrent crops of crusted papular lesions and boils over buttocks for 1month along with a short history of productive cough. The diagnosis of papulonecrotictuberculid (PNT) with pulmonary tuberculosis was made based on history, clinical features, laboratory investigations, and response to antitubercular treatment.

Objective To examine the prevalence of itching in psoriatic skin lesions and its relation with different variables. Patients and methods A simple questionnaire and a verbal 4-point intensity scale were used. Severity of disease was calculated by using Psoriasis Area Severity Index (PASI). Results Six hundred and fourteen patients of psoriasis were examined in which majority were chronic plaque type. Pruritus was present in 79% of the patients, and was severe in 34%; moderate in 15% and mild in 30%. Conclusion Pruritus was common in chronic plaque psoriasis, female patients and those with more severe disease. Itching was more severe in more severe type of psoriasis. It was more common in females in comparison to males. But there was no difference between pediatric and adult psoriasis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a patient with asymptomatic moduloulcerative lesion on the right pre-auricular area that started as a small nodule and increased in size as it became ulcerated. The patient had a history of similar lesions twice in a span of three years which had been previously excised. Histopathological findings suggests the presence of epithelial neoplasm ad is well-circumscribed and connected with surface epidermis at multiple points.

Arsenicosis is a multisystem disorder, with many cutaneous features. The cutaneous manifestations take the form of pigmentary changes, hyperkeratosis, and skin cancers (Bowen's disease, squamous cell carcinoma, and basal cell carcinoma). It is a known carcinogen and there is association between chronic arsenic exposure and malignancy of bladder, lung, liver, kidney and other visceral malignancies. Our patient came from an endemic area where levels of arsenic are high in drinking water and had features of arsenical keratosis for past fifteen years along with metastatic testicular cancer at the time of presentation. Arsenic exposure may increase the risk of testicular cancer. [ABSTRACT FROM AUTHOR]

The article discusses the symptoms and condition of the multiple umbilicated papulonodular lesions skin disorder. It cites the case of a 50-year-old woman presented with multiple papulonodular lesions on the face, neck, and upper back. It also mentions the examination undergone by the patient in which the initial diagnosis was cutaneous histoplasmosis, which responds to itraconazole, fluconazole or amphotericin B treatments.